Muscle Invasive Bladder Cancer Articles

Articles

  • A Feasibility Study of Durvalumab (MEDI4736) Alone or in Combination With Oleclumab (MEDI9447) as Neoadjuvant Therapy for Muscle-invasive Bladder Cancer (BLASST-2)

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    A Feasibility Study of Durvalumab (MEDI4736) Alone or in Combination With Oleclumab (MEDI9447) as Neoadjuvant Therapy for Muscle-invasive Bladder Cancer (BLASST-2)


    Condition: Muscle Invasive Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03773666

    Sponsor: Dana-Farber Cancer Institute

    Phase: Phase 1

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • For inclusion in the study patients must fulfil all of the following criteria: Written informed consent and any locally-required authorization (e.g. HIPAA) obtained from the patient prior to performing any protocol-related procedures, including screening evaluations
    • Age > 18 years at time of study entry
    • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (See Appendix A).
    • Histologically confirmed bladder transitional cell carcinoma (TCC) ---Patients with mixed histology are required to have a component of TCC, and no component of small cell histology
    • T2-T4a N0 M0 disease, considered appropriate and planned for radical cystectomy
    • Ineligible for cisplatin-based chemotherapy, defined by any of the following:
    • Creatinine clearance (CL) <60 mL/min. GFR should be calculated from serum/plasma creatinine using the Cockcroft-gault formula.
    • CTCAE v5.0 Grade > 1 hearing loss
    • CTCAE v5.0 Grade > 1 neuropathy
    • NYHA Class > II cardiac dysfunction
    • Patients not meeting the above criteria are eligible if she/he declines perioperative cisplatin-based chemotherapy after specific informed consent describing the known benefits of cisplatin-based chemotherapy.
    • Adequate organ function laboratory values as defined below:
    • Hemoglobin ≥ 9.0 g/dL
    • Absolute neutrophil count (ANC) 1.5 x (> 1500 per mm3)
    • Platelet count ≥100 x 109/L (>75,000 per mm3)
    • Albumin > 2.5 g/dL
    • International Normalized Ratio (INR) or activated partial thromboplastin time (aPTT) < 1.5 x ULN, unless the patient is receiving anticoagulation therapy provided INR or PTT is within the therapeutic range of the intended anticoagulant therapy.
    • Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN) ---This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
    • AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal
    • Measured creatinine CL >30 mL/min or Calculated creatinine CL>30 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
    • Males:
    • Creatinine CL (mL/min) = Weight (kg) x (140
    • Age) 72 x serum creatinine (mg/dL)
    • Females:
    • Creatinine CL (mL/min) = Weight (kg) x (140
    • Age) x 0.85 72 x serum creatinine (mg/dL)
    • Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
    • Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the postmenopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
    • Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiationinduced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
    • Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
    • Availability of baseline archival tumor tissue obtained for correlative studies dated within 8 weeks of study registration.
    • Either FFPE tumor tissue block or a minimum of fifteen 5μm unstained FFPE slides and fifteen 10μm unstained FFPE slides with an associated pathology report is required.
    • Patients without adequate baseline tumor tissue or have archival tumor tissue >8 weeks from registration must undergo cystoscopic tumor biopsy, meeting the above tissue criteria.

    Exclusion Criteria:

    • Patients with primary TCC of the ureter, urethra, or renal pelvis without TCC of the bladder
    • Inoperable tumor(s) with fixation to the pelvic wall on clinical exam
    • Any previous systemic chemotherapy or radiotherapy for TCC of bladder
    • Participation in another clinical study with an investigational product during the last 6 months
    • Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
    • Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
    • History of another primary malignancy except for:
    • Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drug and of low potential risk for recurrence
    • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
    • Adequately treated carcinoma in situ without evidence of disease (e.g. cervical cancer in situ)
    • Receipt of the last dose of intravesical chemotherapy or biologic therapy ≤ 42 days (6 weeks) prior to the first dose of study drug for patients who have received prior intravesical chemotherapy or biologic therapy (e.g. BCG)
    • Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart) for durvalumab + oleclumab cohorts only. Patient safety and the cardiac EKG should be consulted as needed.
    • Any unresolved toxicity NCI CTCAE version 5.0 Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
    • Patients with Grade ≥2 neuropathy will be evaluated on a case-bycase basis after consultation with the Study Physician.
    • Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab and/or oleclumab may be included only after consultation with the Study Physician.
    • Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g. hormone replacement therapy) is acceptable.
    • Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
    • History of allogenic organ transplantation
    • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g. colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
    • Patients with vitiligo or alopecia
    • Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement
    • Any chronic skin condition that does not require systemic therapy
    • Patients without active disease in the last 5 years may be included but only after consultation with the study physician
    • Patients with celiac disease controlled by diet alone
    • Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
    • History of leptomeningeal carcinomatosis
    • Brain metastases or spinal cord compression. Patients with suspected brain metastases at screening should have an MRI (preferred) or CT each preferably with IV contrast of the brain prior to study entry.
    • History of active primary immunodeficiency
    • Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
    • Current or prior use of immunosuppressive medication within 14 days before the first dose of study drug. The following are exceptions to this criterion:
    • Intranasal, inhaled, topical steroids, or local steroid injections (e.g. intra articular injection)
    • Systemic corticosteroids at physiologic doses not to exceed 10 mg/ day of prednisone or its equivalent
    • Steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication)
    • Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
    • Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 180 days after the last dose of durvalumab + oleclumab or 90 days after the last dose of durvalumab monotherapy, whichever is the longer time period
    • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
    • Prior randomization or treatment in a previous durvalumab and/or oleclumab clinical study regardless of treatment arm assignment
    • Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements

    View trial on ClinicalTrials.gov


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    Published March 4, 2020
  • A Multicenter Study Evaluating Safety and Efficacy of TAR-200 in Subjects With Muscle-Invasive Urothelial Carcinoma of the Bladder Who Are Ineligible for or Refuse Cisplatin-based Chemotherapy and Who Are Unfit for Radical Cystectomy

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    A Multicenter Study Evaluating Safety and Efficacy of TAR-200 in Subjects With Muscle-Invasive Urothelial Carcinoma of the Bladder Who Are Ineligible for or Refuse Cisplatin-based Chemotherapy and Who Are Unfit for Radical Cystectomy


    Condition: Bladder Cancer TNM Staging Primary Tumor (T) T2A, Bladder Cancer TNM Staging Primary Tumor (T) T2B, Bladder Cancer TNM Staging Primary Tumor (T) T3A, Bladder Cancer TNM Staging Primary Tumor (T) T3B

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03404791

    Sponsor: Taris Biomedical LLC

    Phase: Phase 1

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    1. Histological proof of non-metastatic muscle-invasive urothelial cell carcinoma of the bladder.
    2. Subject must have been as fully resected as possible per the physician's judgment.
    3. Subjects must be deemed unfit for RC due to comorbid conditions with a risk of mortality.
    4. Subjects must refuse or be deemed ineligible for cisplatin-based chemotherapy.
    5. Subject must refuse or not be eligible for radiotherapy.
    6. Life expectancy of at least 4 months.
    7. Adequate bone marrow, liver, and renal function.
    8. Subjects must be willing to undergo a cystoscopy.
    9. Subjects must be willing to undergo a biopsy for assessment of clinical response.
    10. Written informed consent and authorization for release of personal health information obtained according to local laws.
    11. Age ≥18 years at the time of informed consent.
    12. Females of childbearing potential must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 4 weeks after treatment discontinuation. Subject's partner must also use barrier protection while subject is on study until 4 weeks after treatment discontinuation.
    13. Males must be willing to use an effective method of contraception/method to avoid seminal transfer (barrier method or abstinence) from the time consent is signed until 4 weeks after treatment discontinuation. Subject's partner must also use barrier protection while subject is on study until 4 weeks after treatment discontinuation.
    14. Females of childbearing potential must have a negative pregnancy test within 21 days prior to Study Day 0.

    Exclusion Criteria:

    1. Other active malignancies.
    2. Presence of any bladder or urethral anatomic feature that in the opinion of the Investigator may prevent the safe placement, indwelling use, or removal of TAR-2
    3. Pyeloureteral tube externalized to the skin (ureteral stent or unilateral nephrostomy tube is allowed).
    4. Evidence of bladder perforation during diagnostic cystoscopy.
    5. Bladder post-void residual volume (PVR) of >750 mL.
    6. Concurrent clinically significant infections as determined by the treating Investigator.
    7. Known hypersensitivity to gemcitabine (or other drug excipients) or chemically related drugs.
    8. Known hypersensitivity to the device constituent or TARIS Inserter materials.
    9. Use of an investigational product within 30 days or 5 half-lives, whichever is longer, preceding Study Day
    10. Female subject who is lactating/breastfeeding.
    11. Difficulty providing blood samples.
    12. Unwilling or unable to provide informed consent or comply with the requirements of this protocol, including the presence of any condition (physical, mental or social) that is likely to affect the subject's return for scheduled visits and follow-up.
    13. Other unspecified reasons that, in the opinion of the Investigator, make the subject unsuitable for enrollment.

    View trial on ClinicalTrials.gov


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    Published July 12, 2019
  • A Multicenter Study of TAR-200 in Combination With Nivolumab (OPDIVO) in Subjects With Muscle-Invasive Urothelial Carcinoma of the Bladder Who Are Scheduled for Radical Cystectomy and Are Ineligible for or Refusing Platinum-Based Neoadjuvant Chemotherapy

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    A Multicenter Study of TAR-200 in Combination With Nivolumab (OPDIVO) in Subjects With Muscle-Invasive Urothelial Carcinoma of the Bladder Who Are Scheduled for Radical Cystectomy and Are Ineligible for or Refusing Platinum-Based Neoadjuvant Chemotherapy


    Condition: Bladder Cancer TNM Staging Primary Tumor (T) T2, Bladder Cancer TNM Staging Primary Tumor (T) T2A, Bladder Cancer TNM Staging Primary Tumor (T) T2B, Bladder Cancer TNM Staging Primary Tumor (T) T3, Bladder Cancer TNM Staging Primary Tumor (T) T3A, Bladder Cancer TNM Staging Primary Tumor (T) T3B, Bladder Cancer TNM Staging Regional Lymph Node (N) N0, Bladder Cancer TNM Staging Regional Lymph Node (N) N1, Bladder Cancer TNM Staging Distant Metastasis (M) M0

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03518320

    Sponsor: Taris Biomedical LLC

    Phase: Phase 1

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • 1. Histological proof of muscle-invasive urothelial carcinoma of the bladder (stage cT2-cT3b, N0-1, M0). Subjects with mixed histology are required to have documented dominant transitional cell pattern with no more than 10% squamous differentiation and 10% glandular differentiation. Micropapillary/sarcomatoid/adenocarcinoma/plasmacytoid variants are not allowed. 2. Subjects with a total tumor size of ≤2 cm following TURBT are eligible. Subjects with a tumor or tumors totaling >2 cm at screening must undergo a second debulking TURBT to reduce the tumor(s) to ≤2 cm to be eligible for treatment. 3. Adequate bone marrow, liver, and renal function, as documented by the following laboratory assessments conducted within 28 days prior to dosing:
    • Hemoglobin ≥9.0 g/dL
    • Absolute neutrophil count (ANC) ≥1,500/mm3
    • Platelet count ≥100,000/mm3
    • Total bilirubin ≤1.5x upper limit of normal (ULN)
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5x ULN
    • Glomerular filtration rate (GFR) ≥30 ml/min/1.73 m2 (assessed using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) 4. Willing to undergo multiple cystoscopies during the study for TAR-200 removal and post-insertion examination. 5. Deemed eligible for and willing to undergo RC by the attending urologist. 6. Subjects must refuse cisplatin-based combination chemotherapy (and understand the risk and benefits of doing so) or be deemed ineligible for cisplatin-based chemotherapy by meeting at least one of the following criteria:
    • GFR <60 mL/min/1.73 m2 (assessed using the CKD-EPI equation)
    • Common Terminology Criteria for Adverse Events (CTCAE) v4 Grade ≥2 audiometric hearing loss
    • CTCAE v4 Grade ≥2 peripheral neuropathy 7. Prior systemic chemotherapy for indications other than urothelial cell carcinoma of the bladder is permitted. All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to Grade 1 (National Cancer Institute CTCAE version 4.03) or baseline before administration of study drug. Participants with toxicities attributed to prior anti cancer therapy which are not expected to resolve and result in long lasting sequelae, such as peripheral neuropathy after platinum-based therapy or audiometric hearing loss, are permitted to enroll. 8. Written informed consent and authorization for release of personal health information obtained according to local laws. 9. Age ≥18 years at the time of consent. 10. Women of childbearing potential (WOCBP) must be willing to use a highly effective method of contraception (hormonal or intrauterine device [IUD] method of birth control with a failure rate of <1% when used consistently and correctly; or abstinence) for the duration of treatment with TAR-200 in combination with nivolumab plus 5 half-lives of study treatment, plus 30 days (duration of ovulatory cycle), for a total of 5 months post treatment completion. Note: WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements, but still must undergo pregnancy testing as described in this protocol. 11. WOCBP must have a negative pregnancy test within 24 hours prior to Study Day 0. 12. Males must be willing to use an effective method of contraception to avoid seminal transfer (double barrier method) or abstinence for the duration of treatment with TAR 200 in combination with nivolumab plus 5 half-lives of the study treatment, plus 90 days (duration of sperm turnover), for a total of 7 months post-treatment completion. In addition, male participants must be willing to refrain from sperm donation during this time. 13. Azoospermic males should also use double barrier contraceptive methods to avoid contamination of the non-treatment sexual partner. Exclusion Criteria: 1. Active malignancies within 3 years except for those with a negligible risk of metastasis or death treated with expected curative outcome. 2. Prior systemic chemotherapy for urothelial cell carcinoma of the bladder. 3. Prior treatment with an anti-programmed death-1 (PD-1), anti-PD-L1, anti PD L2, anti-CD137, or anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co stimulation or checkpoint pathways. 4. Pelvic radiotherapy administered within less than 6 months prior to enrollment. Subjects who received radiotherapy ≥6 months prior to enrollment must demonstrate no cystoscopic evidence or symptoms of radiation cystitis. 5. Subjects who require immunosuppressive medications such as methotrexate, tumor necrosis factor inhibitors, or systemic corticosteroids (>10 mg/day prednisone equivalents) within 2 weeks prior to study drug administration. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. 6. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. 7. Presence of any bladder or urethral anatomic feature that in the opinion of the investigator may prevent the safe placement, indwelling use, or removal of TAR 200. 8. Pyeloureteral tube externalized to the skin is exclusionary. Unilateral nephrostomy tube or ureteral stent is permitted as long as it does not interfere with placement or retention of TAR-200 in the bladder. 9. Indwelling catheters are not permitted. 10. Subjects with evidence of bladder perforation during diagnostic cystoscopy may be treated if perforation has resolved prior to dosing. 11. Bladder post-void residual volume of >500 mL. 12. History of diagnosis of neurogenic bladder requiring intermittent catheterization. 13. Active, uncontrolled urogenital bacterial, viral or fungal infections, including urinary tract infection (UTI). Skin/nail fungal infections are not exclusionary. Subjects with active shingles (varicella zoster infection) will be excluded from the study. 14. Subjects with a positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus RNA or hepatitis C antibody (HCV antibody) indicating acute or chronic infection. 15. Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome. Note: Testing for HIV must be performed at sites where mandated locally. 16. Uncontrolled adrenal insufficiency. 17. New York Heart Association Functional Classification of Heart Failure: Class III or IV (Appendix 1). 18. Eastern Cooperative Oncology Group (ECOG) performance status ≥2. 19. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements. 20. Subjects who have had a history of acute diverticulitis, intra-abdominal abscess, gastrointestinal obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation. 21. Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity. 22. Subjects must have recovered from the effects of major surgery requiring general anesthetic or significant traumatic injury at least 14 days before Study Day 0. 23. History of allergy or hypersensitivity to gemcitabine (or other drug excipients in TAR-200) or drugs chemically-related to gemcitabine. 24. History of allergy or hypersensitivity to the device constituent or Inserter materials. 25. History of allergy or hypersensitivity to nivolumab drug components. 26. Female subject who is pregnant (as verified by urine test at time of screening) or lactating or of childbearing potential and not using acceptable methods of contraception. 27. Difficulty providing blood samples. 28. Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent. 29. Use of an investigational product (IP) within 30 days or 5 half-lives, whichever is longer, preceding Study Day 0. 30. Prisoners or subjects who are involuntarily incarcerated. (Note: under certain specific circumstances a person who has been imprisoned may be included or permitted to continue as a subject. Strict conditions apply and sponsor approval is required.) 31. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness Other protocol defined inclusion/

    Exclusion Criteria:

    1. Active malignancies within 3 years except for those with a negligible risk of metastasis or death treated with expected curative outcome.
    2. Prior systemic chemotherapy for urothelial cell carcinoma of the bladder.
    3. Prior treatment with an anti-programmed death-1 (PD-1), anti-PD-L1, anti PD L2, anti-CD137, or anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co stimulation or checkpoint pathways.
    4. Pelvic radiotherapy administered within less than 6 months prior to enrollment. Subjects who received radiotherapy ≥6 months prior to enrollment must demonstrate no cystoscopic evidence or symptoms of radiation cystitis.
    5. Subjects who require immunosuppressive medications such as methotrexate, tumor necrosis factor inhibitors, or systemic corticosteroids (>10 mg/day prednisone equivalents) within 2 weeks prior to study drug administration. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
    6. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
    7. Presence of any bladder or urethral anatomic feature that in the opinion of the investigator may prevent the safe placement, indwelling use, or removal of TAR 2
    8. Pyeloureteral tube externalized to the skin is exclusionary. Unilateral nephrostomy tube or ureteral stent is permitted as long as it does not interfere with placement or retention of TAR-200 in the bladder.
    9. Indwelling catheters are not permitted.
    10. Subjects with evidence of bladder perforation during diagnostic cystoscopy may be treated if perforation has resolved prior to dosing.
    11. Bladder post-void residual volume of >500 mL.
    12. History of diagnosis of neurogenic bladder requiring intermittent catheterization.
    13. Active, uncontrolled urogenital bacterial, viral or fungal infections, including urinary tract infection (UTI). Skin/nail fungal infections are not exclusionary. Subjects with active shingles (varicella zoster infection) will be excluded from the study.
    14. Subjects with a positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus RNA or hepatitis C antibody (HCV antibody) indicating acute or chronic infection.
    15. Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome. Note: Testing for HIV must be performed at sites where mandated locally.
    16. Uncontrolled adrenal insufficiency.
    17. New York Heart Association Functional Classification of Heart Failure: Class III or IV (Appendix 1).
    18. Eastern Cooperative Oncology Group (ECOG) performance status ≥
    19. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
    20. Subjects who have had a history of acute diverticulitis, intra-abdominal abscess, gastrointestinal obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation.
    21. Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
    22. Subjects must have recovered from the effects of major surgery requiring general anesthetic or significant traumatic injury at least 14 days before Study Day
    23. History of allergy or hypersensitivity to gemcitabine (or other drug excipients in TAR-200) or drugs chemically-related to gemcitabine.
    24. History of allergy or hypersensitivity to the device constituent or Inserter materials.
    25. History of allergy or hypersensitivity to nivolumab drug components.
    26. Female subject who is pregnant (as verified by urine test at time of screening) or lactating or of childbearing potential and not using acceptable methods of contraception.
    27. Difficulty providing blood samples.
    28. Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
    29. Use of an investigational product (IP) within 30 days or 5 half-lives, whichever is longer, preceding Study Day
    30. Prisoners or subjects who are involuntarily incarcerated. (Note: under certain specific circumstances a person who has been imprisoned may be included or permitted to continue as a subject. Strict conditions apply and sponsor approval is required.)
    31. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness Other protocol defined inclusion/exclusion criteria could apply.

    View trial on ClinicalTrials.gov


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    Published October 13, 2018
  • A Phase 1b-2 Study of Mitomycin-c/ Capecitabine ChemoRadiotherapy Combined With Nivolumab Monotherapy or Ipilumimab and Nivolumab, as Bladder Sparing Curative Treatment for Muscle Invasive Bladder Cancer: the CRIMI Study

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    A Phase 1b-2 Study of Mitomycin-c/ Capecitabine ChemoRadiotherapy Combined With Nivolumab Monotherapy or Ipilumimab and Nivolumab, as Bladder Sparing Curative Treatment for Muscle Invasive Bladder Cancer: the CRIMI Study


    Condition: Urinary Bladder Cancer, Invasive Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03844256

    Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

    Phase: Phase 1/Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Be willing and able to provide written informed consent for the trial.
    • Be ≥ 18 years of age on day of signing informed consent.
    • Wish to preserve their bladder function or be ineligible for cystectomy.
    • Must have undergone transurethral biopsy of the bladder tumor, within 35 days of planned treatment commencement. The patient should have a histologically-confirmed diagnosis of muscle-invasive T2-T4a, N0-1M0 urothelial cell carcinoma of the bladder.
    • Must have undergone maximal transurethral resection of the bladder tumour, to an extent that is judged as safe by the urologist performing the resection, within 35 days of planned treatment commencement.
    • Subjects with tumors of mixed urothelial/non-urothelial cell histology are allowed, but urothelial cell carcinoma must be the predominant histology (>50%). Subjects with predominant or exclusively non-urothelial cell histology are not allowed.
    • Have planned for chemoradiotherapy as definitive treatment.
    • Have a performance status of 0 or 1 on the ECOG Performance Scale
    • Have a bladder function that is accessible for cystoscopical follow up.
    • Demonstrate adequate organ function. All screening labs should be performed within 28 days of registering the patient on the trial.
    • Female participants of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to registering the patient. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
    • Female participants of childbearing potential should be willing to one highly effective method of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 5 month after the last dose of study medication Participants of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
    • Male participants should agree to use condoms starting with the first dose of study therapy through 7 month after the last dose of study therapy.
    • Willing to consent to the use of their collected tumor specimen, blood and urine as detailed in the protocol for future scientific research including but not limited to DNA, RNA and protein based biomarker detection.

    Exclusion Criteria:

    • Has DPD deficiency.
    • Has concurrent extra-vesical (i.e. urethra, ureter or renal pelvis) urothelial cell carcinoma of the urothelium. Patients who have involvement of the prostatic urethra with urothelial cell cancer may be included if the location can be safely incorporated in the radiation field.
    • Extensive or multifocal bladder carcinoma in situ (CIS) precluding curative chemoradiotherapy.
    • Evidence of distant metastatic disease on a CT or FDG PET/CT chest/abdomen/pelvis performed within 28 days prior to study entry. Up to 3 metastatic lymphnodes in the pelvis (below the common iliac arteries) are allowed, if these can be incorporated in the radiotherapy field.
    • Prior pelvic lymph-adenectomy
    • Prior pelvic radiotherapy
    • Has had prior intravenous chemotherapy, targeted small molecule therapy, or radiation therapy for treatment of bladder cancer. Prior intravesical use of BCG and MMC is permissible.
    • Unsuitable for concurrent MMC / capecitabine based ChRT based on pre-existing medical conditions.
    • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to the first dose of treatment.
    • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy over 10mg daily prednisone (or equivalent) or any other form of immunosuppressive therapy within 14 days prior to registering the patient. Patients with adrenal insufficiency receiving replacement dose steroids are allowed on the trial.
    • Has a known history of active TB (Bacillus Tuberculosis)
    • Hypersensitivity to nivolumab and/or ipilimumab or any of its excipients.
    • Prior or concurrent known additional malignancy of any site unless disease free for 5 years. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer, Stage T1a well differentiated prostatic carcinoma in men (Gleason = 3+3, PSA <5)
    • Has any history of active autoimmune disease, Stevens-Johnson syndrome or Guillain-Barre. Exceptions to this are: 1. Patients with autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone 2. Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen
    • Has known history of, or any evidence of active, non-infectious pneumonitis.
    • Has an active infection requiring systemic therapy.
    • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
    • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
    • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
    • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
    • Has an Human Immunodeficiency Virus (HIV) infection with a PCR detectable viral load.
    • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
    • Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.

    View trial on ClinicalTrials.gov


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    Published January 15, 2020
  • A Phase 1b, Multicenter, Open Label Study Evaluating Safety, Tolerability and Preliminary Efficacy of GemRIS 225 mg in Subjects With Muscle-Invasive Transitional Cell Carcinoma of the Bladder

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    A Phase 1b, Multicenter, Open Label Study Evaluating Safety, Tolerability and Preliminary Efficacy of GemRIS 225 mg in Subjects With Muscle-Invasive Transitional Cell Carcinoma of the Bladder


    Condition: Urinary Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02722538

    Sponsor: Taris Biomedical LLC

    Phase: Phase 1

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Histological proof of muscle-invasive transitional cell carcinoma of the bladder (stage II-III). Subjects with evidence of metastatic nodal disease to the obuturator or presacral lymph nodes only may be included (N1 M0). Subjects with any degree of fixation of the pelvic sidewall are not eligible.
    • In Arm 1, subjects must have residual visible tumor following TURBT. In Arm 2, subjects must be fully resected (i.e., no visible tumor or as little tumor as possible) after restaging TURBT 2-6 weeks prior to Study Day 0.
    • Adequate bone marrow, liver, and renal function, as assessed by the following requirements conducted within 21 days prior to dosing: 1. Hemoglobin ≥ 9.0 g/dL 2. Absolute neutrophil count (ANC) ≥ 1,500/mm3 3. Platelet count ≥ 100,000/mm3 4. Total bilirubin ≤ 1.5xULN (upper limit of normal) 5. Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 2.5xULN 6. Glomerular Filtration Rate (GFR) ≥ 30% (≥ 30 ml/min/1.73 m2)
    • Subjects must be willing to undergo a cystoscopy on study for investigational product removal.
    • Eligible for and willing to undergo RC per the attending urologist.
    • Subjects must be deemed ineligible for cisplatin-based combination chemotherapy by the attending medical oncologist.
    • Subjects medically eligible for neoadjuvant cisplatin-based combination chemotherapy who refuse this therapeutic option and understand the risks and benefits of doing so.
    • Prior radiation therapy is allowed provided that no radiation therapy was administered to the urinary bladder.
    • Written informed consent and Health Insurance Portability and Accountability Act of 1966 (HIPAA) authorization for release of personal health information.
    • Age > 18 years at the time of consent.

    Exclusion Criteria:

    • Active malignancies within 12 months with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome.
    • Prior systemic chemotherapy for transitional cell carcinoma of the bladder. Any other prior systemic chemotherapy for a non-urothelial carcinoma must have been completed > 5 years prior to initiation of study.
    • Previous exposure to gemcitabine instillations.
    • Currently receiving other intravesical chemotherapy.
    • Concurrent clinically significant infections as determined by the treating investigator.
    • Presence of any bladder or urethral anatomic feature that in the opinion of the investigator may prevent the safe placement, indwelling use or removal of TAR-200.
    • Documented history of vesicoureteral reflux or the presence of an indwelling ureteral stent or nephrostomy tube at the time of screening.
    • Pelvic radiotherapy administered within less than 6 months prior to enrollment. Subjects who received radiotherapy ≥ 6 months prior to enrollment must demonstrate no cystoscopic evidence or symptoms of radiation cystitis.
    • Bladder Post-Void Residual Volume (PVR) of > 250-mL.
    • Active, uncontrolled urogenital bacterial, viral or fungal infections, including urinary tract infection that in the opinion of the investigator, contraindicates participation. Skin/nail fungal infections are not exclusionary. Subjects with active shingles (varicella zoster infection) will be excluded from the study.
    • History or presence of any significant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, gynecological, endocrine, immunological, dermatological, neurological or psychiatric disease or disorder that, in the opinion of the investigator, contraindicates participation.
    • History of diagnosis of neurogenic bladder.
    • Concomitant immunosuppressive medications, such as methotrexate or TNF inhibitors, within 2 weeks of Study Day 0, exclusive of steroid doses ≤ 5 mg daily.
    • Difficulty providing blood samples.
    • Unwilling or unable to provide informed consent or comply with the requirements of this protocol, including the presence of any condition (physical, mental or social) that is likely to affect the subject's return for scheduled visits and follow-up.
    • Other unspecified reasons that, in the opinion of the investigator or TARIS, make the subject unsuitable for enrollment.

    View trial on ClinicalTrials.gov


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    Published June 29, 2017
  • A Phase 2 Study of Check Point Inhibitor, Durvalumab (Medi4736) for Bacillus Calmette-Guérin (BCG) Refractory Urothelial Carcinoma in Situ (CIS) of the Bladder

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    A Phase 2 Study of Check Point Inhibitor, Durvalumab (Medi4736) for Bacillus Calmette-Guérin (BCG) Refractory Urothelial Carcinoma in Situ (CIS) of the Bladder


    Condition: Carcinoma in Situ of Bladder, Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02901548

    Sponsor: H. Lee Moffitt Cancer Center and Research Institute

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Must have pathologically confirmed urothelial carcinoma in situ (CIS) of the bladder that meet one of the following criteria: 1. Persistence of high-grade CIS at 6 months following an adequate course of BCG; OR
    • 2. Stage/grade progression at 3 months after induction BCG; OR
    • 3. Recurrence of high-grade CIS after achieving a disease-free state (i.e., CR) following induction of an adequate course of BCG that occurs < 9 months after the last exposure to BCG; OR
    • 4. Persistent CIS noted on the bladder biopsies within 3 months of completing at least 2 induction BCG (minimum of five weekly instillations). An adequate course of BCG should be defined as at least one course of induction (minimum of five weekly instillations) and one maintenance (two of three instillations) in a 6 months period, with an exception for any patient with grade/stage progression after induction BCG (minimum of five weekly instillations).
    • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
    • Adequate organ and marrow function.
    • Written informed consent and any locally required authorization (e.g., HIPAA in the USA, EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.
    • Females must not be pregnant, or breast feeding and must have a negative urine or serum pregnancy test within 28 days prior to treatment on day 1. Females of childbearing potential who are sexually active with a nonsterilized male partner must use a highly effective method of contraception from the time of screening, and must agree to continue using such precautions for 90 days after the final dose of Durvalumab. They must also refrain from egg cell donation for 90 days after the final dose of Durvalumab.
    • Nonsterilized males who are sexually active with a female partner of childbearing potential must use a highly effective method of contraception and refrain from sperm donation from Day 1 through 90 days after receipt of the final dose of Durvalumab.

    Exclusion Criteria:

    • Muscle invasive (T2 or above) urothelial carcinoma or urothelial carcinoma outside the bladder.
    • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) or previous enrolment in the present study.
    • Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab.
    • History of another primary malignancy except for: Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drug and of low potential risk for recurrence; Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; Adequately treated carcinoma in situ without evidence of disease e.g., cervical cancer in situ.
    • Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, tyrosine kinase inhibitor, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) ≤ 30 days prior to the first dose of study drug and within 6 weeks for nitrosourea, mitomycin C or intravesical therapy).
    • Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Frediricia's Correction.
    • Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
    • Any unresolved toxicity (CTCAE grade 2 or above) from previous anti-cancer therapy. [Potential participants with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy)].
    • Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1.
    • Active or prior documented autoimmune disease within the past 2 years. NOTE: Potential participants with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
    • Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
    • History of primary immunodeficiency.
    • History of allogeneic organ transplant.
    • History of pneumonitis.
    • History of hypersensitivity to durvalumab or any excipient.
    • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any participant known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the participant to give written informed consent.
    • Known history of previous clinical diagnosis of tuberculosis.
    • History of leptomeningeal carcinomatosis.
    • Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab.
    • Females who are pregnant, breast-feeding or males or females of reproductive potential who are not employing an effective method of birth control.
    • Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results.
    • Uncontrolled seizures.
    • Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids.

    View trial on ClinicalTrials.gov


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    Published October 9, 2017
  • A Phase 3, Randomized, Double-blind, Placebo-controlled Clinical Trial to Study the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Chemoradiotherapy (CRT) Versus CRT Alone in Participants With Muscle-invasive Bladder Cancer (MIBC) (KEY

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    A Phase 3, Randomized, Double-blind, Placebo-controlled Clinical Trial to Study the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Chemoradiotherapy (CRT) Versus CRT Alone in Participants With Muscle-invasive Bladder Cancer (MIBC) (KEYNOTE-992)


    Condition: Urinary Bladder Neoplasms

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT04241185

    Sponsor: Merck Sharp & Dohme LLC

    Phase: Phase 3

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Has a histologically confirmed initial diagnosis of muscle-invasive bladder cancer (MIBC) with predominant urothelial histology
    • Has clinically nonmetastatic bladder cancer (N0M0)
    • Has planned and is eligible to receive chemoradiotherapy (CRT) and one of the protocol-specified radiosensitizing chemotherapy regimens
    • Has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
    • Demonstrates adequate organ function
    • Male participants are eligible to participate if they agree to the following during the intervention period and for at least 90 days after the last dose of CRT treatment:
    • Refrain from donating sperm
    • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent; or must agree to use contraception unless confirmed to be azoospermic
    • A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
    • Is not a woman of childbearing potential (WOCBP)
    • Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 180 days the time needed to eliminate each study intervention after the last dose of study intervention; and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. The length of time required to continue contraception for each study intervention is as follows: MK-3475
    • 120 days and CRT
    • 180 days

    Exclusion Criteria:

    • Has the presence of diffuse carcinoma in situ (CIS) (multiple foci of CIS) throughout the bladder
    • Has the presence of urothelial carcinoma (UC) at any site outside of the urinary bladder in the previous 2 years except for Ta stage/T1 stage/CIS of the upper tract if the participant has undergone a complete nephroureterectomy
    • Has a known additional malignancy that is progressing or has required active therapy within the past 3 years, except basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer or other carcinoma in situ that has undergone potentially curative therapy
    • Has the presence of bilateral hydronephrosis
    • Has limited bladder function with frequency of small amounts of urine (< 30 mL), urinary incontinence, or requires self-catheterization or a permanent indwelling catheter
    • Has received prior pelvic/local radiation therapy or any antineoplastic treatment for muscle-invasive bladder cancer (MIBC). Treatment for non-muscle invasive bladder cancer (NMIBC) with intravesical instillation therapy that was completed ≥28 days prior to randomization is allowed. Prior systemic treatment of NMIBC is not permitted.
    • Received prior therapy with an anti-PD-1 (programmed cell death protein 1), anti-PD-L1 (programmed death-ligand 1), or anti-PD-L2 (programmed cell death 1 ligand 2), or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., CTLA-4 [cytotoxic T-lymphocyte-associated protein 4], OX 40, or CD137 [cluster of differentiation 137])
    • Has received a live vaccine within 30 days before the first dose of study medication
    • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study medication
    • Has known severe hypersensitivity (≥Grade 3) to the selected chemotherapy regimen, and/or any of their excipients and excipients of pembrolizumab
    • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of study medication
    • Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
    • Has a history of non-infectious pneumonitis that required steroids or has current pneumonitis
    • Has an active infection requiring systemic therapy
    • Has a known history of human immunodeficiency virus (HIV) infection
    • Has a known history of hepatitis B or known active hepatitis C virus infection
    • Has a known history of active tuberculosis (TB; Bacillus tuberculosis)
    • Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
    • Has had an allogenic tissue/solid organ transplant

    View trial on ClinicalTrials.gov


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    Published May 20, 2020
  • A Phase 3, Randomized, Study of Neoadjuvant Chemotherapy Alone Versus Neoadjuvant Chemotherapy Plus Nivolumab or Nivolumab and BMS-986205, Followed by Continued Post- Surgery Therapy With Nivolumab or Nivolumab and BMS-986205 in Participants With Muscle-

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    A Phase 3, Randomized, Study of Neoadjuvant Chemotherapy Alone Versus Neoadjuvant Chemotherapy Plus Nivolumab or Nivolumab and BMS-986205, Followed by Continued Post- Surgery Therapy With Nivolumab or Nivolumab and BMS-986205 in Participants With Muscle- Invasive Bladder Cancer


    Condition: Urinary Bladder Neoplasms, Muscle-Invasive Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03661320

    Sponsor: Bristol-Myers Squibb

    Phase: Phase 3

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Participant must be deemed eligible for Radial Cystectomy (RC) by his/her oncologist and/or urologist, and must agree to undergo Radial Cystectomy (RC) after completion of neoadjuvant therapy.
    • Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1

    Exclusion Criteria:

    • Clinical evidence of positive lymph node(s) (LN) (≥ 10 mm in short axis) or metastatic bladder cancer
    • Prior systemic therapy, radiation therapy, or surgery for bladder cancer other than trans urethral resection of bladder tumor (TURBT) or biopsies is also not permitted

    View trial on ClinicalTrials.gov


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    Published June 4, 2019
  • A Phase I/II Open-Label Multicenter Study to Evaluate the Safety and Efficacy of Oral APL-1202 in Combination With Tislelizumab Compared to Tislelizumab Alone as Neoadjuvant Therapy in Patients With Muscle Invasive Bladder Cancer (MIBC)

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    A Phase I/II Open-Label Multicenter Study to Evaluate the Safety and Efficacy of Oral APL-1202 in Combination With Tislelizumab Compared to Tislelizumab Alone as Neoadjuvant Therapy in Patients With Muscle Invasive Bladder Cancer (MIBC)


    Condition: Muscle Invasive Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT04813107

    Sponsor: Jiangsu Yahong Meditech Co., Ltd aka Asieris

    Phase: Phase 1/Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • 1. Willing and able to provide written informed consent. 2. Age ≥ 18 years. 3. Histopathologically confirmed transitional cell carcinoma of the bladder. Patients with mixed histologies are required to have a dominant (i.e. > 50%) transitional cell pattern. 4. Radical cystectomy is planned (according to local guidelines). 5. Patients who refuse neoadjuvant cisplatin based chemotherapy or in whom neoadjuvant cisplatin based therapy is contraindicated. Contraindications to cisplatin is defined by meeting at least one of the following criteria:
    • Impaired renal function with calculated CrCl 30 to 59 mL/min (by Cockcroft-Gault equation).
    • Eastern Cooperative Oncology Group (ECOG) Performance Status 2.
    • CTCAE v.5 Grade ≥2 audiometric hearing loss.
    • In the clinical judgement of the investigator, potential adverse effects from cisplatin-based neoadjuvant chemotherapy outweighs its benefits. 6. Clinical stage T2-T4a N0 M0 disease by CT (or MRI) (within 4 weeks of randomization). 7. Residual disease after transurethral resection of bladder (TURB) (surgical opinion, cystoscopy or radiological presence). 8. Availability of representative formalin-fixed paraffin-embedded (FFPE) tumor specimens or unstained slides, with an associated pathology report, and determined to be evaluable for tumor PD-L1 expression prior to study enrollment; 9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2. 10. Adequate hematologic and end-organ functions:
    • Hemoglobin > 9.0 g/dL;
    • Absolute neutrophil count (ANC) > 1.5×109 /L;
    • Platelet count > 100×109 /L;
    • Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).
    • Aspartate aminotransferase (AST) /alanine aminotransferase (ALT) ≤ 2.5 x institutional upper limit of normal ULN.
    • CrCl (calculated using Cockcroft-Gault equation) ≥ 30 mL/min (calculated CrCl ≥ 50 mL/min in Phase Ⅰ: Dose-Escalation).
    • INR < 1.5. This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose. 11. Female patients should be surgically sterilized or post-menopausal or must agree to take effective contraceptive measures during the treatment. Male patients must be surgically sterilized or must agree to take effective contraceptive measures during treatment. Patients must continue to take contraceptive measures for 3 months after the investigational therapy was completed.

    Exclusion Criteria:

    1. Previous systemic therapy for bladder cancer.
    2. Malignancies other than urothelial bladder cancer within 5 years prior to cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ of breast treated surgically with curative intent).
    3. Evidence of measurable nodal or metastatic disease.
    4. Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome).
    5. Pregnant female patients. All female patients with a positive pregnancy test within 2 weeks prior to the first dose of study treatment will be excluded from the study.
    6. Significant cardiovascular disease, such as New York Heart Association cardiac disease (more than Class II), myocardial infarction within 3 months prior to enrollment, unstable arrhythmias, or unstable angina.
    7. Severe infections within 4 weeks prior to enrollment in the study including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
    8. Major surgical procedure within 4 weeks prior to enrollment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis.
    9. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
    10. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the tislelizumab or APL-1202 formulation.
    11. History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
    12. History of autoimmune-related hypothyroidism, unless on a stable dose of thyroid-replacement hormone.
    13. History of idiopathic pulmonary fibrosis.
    14. Uncontrolled Type 1 diabetes mellitus.
    15. Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or calcium > 12 mg/dL or corrected serum calcium > ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab.
    16. Prior allogeneic stem cell or solid organ transplantation.
    17. Positive test for HIV.
    18. Uncontrolled hepatitis infection.
    19. Active tuberculosis.
    20. Optic nerve disorders or with a history of optic nerve disorders.
    21. Cataract or with a history of cataract.
    22. Prior treatment with anti-programmed death-1 (PD-1), or anti-PD-L1 therapeutic antibody or pathway-targeting agents.
    23. Patients taking regular oral steroids, above the allowed limit of 10 mg/day methylprednisolone/prednisone or analogues, for any reason. Patients must not have had steroids for 4 weeks prior to study entry.
    24. Administration of vaccine within 4 weeks prior to enrollment or anticipation that such a vaccine will be required during the study.
    25. Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 4 weeks prior to enrollment.
    26. Treatment with systemic immunostimulatory agents within 4 weeks prior to enrollment.

    View trial on ClinicalTrials.gov


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    Published November 30, 2023
  • A Phase II Open Label Single Arm Study of Adjuvant Nivolumab Following Chemo-Radiation in Localized Muscle-Invasive Bladder Cancer (NEXT)

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    A Phase II Open Label Single Arm Study of Adjuvant Nivolumab Following Chemo-Radiation in Localized Muscle-Invasive Bladder Cancer (NEXT)


    Condition: Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03171025

    Sponsor: University of Utah

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Patients with muscularis propria invasion clinical stages 2 to 4 (T2-4b, N0 or N+, M0 or T1 with N+), who are not candidates for radical cystectomy.
    • Patients may have undergone partial cystectomy for removal of bladder tumor prior to chemoradiation. Patients who have M1 disease at any time prior to start of treatment are not eligible.
    • Staging is determined prior to chemoradiation
    • Patients have been evaluated by a urologic oncologist to determine eligibility for radical cystectomy prior to chemoradiation. Patients may not be candidates for radical cystectomy due to one or more reasons such as but not limited to comorbidities, age, surgical risk or patient refusal to undergo radical cystectomy. Patients who refuse to undergo radical cystectomy are not required to be evaluated by a urologic oncologist.
    • Patients must have histologically proven primary adenocarcinoma, transitional, squamous-cell, or sarcomatoid carcinoma primary of the bladder, urethra, or lower ureter.
    • Treating investigator has determined that the patients are not a candidate for radical cystectomy. Patients have been evaluated by a urologic oncologist to determine eligibility for radical cystectomy prior to chemoradiation. Patients may not be candidates for radical cystectomy due to one or more reasons such as, but not limited to, comorbidities, age, surgical risk, or patient refusal to undergo radical cystectomy.
    • Tumor tissue from the most recently resected site of disease (preferable) or from the transurethral resection that yielded the initial muscle invasive diagnosis must be provided for biomarker correlative analyses. Enrollment is permitted if adequate archived tissue is unavailable.
    • Patients must have received systemic radiosensitizing chemotherapy with definitive pelvic radiation therapy. Patients may have received partial amount of chemotherapy and radiation (both) to be eligible.
    • Platinum based chemotherapy prior to chemoradiation is permitted but not mandatory
    • Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤2
    • Age ≥18.
    • Adequate bone marrow function White Blood Cell (WBC) > 2000/µl, neutrophils >1500/µl, Hemoglobin >9.0 g/dl.
    • Serum bilirubin and aminotransferase values less than 1.5 times the upper limit of the normal range
    • Creatinine clearance of 20 ml/min or greater as measured by the Cockroft-Gault formula
    • Able to start study treatment within 90 days of completion of chemoradiation.
    • Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
    • Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 5 months after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
    • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 7 months after the last dose of study therapy.
    • All toxicities attributed to prior anti-cancer therapy other than nephropathy, neuropathy, hearing loss, alopecia and fatigue must have resolved to Grade 1 (NCI CTCAE version 4.03) or baseline before administration of study drug. Subjects with toxicities attributed to prior anti-cancer therapy which are not expected to resolve and result in long lasting sequelae, such as neuropathy after platinum based therapy, are permitted to enroll.
    • Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.

    Exclusion Criteria:

    • Evidence of distant metastases or lymph node metastasis (es) that was not within the radiation field.
    • Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin. A history of localized early stage malignancy that has undergone potentially curative therapy or is low grade and does not require active treatment is allowed.
    • Diffuse bladder carcinoma in situ (CIS) that was not able to be encompassed in a boost radiotherapy volume
    • Patients with inflammatory bowel disease
    • Patients with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
    • Patients with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 day of study drug administration. Inhaled, ocular, intraarticular, intranasal and topical steroids are permitted.
    • Patients with a known chronic immunocompromised state, HIV infection or active Hepatitis B or Hepatitis C infection.
    • Pregnancy or women of childbearing potential not willing to use contraception and men who are sexually active and not willing/able to use medically acceptable forms of contraception and breast-feeding women not willing to stop breastfeeding during study.
    • Severe active co-morbidity as determined by the investigator or principal investigator
    • Life expectancy less than 2 years

    View trial on ClinicalTrials.gov


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    Published October 9, 2017
  • A Phase II Study Investigating Preoperative MPDL3280A in Operable Transitional Cell Carcinoma of the Bladder (ABACUS)

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    A Phase II Study Investigating Preoperative MPDL3280A in Operable Transitional Cell Carcinoma of the Bladder (ABACUS)


    Condition: Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02662309

    Sponsor: Queen Mary University of London

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    1. Willing and able to provide written informed consent
    2. Ability to comply with the protocol
    3. Age ≥ 18 years
    4. Histopathologically confirmed transitional cell carcinoma (T2-T4a) of the bladder. Patients with mixed histologies are required to have a dominant transitional cell pattern.
    5. Residual disease after TURBT (surgical opinion, cystoscopy or radiological presence).
    6. Fit and planned for cystectomy (according to local guidelines).
    7. N0 or M0 disease CT or MRI (within 4 weeks of registration)
    8. Representative formalin-fixed paraffin embedded (FFPE) bladder tumour samples with an associated pathology report that are determined to be available and sufficient for central testing.
    9. Patients who refuse neoadjuvant cisplatin based chemotherapy or in whom neoadjuvant cisplatin based therapy is not appropriate.
    10. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
    11. Negative pregnancy test within 2 weeks of Day 1 Cycle 1 for female patients of childbearing potential.
    12. For female patients of childbearing potential to use a highly effecting form(s) of contraception (i.e. one that results in a low failure rate [<1% per year] when used consistently and correctly) and to continue its use for 90 days after the last dose of MPDL3280A.
    13. Adequate hematologic and end-organ function within 4 weeks prior to the first study treatment

    Exclusion Criteria:

    1. Pregnant and lactating female patients.
    2. Major surgical procedure within 4 weeks prior to enrolment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis.
    3. Previously intravenous chemotherapy for bladder cancer.
    4. Patients with prior allogeneic stem cell or solid organ transplantation.
    5. Prior treatment with CD137 agonists, anti-CTLA-4, anti−programmed death−1 (PD-1), or anti−PD-L1 therapeutic antibody or pathway-targeting agents.
    6. Patients must not have had oral or IV steroids for 14 days prior to study entry. The use of inhaled corticosteroids, physiologic replacement doses of glucocorticoids (i.e., for adrenal insufficiency), and mineralocorticoids (e.g., fludrocortisone) is allowed.
    7. Received therapeutic oral or intravenous (IV) antibiotics within 14 days prior to enrolment (Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible).
    8. Administration of a live, attenuated vaccine within 4 weeks prior to enrolment or anticipation that such a live, attenuated vaccine will be required during the study.
    9. Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin [IL]−2) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to enrolment.
    10. Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 4 weeks prior to enrolment.
    11. Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome).
    12. Malignancies other than UBC within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent) or localized prostate cancer treated with curative intent and absence of prostate-specific antigen (PSA) relapse or incidental prostate cancer (Gleason score ≤ 3 + 4 and PSA < 10 ng/mL undergoing active surveillance and treatment naive).
    13. Severe infections within 4 weeks prior to enrolment in the study including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia.
    14. Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to enrolment, unstable arrhythmias, or unstable angina.
    15. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan (History of radiation pneumonitis in the radiation field (fibrosis) is permitted).
    16. Patients with uncontrolled Type 1 diabetes mellitus. Patients with Type 1 diabetes controlled on a stable insulin regimen are eligible.
    17. Patients with active hepatitis infection (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
    18. Positive test for HIV
    19. Patients with active tuberculosis
    20. History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug.
    21. Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or Ca > 12 mg/dL or corrected serum calcium > the institutional ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab. Patients who are receiving bisphosphonate therapy or denosumab specifically to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible. Patients who are receiving denosumab prior to enrollment must be willing and eligible to receive a bisphosphonate instead while on study.
    22. History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
    23. Patients with a history of autoimmune-related hypothyroidism, unless on a stable dose of thyroid-replacement hormone.
    24. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
    25. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the MPDL3280A formulation

    View trial on ClinicalTrials.gov


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    Published June 29, 2017
  • A Phase II Study of Chemoradiation for Bladder Preservation in Patients With Muscle Invasive Bladder Carcinoma After Complete Response to Neoadjuvant Chemotherapy

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    A Phase II Study of Chemoradiation for Bladder Preservation in Patients With Muscle Invasive Bladder Carcinoma After Complete Response to Neoadjuvant Chemotherapy


    Condition: Bladder Cancer, Bladder Carcinoma, Transition Cell Cancer, Muscle Invasive Bladder Carcinoma

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02145390

    Sponsor: University of Miami

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • 1. Pathologically proven diagnosis of primary carcinoma of the bladder(transitional cell cancer). Must be operable patients with muscularis propria invasion and American Joint Committee on Cancer (AJCC) clinical stages T2-4a, N0 or N+, M0. Patients with prostatic urethra involvement with transitional cell cancer (TCC) are eligible if it is completely resected and the patient has no evidence of stromal invasion of the prostate. 2. Patients must be able to tolerate systemic chemotherapy combined with pelvic radiation therapy and radical cystectomy. 3. Zubrod Performance Status of ≤1. 4. Age ≥18. 5. Complete Blood Count (CBC)/differential obtained no more than 8 weeks prior to enrollment on study, with adequate bone marrow function defined as follows:
    • White Blood Cell (WBC) ≥ 4000/ml
    • Absolute neutrophil count (ANC) ≥1,800 cells/mm
    • Platelets ≥100,000 cells/mm
    • Hemoglobin ≥ 10.0 mg/dl (Note: the use of transfusion or other intervention to achieve this level is acceptable) 6. Serum bilirubin of 2.0mg or less; 7. Serum creatinine of 1.5mg or less; creatinine clearance of 60ml/min or greater no more than 8 weeks prior to enrollment (Note: calculated creatinine clearance is permissible, using Cockcroft-Gault formula. If the creatinine clearance is greater than 60ml/min, then a serum creatinine of up to 1.8mg is allowable at the discretion of the principal investigator.) Note: Prechemotherapy laboratory investigations and Eastern Cooperative Oncology Group (ECOG) evaluation must meet inclusion criteria irrespective of where they were drawn, retroactive, prior to cycle 1 of cisplatin/gemcitabine. Inclusion criteria from these initial investigations will be used for evaluation of enrollment eligibility. 8. Patients must be willing and able to provide study-specific informed consent prior to study entry

    Exclusion Criteria:

    • 1. Tumor related untreated active hydronephrosis 2. Evidence of distant metastases. 3. Diffuse bladder carcinoma in situ (CIS) not able to be encompassed in a boost radiotherapy volume. 4. Previous systemic chemotherapy (for any cancer) or pelvic radiation therapy 5. A prior or concurrent malignancy of any other site or histology unless the patient has been disease free for greater than or equal to five years except for non-melanoma skin cancer and/or stage T1a prostate cancer or carcinoma in situ of the uterine cervix 6. Patients that are not candidates for radical cystectomy (T4b disease are considered unresectable) 7. Pregnancy or women of childbearing potential [not post-menopausal or permanently sterilized (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy)] and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic 8. Severe active co-morbidity:
    • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
    • Transmural myocardial infarction within the last 6 months
    • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
    • Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of enrollment
    • History of hepatic insufficiency resulting in clinical jaundice and/or coagulation defects (Note: laboratory tests for liver function and coagulation parameters are not required for enrollment into this protocol)
    • Known diagnosis of Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control (CDC) definition (Note: HIV testing is not required for enrollment into this protocol). The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
    • As determined by the investigator or principal investigator

    View trial on ClinicalTrials.gov


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    Published June 29, 2017
  • A Phase II Study of the Anti-PD-L1 Antibody MPDL3280A in Subjects With Non-metastatic Transitional Cell Carcinoma of the Bladder

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    Phase II Study of Neoadjuvant Atezolizumab-based Immunotherapy for Patients With Urothelial Carcinoma (NEBULA)


    Condition: Carcinoma, Transitional Cell

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02451423

    Sponsor: Lawrence Fong

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • 18 years of age or older
    • Eastern Cooperative Oncology Group (ECOG) performance status 0, 1
    • Histologically document transitional cell carcinoma with the presence of any of the following stages: Carcinoma in situ (CIS), high-grade Ta, any grade T1, or any grade cT2-T4, considered appropriate for radical cystectomy. Subjects with mixed histology are required to have a dominant transitional cell carcinoma (TCC) pattern.
    • For subjects with non-muscle-invasive bladder cancer (NMIBC), Bacillus Calmette-Guerin (BCG) -refractory or BCG-resistant disease. BCG-refractory disease is defined as the absence of a complete response by 6 months in patients who have received induction and maintenance OR two induction courses of BCG. BCG-resistant disease is defined as persistent or recurrent disease after 2 induction courses of BCG within 1 year OR cancer recurrence within 1 year of initiation of therapy for patients who have received induction plus maintenance BCG therapy. Subjects with NMIBC must be suitable for and willing to undergo a radical cystectomy at the completion of study therapy.
    • For subjects with muscle invasive disease: not suitable neoadjuvant cisplatin-based chemotherapy as determined by the following:
    • Creatinine clearance less than 60ml/min. Glomerular filtration rate (GFR) should be assessed by calculation from serum/plasma creatinine (Cockcroft-Gault formula)
    • Common Terminology Criteria for Adverse Events (CTCAE) Grade >/= 2 hearing loss
    • CTCAE Grade >/= 2 neuropathy
    • Subjects with nonmetastatic muscle-invasive bladder cancer (MIBC) not meeting the above criteria are still eligible provided the patient declines neoadjuvant cisplatin-based chemotherapy, after specific informed consent describing the known benefits of cisplatin-based chemotherapy. The reason for declining must be documented.
    • Adequate bone marrow function defined as
    • White Blood Cell count (WBC) > 2500 cells/mm3
    • Absolute Neutrophil Count (ANC) > 1500 cells/mm3
    • Hemoglobin > 9 g/dL. Patients may be transfused or receive erythropoietic treatment to meet this criterion.
    • Platelet count > 100,000 cells/mm3
    • Adequate renal function: Serum creatinine < 2 mg/dL OR calculated Creatinine Clearance (CrCl) > 30ml/min
    • Serum bilirubin < 1.5 x ULN (except for patients with documented Gilbert's disease)
    • aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x upper limit of normal (ULN)
    • Ability to understand and willingness to sign a written informed consent.
    • Have available evaluable archival tumor tissue for PD-L1 biomarker assessment. Presence of PD-L1 antigen on tumors is NOT required for study entry.
    • The effects of MPDL3280A on the developing human fetus are unknown. For this reason women of child-bearing potential and men must agree to use adequate contraception prior to study entry, during study participation, and for 90 days after study treatment discontinuation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 90 days after completion of study drug administration.

    Exclusion Criteria:

    • Subjects with primary TCC of the ureter, urethra, or renal pelvis without TCC of the bladder are not allowed.
    • Known distant metastatic disease (e.g. pulmonary or hepatic metastases).
    • Subjects with malignant lymphadenectomy in the abdomen or pelvis considered appropriate for radical cystectomy and lymphadenectomy with the goal of complete resection of all malignant disease are allowed.
    • Intravesical chemo- or biologic therapy within 6 weeks of first treatment.
    • Prior systemic chemotherapy or radiation therapy for transitional cell carcinoma of the bladder.
    • Subjects who have received prior intravesical chemotherapy are allowed.
    • Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), anti-programmed cell death protein 1 (PD-1) and anti-PD-L1 therapeutic antibodies.
    • History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegner's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vacuities, or glomerulonephritis.
    • Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible for this study.
    • Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen are eligible for this study.
    • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
    • History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
    • Chronic liver disease
    • HIV or active hepatitis B virus (HBV); chronic or acute; defined as having a positive hepatitis B surface antigen [Bag] test at screening) or active hepatitis C
    • Patients with past HBV infection or resolved HBV infection (defined as the presence of hepatitis B core antibody (HBcAb) and absence of HBsAg) are eligible. HBV DNA must be obtained in these patients prior to Cycle 1, Day 1, but detection of HBV DNA in these patients will not exclude study participation.
    • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
    • Active tuberculosis
    • Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
    • Prior allogeneic stem cell or solid organ transplant
    • Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study. Inactivated vaccines (such as hepatitis A or polio vaccines) are permitted during the study.
    • Influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live attenuated influenza vaccine (e.g., FluMist) within 4 weeks prior to Cycle 1, Day 1 and for at least 12 weeks after the last dose.
    • Clinically significant active infection or uncontrolled medical condition
    • Uncontrolled cystitis, significant bladder pain or spasms, or gross hematuria that in the opinion of the treating investigator, should preclude study entry.
    • Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina
    • Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction < 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate.
    • Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure other than cystectomy during the course of the study
    • Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor (anti-TNF) agents within 2 weeks prior to Cycle 1, Day 1, or anticipated requirement for systemic immunosuppressive medications during the trial
    • Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled in the study after discussion with and approval by the Study Chair.
    • The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone for adrenal insufficiency) is allowed.
    • Pregnant or nursing women are excluded
    • Known hypersensitivity to Chinese hamster ovary (CHO) cell products or any component of the MPDL3280A formulation
    • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
    • Malignancies other than Urological Cancers (UC) within 5 years prior to Cycle 1, Day 1, with the exception of those with a low risk of metastasis or death treated with expected curative outcome (such as, but not limited to, adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated with curative intent and absence of Prostate-specific antigen (PSA) relapse, or ductal carcinoma in situ of the breast treated surgically with curative intent) or incidental prostate cancer (T1a, Gleason score ≤ 6 and PSA < 0.5 ng/mL).

    View trial on ClinicalTrials.gov


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    Published June 29, 2017
  • A Phase III Multicentre Randomised Controlled Trial to Compare the Efficacy of Robotically Assisted Radical Cystectomy (RARC) and Intracorporeal Urinary Diversion With Open Radical Cystectomy (ORC) in Patients With Bladder Cancer

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    A Phase III Multicentre Randomised Controlled Trial to Compare the Efficacy of Robotically Assisted Radical Cystectomy (RARC) and Intracorporeal Urinary Diversion With Open Radical Cystectomy (ORC) in Patients With Bladder Cancer


    Condition: Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03049410

    Sponsor: University College, London

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Participants must be over 18 years of age.
    • Male or female
    • Histopathological confirmation of bladder cancer (UCC, SCC, adenocarcinoma or rare variant)
    • CIS or stage pTa or pT1 or ≥pT2 or mobile bladder mass on bimanual examination under anaesthesia (see Section 22: Definitions for TNM definitions)
    • Node status ≤ N1 on imaging criteria or PET -ve outside pelvis
    • ECOG grade 0, 1, 2 or 3
    • Able to give informed written consent to participate.

    Exclusion Criteria:

    • Unwilling to undergo cystectomy.
    • Previous abdominal surgery rendering them unsuitable for either iRARC or ORC.
    • Patients with upper urinary tract disease
    • Concomitant disease that would render the patient unsuitable for the trial
    • Pregnant or lactating females
    • Previous radiotherapy for bladder cancer

    View trial on ClinicalTrials.gov


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    Published October 9, 2017
  • A Phase III, Open-Label, Multicenter, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) Versus Observation as Adjuvant Therapy in Patients With PD-L1-Selected, High-Risk Muscle-Invasive Bladder Cancer After Cystectomy

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    A Phase III, Open-Label, Multicenter, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) Versus Observation as Adjuvant Therapy in Patients With High-Risk Muscle-Invasive Urothelial Carcinoma After Surgical Resection


    Condition: Carcinoma, Transitional Cell

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02450331

    Sponsor: Hoffmann-La Roche

    Phase: Phase 3

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Histologically confirmed muscle-invasive UC (also termed transitional cell carcinoma) of the bladder or upper urinary tract (i.e., renal pelvis or ureters)
    • For participants treated with prior neoadjuvant chemotherapy: tumor stage of ypT2-4a or ypN+ (ypT2-4 or ypN+ for participants with upper urinary tract UC) and M0
    • For participants who have not received prior neoadjuvant chemotherapy: tumor stage of pT3-4a or pN+ (pT3-4 or pN+ for participants with upper urinary tract UC) and M0
    • Representative formalin-fixed paraffin-embedded tumor specimens from surgical resection (i.e., radical cystectomy, nephroureterectomy, or lymph node dissection) in paraffin blocks (blocks preferred) or at least 15 unstained slides, with an associated pathology report, for central testing and determined to be evaluable for tumor programmed death-ligand 1 (PD-L1) expression prior to study enrollment
    • Absence of residual disease and absence of metastasis, as confirmed by a negative baseline computed tomography (CT) or magnetic resonance imaging scan of the pelvis, abdomen, and chest no more than 4 weeks prior to randomization
    • Full recovery from cystectomy or nephroureterectomy within 14 weeks following surgery
    • Eastern Cooperative Oncology Group performance status of less than or equal to (
    • Life expectancy greater than or equal to (>/=) 12 weeks
    • Adequate hematologic and end-organ function
    • For women who are not postmenopausal or surgically sterile: agreement to remain abstinent or use contraceptive methods that result in a failure rate of less than (<) 1 percent (%) per year during the treatment period and for at least 5 months after the last dose of atezolizumab

    Exclusion Criteria:

    • Any approved anti-cancer therapy within 3 weeks prior to initiation of study treatment
    • Adjuvant chemotherapy or radiation therapy for UC following surgical resection
    • Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days or five half-lives of the drug prior to enrollment
    • Malignancies other than UC within 5 years prior to Cycle 1, Day 1
    • Pregnancy or breastfeeding
    • Significant cardiovascular disease
    • Severe infections within 4 weeks prior to Cycle 1, Day 1
    • Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1, Day 1
    • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
    • Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
    • History of autoimmune disease
    • Prior allogeneic stem cell or solid organ transplant
    • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
    • Positive test for human immunodeficiency virus and/or active hepatitis B or hepatitis C or tuberculosis
    • Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1
    • Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies, including anti-CD40, anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibodies

    View trial on ClinicalTrials.gov


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    Published October 13, 2018
  • A Phase III, Randomized, Open-Label, Multi-Center, Global Study to Determine the Efficacy and Safety of Durvalumab in Combination With Gemcitabine+Cisplatin for Neoadjuvant Treatment Followed by Durvalumab Alone for Adjuvant Treatment in Patients With Mus

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    A Phase III, Randomized, Open-Label, Multi-Center, Global Study to Determine the Efficacy and Safety of Durvalumab in Combination With Gemcitabine+Cisplatin for Neoadjuvant Treatment Followed by Durvalumab Alone for Adjuvant Treatment in Patients With Muscle-Invasive Bladder Cancer.


    Condition: Muscle Invasive Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03732677

    Sponsor: AstraZeneca

    Phase: Phase 3

    Eligibility:

    • Age: minimum 18 Years maximum 130 Years
    • Gender: All

    Criteria: Inclusion: - Patient resectable muscle-invasive bladder cancer with clinical stage T2-T4aN0/1M0 with transitional and mixed transitional cell histology - Patients must be planning to undergo a radical cystectomy - Patients who have not received prior systemic chemotherapy or immunotherapy for treatment of MIBC - ECOG performance status of 0 or 1 - Must have a life expectancy of at least 12 weeks at randomization Exclusion: - Evidence of lymph node (N2-N3) or metastatic (M1) disease at time of screening. - Prior pelvic radiotherapy treatment within 2 years of randomization to study - Prior exposure to immune-mediated therapy (with exclusion of Bacillus-Calmette Guerin [BCG]), including but not limited to other anti-CTLA-4, anti-PD-1, anti PD-L1, or anti-PD-L2 antibodies. - Current or prior use of immunosuppressive medication within 14 days before the first dose of investigational product (IP). The following are exceptions to this criterion: Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular injection); Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent; Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication) - Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. - Uncontrolled intercurrent illness - Active infection including Tuberculosis, Hepatitis B, Hepatitis C, and Human Immunodeficiency

    View trial on ClinicalTrials.gov


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    Published November 6, 2018
  • A Pilot Study of 18Fluorine-Fluciclovine Positron Emission Tomography/Computed Tomography for Staging Muscle Invasive Bladder Cancer Preceding Radical Cystectomy

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    A Pilot Study of 18Fluorine-Fluciclovine Positron Emission Tomography/Computed Tomography for Staging Muscle Invasive Bladder Cancer Preceding Radical Cystectomy


    Condition: Bladder Cancer, Urothelial Carcinoma

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT04018053

    Sponsor: Dana-Farber Cancer Institute

    Phase: Early Phase 1

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Participants must have histologically or cytologically confirmed urothelial carcinoma of the bladder.
    • Participants must have cT2-T4N0 disease at the time of the study, as defined by conventional CT or MRI imaging. Patients must have no definite evidence of locoregional or distant metastatic disease at the time of study eligibility, as defined by conventional imaging.
    • Radical cystectomy must be planned for the patient after the planned 18F-fluciclovine-PET/CT.
    • Patients may or may not have had prior neoadjuvant therapy prior to this study.
    • Age ≥18 years. Since no dosing or adverse event data are currently available on the use of 18F-fluciclovine in participants <18 years of age, and the majority of bladder cancer occur in the adult population [42], children are excluded from this study but will be eligible for future pediatric trials.
    • ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
    • Ability and willingness to comply with the study procedures.
    • The effects of 18F-fluciclovine on the developing human fetus are unknown. For this reason and because radiopharmaceuticals may be teratogenic, women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control; abstinence) prior to study entry and for 24 hours after the PET/CT scan is completed. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
    • Ability to understand and the willingness to sign a written informed consent document

    Exclusion Criteria:

    • Participants with other known malignancies that has required treatment in the past 3 years.
    • Pregnant women are excluded from this study because 18F-fluciclovine is a radiopharmaceutical with the potential for teratogenic effects. Because of the radiation exposure to a nursing infant from 18F-fluciclovine, women who are breastfeeding are also excluded from this study.
    • History of allergic reactions attributed to compounds of similar chemical or biologic composition to 18F-fluciclovine.
    • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
    • Contraindications for PET/CT including:
    • Severe claustrophobia
    • Any past or current condition that in the opinion of the study investigators would confound the results of the study or pose additional risk to the patient by their participation in the study

    View trial on ClinicalTrials.gov


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    Published January 13, 2020
  • A Pilot Study to Evaluate the Safety of Neoadjuvant Nivolumab Alone or in Combination With Ipilimumab for Cisplatin-Ineligible Patients With Muscle Invasive Bladder Cancer (CA209-9DJ)

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    A Pilot Study to Evaluate the Safety of Neoadjuvant Nivolumab Alone or in Combination With Ipilimumab for Cisplatin-Ineligible Patients With Muscle Invasive Bladder Cancer (CA209-9DJ)


    Condition: Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03520491

    Sponsor: Memorial Sloan Kettering Cancer Center

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Histologically confirmed diagnosis of urothelial carcinoma of the bladder. Variant histology is acceptable if there is a predominant urothelial component.
    • For MUSCLE-INVASIVE UROTHELIAL CANCER OF THE BLADDER (Cohorts 1
    • 3): ° Cystoscopically and radiographically confirmed cT2-4a cN0 cM0 disease. Patients with cT4a disease invading into the prostatic stroma with no cystoscopic confirmation of muscle invasion are eligible.
    • For UROTHELIAL CARCINOMA OF THE UPPER URINARY TRACT (URETER OR RENAL PELVIS) (Cohort U): °Histologically confirmed high grade urothelial carcinoma of the upper tract and/or radiographically visible tumor stage T2-T4a N0/x M0 disease with positive selective urinary cytology. Hydronephrosis associated with tumor on imaging or biopsy will be considered invasive by definition. (Variant histology is acceptable if there is a predominant urothelial component)
    • Patients ineligible for cisplatin based on any of the following criteria:
    • Estimated or calculated creatinine clearance ≥ 30ml/min but < 60 ml/min
    • Grade 2 or above audiometric hearing loss (per CTCAE v4.0)
    • Grade 2 or above peripheral neuropathy (per CTCAE v4.0)
    • Availability of tumor specimen block or 30 unstained slides from diagnosis of muscle-invasive disease. Patients with fewer than 30 slides available may be enrolled after discussion with the Principal Investigator.
    • Karnofsky performance status ≥ 70%.
    • Medically appropriate candidate for radical cystectomy, as per MSK Attending Urologic Oncologist
    • Age ≥ 18 years.
    • Required initial laboratory values:
    • Absolute neutrophil count ≥ 1.5 x 10^9/L
    • Platelets ≥ 100 x 10^9/L
    • Bilirubin ≤1.5 times the upper limit of normal (x ULN)
    • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN
    • PTT/PT ≤1.5 x ULN or INR < 1.7 x ULN for patients who are not receiving therapeutic anticoagulation. Patients receiving therapeutic anticoagulation should be on a stable dose.

    Exclusion Criteria:

    • Prior treatment with systemic chemotherapy for urothelial cancer, including immune checkpoint inhibitors for non-muscle invasive bladder cancer. (Prior intravesical treatment such as BCG is allowed.)
    • Prior bladder-directed radiotherapy (exclusion applies only to MIBC Cohorts 1
    • 3).
    • Presence of active autoimmune disease, symptoms, or conditions, with the following exceptions: °Subjects with type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, asymptomatic laboratory evidence of autoimmune disease (e.g.: +ANA, +RF, anti-thyroglobulin antibodies), or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
    • Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first dose of study drug. Inhaled or topical steroids, and adrenal replacement steroid doses are permitted in the absence of active autoimmune disease.
    • Unstable angina.
    • New York Heart Association (NYHA) Grade II or greater congestive heart failure.
    • History of myocardial infarction within 6 months.
    • History of stroke within 6 months.
    • Evidence of bleeding diathesis or coagulopathy. Therapeutic anticoagulation is permitted, but patients must be on a stable dose.
    • Major surgical procedure within 28 days prior to the study. (Transurethral resection of bladder tumor is permitted
    • Serious, non-healing wound, ulcer, or bone fracture.
    • Other prior malignancy active within the previous 2 years except for local or organ-confined early stage cancer that has been definitively treated with curative intent or does not require treatment, does not require ongoing treatment, has no evidence of active disease, and has a negligible risk of recurrence and is therefore unlikely to interfere with the endpoints of the study.
    • Subjects who have received prior therapy with any T cell co-stimulation or checkpoint pathways such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, anti-CD137; or other medicines specifically targeting T cells are prohibited. Prior IL-2 is permitted.
    • Prior therapy with intravesical BCG within 6 weeks of treatment.
    • Positive test for hepatitis B virus (HBV) using HBV surface antigen (HBV sAg) test or positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV antibody test indicating acute or chronic infection.
    • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
    • History of allergy to study drug component or history of severe hypersensitivity reaction to any monoclonal antibody.
    • Women who are breastfeeding or pregnant as evidenced by a positive pregnancy test within 14 days of first dose.
    • Male subjects who are unwilling to use contraception during the treatment and for at least 31 weeks after the last dose of study treatment (5 half-lives of study drug plus 90 days duration of sperm turnover).
    • Women of childbearing potential (WOCBP) not using a medically acceptable means of contraception throughout the study treatment and for at least 23 weeks following the last dose of study treatment (5 half-lives of study drug plus 30 days duration of ovulatory cycle).
    • WOCBP are defined as those who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal. Post-menopausal is defined as:
    • Amenorrhea ≥ 12 consecutive months without another cause, or
    • For women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL
    • Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.
    • Inability to comply with study and/or follow-up procedures.

    View trial on ClinicalTrials.gov


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    Published September 25, 2018
  • A Randomised Phase II Trial of Adaptive Image Guided Standard or Dose Escalated Tumour Boost Radiotherapy in the Treatment of Transitional Cell Carcinoma of the Bladder

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    A Randomised Phase II Trial of Adaptive Image Guided Standard or Dose Escalated Tumour Boost Radiotherapy in the Treatment of Transitional Cell Carcinoma of the Bladder


    Condition: Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02447549

    Sponsor: Institute of Cancer Research, United Kingdom

    Phase: Phase 2

    Eligibility:

    • Age: minimum 16 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Written informed consent
    • Age ≥16 years
    • Histologically or cytologically confirmed transitional cell carcinoma (TCC) of the bladder
    • Unifocal bladder TCC staged T2-T4a N0 M0
    • Fit to receive a radical course of radiotherapy
    • WHO performance status 0-2
    • Willing and able to comply with study procedures and follow up schedule

    Exclusion Criteria:

    • Nodal or metastatic disease
    • Widespread carcinoma in situ (CIS) or CIS remote from muscle invasive tumour or multifocal invasive disease
    • Simultaneous TCC in upper tract or urethra
    • Pregnancy
    • Active malignancy within 2 years of randomisation (not including non melanomatous skin carcinoma, previous non muscle invasive bladder tumours, NCCN low risk prostate cancer (T1/T2a, Gleason 6 PSA <10), in situ carcinoma of any site)
    • Any other conditions that in the Principal Investigator's opinion would be a contra-indication to radiotherapy (e.g. previous pelvic radiotherapy / inflammatory bowel disease)

    View trial on ClinicalTrials.gov


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    Published June 29, 2017
  • A Randomized Phase II Study of Co-Expression Extrapolation (COXEN) With Neoadjuvant Chemotherapy for Localized, Muscle-Invasive Bladder Cancer

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    A Randomized Phase II Study of Co-Expression Extrapolation (COXEN) With Neoadjuvant Chemotherapy for Localized, Muscle-Invasive Bladder Cancer


    Condition: Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02177695

    Sponsor: Southwest Oncology Group

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Histologically proven bladder cancer (pure small cell carcinoma, pure adenocarcinoma, and pure squamous cell carcinoma histologies are excluded).
    • Stage cT2-T4a N0 M0 disease.
    • Documented muscle invasive disease with at least one of the following: disease measuring at least 10 mm on cross-sectional imaging OR the presence of tumor-associated hydronephrosis.
    • Staging scans with abdominal/pelvic CT or MRI scan and CT scan or x-ray of the chest within 56 days prior to registration. If alkaline phosphatase is above the treating institution's upper limit of normal (ULN), presence of suspicious bone pain, or if other clinical suspicion, a whole body bone scan is required within 56 days prior to registration.
    • Performance status = 0 or 1
    • 18 years of age or older
    • Must have tumor tissue from transurethral resection of the bladder tumor (TURBT) available for submission that is sufficient for COXEN testing and must agree to submission of 20 (10 micron) slides plus 2 (5 micron) slides from the start and end of the 20 slides for a total of 22 unstained slides.
    • Must agree to collection of tissue (if residual disease is present), urine, and whole blood.
    • Must agree to participate in the translational medicine studies outlined in the protocol

    Exclusion Criteria:

    • Prior systemic cytotoxic chemotherapy or systemic anthracycline
    • Peripheral neuropathy >/= Grade 2
    • Class III/IV heart failure or known left ventricular ejection fraction (LVEF) < 50%
    • Clinically relevant hearing impairment > Grade 2
    • Renal function, calculated creatinine clearance < 60 mL/min
    • Hepatic function, total bilirubin > 1.5 x institutional upper limit of normal (IULN) (or > 2.5 x IULN with Gilbert's disease); AST & ALT > 2 X IULN
    • Hematologic function, absolute neutrophil count (ANC) < 1,500/mcL, hemoglobin < 9 g/dL, and platelets < 100,000/mcL
    • Hypersensitivity to cisplatin, gemcitabine, doxorubicin, vinblastine, methotrexate, or filgrastim/pegfilgrastim
    • Incidence of or uncontrolled medical illness (e.g. active cardiac symptoms, active systemic infection, etc.)
    • Pregnant or nursing females
    • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years. However, patients with localized prostate cancer who are being followed by an active surveillance program are eligible.

    View trial on ClinicalTrials.gov


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    Published June 29, 2017
  • A Randomized Phase II Trial Assessing Trimodality Therapy With or Without Adjuvant Durvalumab to Treat Patients With Muscle-Invasive Bladder Cancer

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    A Randomized Phase II Trial Assessing Trimodality Therapy With or Without Adjuvant Durvalumab to Treat Patients With Muscle-Invasive Bladder Cancer


    Condition: Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03768570

    Sponsor: Canadian Cancer Trials Group

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Histologic diagnosis of urothelial carcinoma of the bladder. Patients with mixed histology (including small cell) and urothelial carcinoma are eligible. Patients with pure small cell carcinoma will be excluded.
    • Stage T2-T4a N0M0 at time of diagnosis based on trans-urethral resection of bladder tumour, imaging, and/or bimanual examination under anesthesia.
    • CT scan of the chest/abdomen/pelvis within 8 weeks from enrollment, showing no evidence of metastatic disease.
    • Patients must be ≥ 18 years of age.
    • Patients must have a life expectancy greater than 6 months.
    • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 and a body weight of > 30kg.
    • Patients must have adequate hematologic reserve: Platelet count ≥ 75 x 10^9/L, Absolute neutrophils ≥ 1.0 x 10^9/L. Anemia will be corrected to minimum hemoglobin of 90 g/L with red cell transfusions, if necessary.
    • Patients must have an estimated creatinine clearance (Cockcroft-Gault Equation) ≥ 30 ml/min.
    • Patients must have adequate liver function with a bilirubin ≤ 1.5 ULN (if confirmed Gilbert's, eligible providing bilirubin ≤ 3 x UNL) and AST/ALT (SGOT/SGPT) < 2.5 x the upper normal limit.
    • All patients must have a tumour block from their primary tumour available and consent to release the block/cores/cut slides for correlative analyses ( and the centre/pathologist must have agreed to the submission of the specimen(s).
    • Patients have completed prior trimodality therapy (TMT) consisting of surgery, chemotherapy and radiation therapy treatment prior to enrollment. Patient should start treatment within 42 days after completion of TMT.
    • Patients must have undergone a transurethral resection prior to study enrollment.
    • Patient may have completed up to 4 cycles of cisplatin-based neo-adjuvant chemotherapy. Adjuvant chemotherapy is not permitted. Patients will have received cisplatin, given intravenously during the radiation therapy. OR Patients may have received fluorouracil and mitomycin given intravenously once weekly or gemcitabine as an alternative to cisplatin during radiotherapy.
    • The following are radiotherapy guidelines for patients treated on study. Patients will be treated to radical treatment doses using IMRT, VMAT or 4 field conformal techniques. Planning will be based on CT planning. IGRT is recommended during the radiotherapy treatment. Recognizing differences in usual radiotherapy doses used in the various participating countries and centres the following would be acceptable doses in this study. The bladder CTV will include the whole empty bladder and any extravesical extension. PTV expansion will be a minimum of 0.75 cm right, left and inferiorly, 1.5 cm Anteriorly and superiorly and 1 cm posteriorly. These minimum expansions are with Cone beam verification. For patients undergoing RT without image-guided verification 1.5 cm expansion in all directions is recommended. Acceptable doses for this study include:
    • Bladder only: 64-66 Gy in 32-33 fractions over 6.5 weeks; 50-55 Gy in 20 fractions over 4 weeks
    • Pelvis and bladder: 45-46 Gy to pelvic nodes + 17-20 Gy bladder boost in 33-35 fractions over 6.5-7 wks [Note: minimal nodal dose (if used) is 44 Gy in 32f or 40 Gy in 20f]
    • Patients receiving concurrent bladder boost: pelvis dose 40 Gy and bladder dose 50 Gy given in 20 fractions over 4 weeks. Adaptive radiotherapy techniques would be acceptable.
    • Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires in either English, French or Spanish.
    • Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate.
    • Patients must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating centre. This implies there must be reasonable geographical limits placed on patients being considered for this trial.
    • In accordance with CCTG policy, protocol treatment is to begin within 2 working days of patient enrollment.
    • Women/men of childbearing potential must have agreed to use a highly effective contraceptive method during and for 3 months following treatment.
    • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

    Exclusion Criteria:

    • Pre-existing medical conditions precluding treatment.
    • Pregnancy or lactating mothers.
    • Received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-PD-L1, including durvalumab anti-programmed cell death-ligand 2 (anti-PD-L2), anti-CD137 (4-1BB ligand, a member of the Tumour Necrosis Factor Receptor [TNFR] family), or anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
    • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease (e.g. colitis or Crohn's disease: not due to radiation reaction), diverticulitis with the exception of diverticulosis, celiac disease (controlled by diet alone) or other serious gastrointestinal chronic conditions associated with diarrhea), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis), rheumatoid arthritis, hypophysitis, uveitis, etc., within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:
    • Patients with alopecia;
    • Patients with Grave's disease, vitiligo or psoriasis not requiring systemic treatment (within the last 2 years);
    • Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement;
    • Any chronic skin condition that does not require systemic therapy.
    • Patients with active or uncontrolled intercurrent illness including, but not limited to:
    • cardiac dysfunction (symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia);
    • active peptic ulcer disease or gastritis;
    • active bleeding diatheses;
    • psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent;
    • known history of previous clinical diagnosis of tuberculosis;
    • known active human immunodeficiency virus infection (positive HIV 1/2 antibodies). HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible;
    • known active hepatitis B infection (positive HBV surface antigen (HBsAg). Patients with a past or resolved HBV infection (defined as presence of hepatitis B core antibody (anti-HBc) and absence of HBsAg) are eligible;
    • known active hepatitis C infection. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
    • History of primary immunodeficiency, history of allogenic organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 28 days of randomization or a prior history of severe (grade 3 or 4) immune mediated toxicity from other immune therapy or grade ≥ 3 infusion reaction.
    • Current or prior use of immunosuppressive medication within 28 days of study entry, with the exceptions of intranasal and inhaled corticosteroids or systemic chronic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Corticosteroids used on study for anti-emetic purpose are allowed. Corticosteroids as premedication for hypersensitivity reactions (e.g. computed tomography [CT] scan premedication) are allowed.
    • Peripheral neuropathy ≥ grade 2 (CTCAE v5.0).
    • History of allergic or hypersensitivity reactions to any study drug or their excipients.
    • Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 msec in screening ECG measured using standard institutional method or history of familial long QT syndrome.
    • History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline CT scan.
    • Any active disease condition which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy.
    • Any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol.
    • Live attenuated vaccination administered within 30 days prior to randomization.
    • Any prior carboplatin based therapy.

    View trial on ClinicalTrials.gov


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    Published March 5, 2020
  • A Randomized Phase II Trial Evaluating an Organ-conserving Strategy With Radiotherapy + CDDP + Gemcitabine vs Radiotherapy + CDDP in Muscle-infiltrative Bladder Cancer

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    A Randomized Phase II Trial Evaluating an Organ-conserving Strategy With Radiotherapy + CDDP + Gemcitabine vs Radiotherapy + CDDP in Muscle-infiltrative Bladder Cancer


    Condition: Infiltrating Bladder Urothelial Carcinoma

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT01495676

    Sponsor: Institut du Cancer de Montpellier - Val d'Aurelle

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Muscle invasive urothelial cancer (front line or following the progression of a superficial tumor), pT2-pT3 stage without lymphatic impairment (N0) and without detectable metastases (M0). An optimal macroscopic resection (TURB) have to be performed
    • The proof of invasive tumor to the muscle should be brought by a transurethral resection under anaesthesia less than 8 weeks before or, in the absence, by superficial biopsies and formal imaging. Multiples biopsies in the bladder must also be performed.
    • Age ≥ 18 years
    • Life expectancy ≥ 6 months
    • Kanorfsky index ≥ 70 % (WHO 0, 1, 2)
    • Biological criteria: neutrophils ≥ 1500/mm3, Platelets ≥ 100 000/mm3, haemoglobin ≥ 10 g/dl, creatinine clearance > 60 ml/mn
    • No distant metastases (Thorax, abdomen, and pelvic CT-scan, bone scan)
    • Efficient contraception for premenopausal women, maintained during the whole treatment and up to two months after the completion of radiotherapy.
    • No radiotherapy or chemotherapy history except for in situ bladder lesions.
    • No carcinological history except for non melanoma skin tumours, in situ uterine cervix cancer
    • No contraindication to gemcitabine or cisplatin.
    • No contraindication to radiotherapy
    • Information letter and informed consent signed
    • Patient covered by social security

    Exclusion Criteria:

    • Bladder tumors without any muscle infiltration
    • Epidermoid carcinoma or adenocarcinoma
    • Distance metastases or extrapelvic node positivity
    • Severe digestive history (ulcerative colitis, complicated diverticulitis)
    • Pregnancy and breast feeding

    View trial on ClinicalTrials.gov


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    Published January 25, 2017
  • Adjuvant Chemotherapy With Gemcitabine and Cisplatin Compared to Observation After Curative Intent Resection of Cholangiocarcinoma and Muscle Invasive Gall Bladder Carcinoma (ACTICCA-1 Trial)

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    Adjuvant Chemotherapy With Gemcitabine and Cisplatin Compared to Standard of Care After Curative Intent Resection of Cholangiocarcinoma and Muscle Invasive Gall Bladder Carcinoma (ACTICCA-1 Trial)


    Condition: Cholangiocarcinoma, Gall Bladder Carcinoma

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02170090

    Sponsor: Universitätsklinikum Hamburg-Eppendorf

    Phase: Phase 3

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Criteria: All enrolled patients will postoperatively be assessed for eligibility for the treatment phase. Additionally patients not previously enrolled into the trial for whatever reason (e.g. incidental finding during surgery) will be evaluated for eligibility. - Histologically confirmed adenocarcinoma of biliary tract (intrahepatic, hilar or extrahepatic cholangiocarcinoma or muscle invasive gallbladder carcinoma) after radical surgical therapy with macroscopically complete resection (mixed tumor entities (HCC/CCA) are excluded) - Macroscopically complete resection (R0/1) within 6 (-16) weeks before scheduled start of chemotherapy - ECOG 0-1 - Age ≥18 years - Adequate hematologic function - Adequate liver function - Adequate renal function - No active uncontrolled infection, except chronic viral hepatitis under antiviral therapy - No concurrent treatment with other experimental drugs or other anti-cancer therapy, treatment in a clinical trial within 30 days prior to randomization - Negative serum pregnancy test within 7 days of starting study treatment in pre-menopausal women and women <1 year after the onset of menopause (Note: a negative test has to be reconfirmed by a urine test, should the 7-day window be exceeded) Criteria for initial study enrolment - Written informed consent - No prior chemotherapy for cholangiocarcinoma - No previous malignancy within 3 years or concomitant malignancy, except: non-melanomatous skin cancer or adequately treated in situ cervical cancer - No severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV, unstable angina pectoris, history of myocardial infarction in the last 3 months, significant arrhythmia) - Absence of psychiatric disorder precluding understanding of information of trial related topics and giving informed consent - No serious underlying medical conditions (judged by the investigator), that could impair the ability of the patient to participate in the trial - Fertile women (< 1 year after last menstruation) and procreative men willing and able to use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) - No pregnancy or lactation

    View trial on ClinicalTrials.gov


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    Published June 29, 2017
  • Application-based Perioperative Management of the Radical Cystectomy Patient

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    Application-based Perioperative Management of the Radical Cystectomy Patient


    Condition: Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02942121

    Sponsor: University of Kansas Medical Center

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Diagnosis of recurrent Non-muscle invasive bladder cancer (NMIBC) or Muscle-invasive Bladder Cancer (MIBC) and are candidates for radical cystectomy
    • Subjects must have an internet connection and be able and willing to use an applicable device. If patients do not have an applicable device, they must be willing to borrow an iPad from the study team (to be returned at the conclusion of the study).

    Exclusion Criteria:

    • No internet access

    View trial on ClinicalTrials.gov


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    Published June 29, 2017
  • Clinical and patient reported outcomes of SPARE - a randomised feasibility study of selective bladder preservation versus radical cystectomy.

    To test the feasibility of a randomised trial in muscle invasive bladder cancer (MIBC) and compare outcomes in patients who receive neoadjuvant chemotherapy followed by radical cystectomy or selective bladder preservation, where definitive treatment (cystectomy or radiotherapy) is determined by response to chemotherapy.

    Published May 1, 2017
  • Comparative Perioperative Outcomes in Septuagenarians and Octogenarians Undergoing Radical Cystectomy for Bladder Cancer-Do Outcomes Differ?

    Treatment choice for muscle invasive bladder cancer continues to be radical cystectomy. However, radical cystectomy carries a relatively high risk of morbidity and mortality compared with other urological procedures.

    Published September 11, 2017
  • Current Concepts in the Management of Muscle Invasive Bladder Cancer.

    Bladder cancer is the ninth most common cancer in the world. Twenty to twenty-five percent of all newly diagnosed bladder cancers are muscle invasive in nature, and further, 20-25% of patients who are diagnosed with high-risk non-muscle invasive disease will eventually progress to muscle invasive disease in due course of time irrespective of adjuvant intravesical therapies.

    Published February 2, 2017
  • Ethacrynic Acid Elimination in Non-Muscle Invasive Bladder Cancer Patients Undergoing Transurethral Resection

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    Ethacrynic Acid Elimination in Non-Muscle Invasive Bladder Cancer Patients Undergoing Transurethral Resection


    Condition: Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02852564

    Sponsor: Eugene Lee, MD

    Phase: Phase 1

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • NOTE: Both patients who will and will not receive standard of care concomitant mitomycin C are eligible to enroll in this study.
    • Ability to understand and the willingness to sign a written informed consent
    • Diagnosis of presumed non-muscle invasive bladder cancer based on office based cystoscopy (primary or recurrent), and planned transurethral resection of bladder tumor (TURBT)
    • Participants must have tumors with anticipated transurethral resection time ≤ 1 hour
    • Previous history of intravesical therapy allowed
    • Age ≥ 18 years
    • Performance Status 0-1
    • Adequate organ and marrow function as defined below:
    • leukocytes ≥ 3,000/mcL
    • absolute neutrophil count ≥ 1,500/mcL
    • platelets ≥ 100,000/mcl
    • total bilirubin within normal institutional limits
    • Aspartate Aminotransferase (AST) ≤ 2.5 X institutional upper limit of normal
    • Alanine Aminotransferase (ALT) ≤ 2.5 X institutional upper limit of normal
    • creatinine ≤ 2.5 X institutional upper limit of normal
    • Women of child-bearing potential (WOCP) and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately *A woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
    • Has not undergone a hysterectomy or bilateral oophorectomy; or
    • Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months) EXCLUSION CRITERIA: Participants meeting any of the

    Exclusion Criteria:

    • Participants meeting any of the exclusion criteria at baseline will be excluded from study participation.
    • Current or anticipated use of other investigational agents.
    • Patient has known nodal or distant metastatic disease. Patients with nodal or metastatic disease require systemic chemotherapy. Furthermore, they should be excluded from this clinical trial because of their poor overall prognosis.
    • Patients with locally advanced bladder cancer based on cross-sectional imaging (suspicion of extravesical disease or hydronephrosis)
    • Patients with tumors with anticipated transurethral resection time greater than 1 hour
    • History of allergic reactions attributed to compounds of similar chemical or biologic composition to Ethacrynic acid or other agents used in study.
    • Systolic blood pressure < 90 mmHg and/or diastolic blood pressure < 50 mmHg
    • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
    • Pregnant or nursing. There is a potential for congenital abnormalities and for this regimen to harm nursing infants.

    View trial on ClinicalTrials.gov


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    Published June 29, 2017
  • Identification and Treatments of Basal Like Bladder Cancer (Study on Human Tumor Samples and Animal Models)

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    Identification and Treatments of Basal Like Bladder Cancer (Study on Human Tumor Samples and Animal Models)


    Condition: Muscle Invasive Bladder Cancer, Molecular Taxonomy

    Study Type: Observational

    Clinical Trials Identifier NCT 8-digits: NCT02648100

    Sponsor: Assistance Publique - Hôpitaux de Paris

    Phase:

    Eligibility:

    • Age: minimum 18 Years maximum 70 Years
    • Gender: All

    Inclusion Criteria:

    1. Muscle invasive bladder cancer Treatment by cystectomy Adjuvant chemotherapy for 3rd cohort Clinical trial GETUG 19 for 4th cohort

    Exclusion Criteria:

    1. FFPE material not available Follow-up data not available

    View trial on ClinicalTrials.gov


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    Published June 29, 2017
  • Impact of Positron Emission Tomography (PET) Imaging in Muscle-invasive Urothelial Carcinoma of the Bladder Staging

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    Impact of Positron Emission Tomography (PET) Imaging in Muscle-invasive Urothelial Carcinoma of the Bladder Staging


    Condition: Muscle-invasive Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02462239

    Sponsor: Ontario Clinical Oncology Group (OCOG)

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Men and women with newly diagnosed muscle-invasive high grade urothelial carcinoma of the bladder (TNM stage T2a-T4a, N0-3, M0), who are eligible for either radical cystectomy or radiotherapy-based bladder conservation.
    • Being considered for treatment of curative intent.

    Exclusion Criteria:

    • Age < 18 years.
    • ECOG performance status >2.
    • Predominant histology (>50% of specimen) involves non-urothelial cell carcinoma.
    • Prior partial cystectomy.
    • Prior pelvis surgery that obviates a completed extended lymphadenectomy (e.g., aorto-femoral/iliac bypass) or for whom the surgeon feels that their ability to perform a standard or extended pelvic node dissection would be compromised.
    • Contraindications to FDG PET-CT.
    • Inability to lie supine for imaging with PET-CT.
    • Inadequate hepatic function: (i) Bilirubin >1.5 X ULN and (ii) SGOT and Alkaline phosphatase >3 X ULN
    • History of another invasive malignancy within the previous 5 years with the exception of non-melanoma skin cancer.
    • Known pregnancy or lactating female.
    • Inability to complete the study or required follow-up.

    View trial on ClinicalTrials.gov


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    Published June 29, 2017
  • Improving Clinical Staging for Muscle Invasive Bladder Cancer Through Molecular Profiling and Improved Imaging

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    Improving Clinical Staging for Muscle Invasive Bladder Cancer Through Molecular Profiling and Improved Imaging


    Condition: Bladder Cancer

    Study Type: Observational

    Clinical Trials Identifier NCT 8-digits: NCT02203136

    Sponsor: M.D. Anderson Cancer Center

    Phase:

    Eligibility:

    • Age: minimum N/A maximum N/A
    • Gender: All

    Inclusion Criteria:

    1. Patients with biopsy proven bladder cancer of any age will be eligible for enrollment.

    Exclusion Criteria:

    1. Contraindication to pelvic MRI (metallic implants/hardware, claustrophobia)
    2. Participants who have previously received chemotherapy as part of multimodal therapy.

    View trial on ClinicalTrials.gov


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    Published June 29, 2017
  • LCCC 1209: Pilot Study of [18F] Fluorodeoxyglucose Positron Emission Tomography-Magnetic Resonance Imaging (FDG-PET-MRI) for Staging of Muscle-Invasive Bladder Cancer

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    LCCC 1209: Pilot Study of [18F] Fluorodeoxyglucose Positron Emission Tomography-Magnetic Resonance Imaging (FDG-PET-MRI) for Staging of Muscle-Invasive Bladder Cancer


    Condition: Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT01655745

    Sponsor: UNC Lineberger Comprehensive Cancer Center

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • ≥ 18 years of age (no upper age limit)
    • Informed consent obtained and signed
    • cT2/T3-N0-M0 urothelial carcinoma of the bladder
    • Planned radical cystectomy with pelvic lymph node dissection
    • No known local regional or distant metastatic disease
    • Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to FDG-PET-MRI

    Exclusion Criteria:

    • History of severe reaction to contrast-enhanced CT scan
    • Poorly controlled diabetes mellitus
    • Inability to tolerate PET and/or MRI
    • Presence of pacemaker or intracranial aneurysm clip
    • Serum creatinine >1.8 mg/dL OR GFR < 30mL/min
    • Pregnant or lactating female
    • Inability to lie flat for >1 hour
    • Body Mass Index (BMI) >35
    • History of a prior malignancy within past 5 years are excluded unless they have been disease free for 3 or more years or unless they have a completely resected non-melanoma skin cancer.
    • Substance abuse, medical, psychological, or social conditions that may interfere with the patient's participation in the study

    View trial on ClinicalTrials.gov


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    Published January 25, 2017
  • Lymphadenectomy in Urothelial Carcinoma in the Renal Pelvis and Ureter

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    Lymphadenectomy in Urothelial Carcinoma in the Renal Pelvis and Ureter


    Condition: Ureteral Neoplasms

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02607709

    Sponsor: Zealand University Hospital

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    1. Age above 18 years
    2. Locally advanced high grade urothelial carcinoma in the renal pelvis or upper 2/3 of the ureter (Clinical stage > T1)
    3. Patient with ECOG performance score of 2 and less.
    4. Able to give informed consent

    Exclusion Criteria:

    1. Clinical suspicion of non-muscle invasive UUTUC
    2. Metastatic urothelial carcinoma for the renal pelvis or upper 2/3 of the ureter
    3. Inability to understand written consent forms or give consent

    View trial on ClinicalTrials.gov


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    Published June 29, 2017
  • MDSC Clinical Assay for Cancer Detection and Monitoring in Bladder Carcinoma

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    MDSC Clinical Assay for Cancer Detection and Monitoring in Bladder Carcinoma


    Condition: No Evidence of Disease, Stage II Bladder Cancer, Stage III Bladder Cancer, Stage IVA Bladder Cancer, Stage IVB Bladder Cancer

    Study Type: Observational

    Clinical Trials Identifier NCT 8-digits: NCT02735512

    Sponsor: University of Southern California

    Phase:

    Eligibility:

    • Age: minimum N/A maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Subjects must meet the criteria for one of the three following groups:
    • Normal patients- aged 40 years and older with no evidence of hematuria or cancer
    • Patients with localized bladder cancer diagnosed by cystoscopy and pathology: T2N0M0 or T3N0M0 who have not received neoadjuvant chemotherapy
    • Patients with metastatic bladder cancer: newly diagnosed with no previous treatment for metastatic disease
    • Ability to understand and the willingness to sign a written informed consent

    Exclusion Criteria:

    • For normal subject arm: evidence of cancer or hematuria
    • For localized bladder cancer: evidence of metastatic disease, second cancer, prior chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
    • For metastatic bladder cancer: prior therapy for metastatic disease
    • Uncontrolled intercurrent illness including, but not limited to previous or current history of second malignancy unrelated to bladder cancer; autoimmune disease or immune deficiency, chronic treatment with immunomodulatory therapies (e.g. glucocorticoids); significant trauma, surgery, or infection in the past two weeks or psychiatric illness/social situations that would limit compliance with study requirements

    View trial on ClinicalTrials.gov


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    Published June 29, 2017
  • Muscle Invasive Bladder Cancer: External Beam Radiotherapy as an Alternative for Cystectomy

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    Muscle Invasive Bladder Cancer: External Beam Radiotherapy as an Alternative for Cystectomy


    Condition: Toxicity

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02748200

    Sponsor: University Hospital, Ghent

    Phase: Phase 1

    Eligibility:

    • Age: minimum 18 Years maximum 80 Years
    • Gender: All

    Inclusion Criteria:

    • histological proven diagnosis of muscle invasive bladder cancer
    • stage
    • World Health Organisation performance state 0-2
    • signed informed consent

    Exclusion Criteria:

    • contra-indication for Diffusion-Weighted-Magnetic resonance imaging

    View trial on ClinicalTrials.gov


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    Published June 29, 2017
  • Open-Label, Multicenter, Ph 3 Study to Evaluate the Efficacy and Tolerability of Intravesical Vicinium™ in Subjects With Non Muscle-Invasive Carcinoma in Situ and/or High-Grade Papillary Disease of the Bladder Treated With BCG

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    Open-Label, Multicenter, Ph 3 Study to Evaluate the Efficacy and Tolerability of Intravesical Vicinium™ in Subjects With Non Muscle-Invasive Carcinoma in Situ and/or High-Grade Papillary Disease of the Bladder Treated With BCG


    Condition: Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02449239

    Sponsor: Viventia Bio

    Phase: Phase 3

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • 1. Histologically-confirmed non muscle-invasive urothelial carcinoma (transitional cell carcinoma) of the bladder as follows: 1. CIS (with or without papillary disease) OR 2. Any grade T1 papillary disease OR 3. High-grade Ta papillary disease based on a biopsy within 8 weeks of the initial dose of study treatment. If multiple bladder biopsies are required to confirm eligibility, the last bladder biopsy to the initial dose of study treatment must be within 8 weeks. This diagnosis must be confirmed by the independent central pathology reviewer prior to subject enrollment. A subject with persistent T1 disease on the second (i.e., restaging) TURBT may be enrolled in this study only if the investigator documents the subject declines cystectomy. 2. Subjects must have received adequate BCG treatment defined as at least 2 courses of BCG, i.e., at least one induction and one maintenance course or at least 2 induction courses. The initial induction course must be at least 5 treatments within a 7-week period. The second course (induction or maintenance) must be at least 2 treatments within a 6-week period. The "5+2" doses of BCG must be given within approximately 1 year (i.e., the start of one course to start of the second course within 12 months ±1 month) and for the same disease episode for which the subject is enrolling. Treatment must be considered "full-dose" BCG (see Section 10). If additional doses or courses of BCG above the minimum "5+2" are given, these do not have to be within the same approximate 12 month timeframe. Subjects who were unable to receive at least 5 doses of BCG in a first course and at least 2 doses of BCG in a second course due to intolerance are not eligible. Subjects who began their initial course of BCG with "full-dose" BCG and required dose-reductions due to adverse events but are still able to tolerate at least "5+2" doses of BCG are considered to meet the requirement for "adequate BCG." Subjects who received less than "full dose" BCG (e.g., 1/3rd dosing) as a standard regimen and not due to dose reductions because of AEs are not eligible. The BCG may have been given in combination with interferon. When BCG is given simultaneously in combination with interferon, 1/3rd dosing of BCG is acceptable. 3. The subject's disease is refractory or has relapsed following adequate BCG treatment. Refractory disease is defined as disease which persists at the first evaluation following adequate BCG. Relapsed disease is defined as having a complete response to adequate BCG but recurs at a subsequent evaluation. Subjects will enroll into one of three cohorts based on their type of disease and the time to refractory/relapsed disease following their last dose of BCG as follows:
    • Cohort 1: Subjects with CIS with or without associated papillary disease whose disease is determined to be refractory or relapsed within 6 months of the last dose of adequate BCG treatment.
    • Cohort 2: Subjects with CIS with or without associated papillary disease whose disease is determined to be refractory or relapsed more than 6 months but within 11 months of the last dose of adequate BCG treatment.
    • Cohort 3: Subjects with high-grade Ta or any grade T1 papillary disease (without CIS) whose disease is determined to be refractory or relapsed within 6 months of the last dose of adequate BCG treatment. For eligibility and cohort assignment, 6 months is defined as 30 weeks i.e., 26 weeks (6 months) plus an additional 4 weeks to accommodate scheduling variations and for diagnostic work-up and 11 months is defined as 50 weeks i.e., 48 weeks (11 months) plus an additional 2 weeks to accommodate scheduling variations and for diagnostic work-up. For subjects enrolling in Cohort 2: The investigator documents he/she would not treat the subject with additional BCG at the time of study entry. 4. Male or non-pregnant, non-breastfeeding female, age 18 years or older at date of consent. 5. All women of childbearing potential (WOCBP) must have a negative pregnancy test within 7 days of the first dose of study therapy. A woman is not of childbearing potential if she has undergone surgical sterilization (bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy) or if she is ≥55 years of age and has had no menstrual bleeding of any kind including menstrual period, irregular bleeding, spotting, etc., for at least 12 months and there is no other cause of amenorrhea (e.g., hormonal therapy, prior chemotherapy). 6. All sexually active subjects agree to use barrier contraception (i.e., condoms) while receiving study treatment and for 120 days following their last dose of study treatment. WOCBP and males whose sexual partners are WOCBP agree to use barrier contraception and a second form of contraception while receiving study treatment and for 120 days following their last dose of study treatment. 7. Karnofsky performance status ≥ 60 (Appendix 1). 8. Adequate organ function, as defined by the following criteria:
    • Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x upper limit of normal (ULN);
    • Total serum bilirubin ≤ 1.5 x ULN (CTCAE Grade ≤ 1);
    • Serum creatinine ≤ 1.5 x ULN; or a creatinine clearance ≥40 mL/min;
    • Hemoglobin ≥8.0 g/dL;
    • Absolute neutrophil count ≥1500/mm3;
    • Platelets ≥75,000/mm3 9. Ability to understand and sign an Independent Ethics Committee- or Institutional Review Board-approved informed consent document indicating that the subject (or legally acceptable representative) has been informed of all aspects of the trial and is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. The informed consent document must be signed prior to the subject undergoing tests or procedures solely for determining study eligibility and prior to receiving any protocol treatment.

    Exclusion Criteria:

    • 1. The subject is pregnant or breastfeeding. 2. Evidence of urethral or upper tract transitional cell carcinoma (TCC) within the past 2 years. Subjects with T1 disease must have no evidence of upper or lower tract disease or a more advanced stage of disease by CT urogram or MRI urogram of the abdomen and pelvis performed within 8 weeks of the first dose of study treatment. If intravenous contrast is contraindicated, retrograde ureteropyelography, or CT or MRI without intravenous contrast may be performed. 3. Subjects with hydronephrosis, except for those subjects where hydronephrosis has been longstanding (i.e., predates the diagnosis of the CIS, Ta or T1 by more than 2 years) and diagnostic evaluation at Screening shows no evidence of tumor. Subjects with hydronephrosis that is unequivocally unrelated to upper tract malignancy may be considered eligible with Sponsor approval. 4. Any intravesicular or other chemotherapy treatment within 2 weeks or any investigational agent within 4 weeks prior to the initial dose of study drug. 5. History of recurrent severe urinary tract infections (UTIs) per investigator judgment. Subjects with a current UTI requiring antibiotic treatment may defer the initiation of Vicinium treatment on Day 1 until resolution of the UTI (even if this extends the screening period requirements to start of Vicinium treatment). 6. Active, uncontrolled impairment of the urogenital, renal, hepatobiliary, cardiovascular, gastrointestinal, neurologic or hematopoietic systems which, in the opinion of the Investigator, would predispose the subject to the development of complications from the administration of intravesical therapy and/or general anesthesia. 7. The subject has a diagnosis of another malignancy within 2 years before the first dose of study treatment, except for superficial skin cancer or localized solid tumors deemed cured by surgery and not treated with systemic anticancer therapy and not expected to require anticancer therapy in the next 2 years i.e., while the subject may be taking study treatment. However, subjects with low-risk prostate cancer, e.g.:
    • Clinically localized disease (≤T2a) and
    • Gleason score 6 (3+3) and
    • Serum PSA <10 ng/mL undergoing active surveillance may be enrolled with agreement of the sponsor. 8. A QTc interval of >470 msec by the Fridericia formula (QTcF), at the Screening ECG. If the subject's QTcF is >470 msec on the initial ECG, a total of 3 ECGs should be obtained at least 3 minutes apart and all within 30 minutes. The average of the 3 QTcF's will be used to determine eligibility. Known or suspected causes of prolonged QTc can be treated (e.g., hypocalcemia, hypokalemia, hypomagnesimia) and the ECGs may be repeated. If the subject initiates treatment with a drug known to prolong the QTc during the Screening period after the initial Screening ECGs were obtained, the Screening ECGs must be repeated once the new drug has reached steady state to ensure the average QTcF remains ≤470 msec. For subject's whose heart rate is <60 bpm, the Bazett correction formula (QTcB) may be used. 9. Subjects who, in the opinion of the Investigator, cannot tolerate intravesical administration or intravesical surgical manipulation (cystoscopy, biopsy) due to the presence of serious comorbid condition(s) (e.g., uncontrolled cardiac or respiratory disorders). 10. Local or severe allergy to any components of the drug regimen.

    View trial on ClinicalTrials.gov


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    Published June 29, 2017
  • Pembrolizumab With Chemoradiotherapy as Treatment for Muscle Invasive Bladder Cancer

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    Pembrolizumab With Chemoradiotherapy as Treatment for Muscle Invasive Bladder Cancer


    Condition: Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02662062

    Sponsor: Australian and New Zealand Urogenital and Prostate Cancer Trials Group

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • 1. Be willing and able to provide written informed consent for the trial. 2. Be 18 years of age on day of signing informed consent. 3. Have histologically-confirmed diagnosis of muscle-invasive T2-T4a, Nx or N0 urothelial cell carcinoma of the bladder. Subjects with tumors of mixed transitional/non-transitional cell histology are allowed, but transitional cell carcinoma must be the predominant histology (>50%). Subjects with predominant or exclusively non-transitional cell histology are not allowed. 4. Must have undergone maximal transurethral resection of the bladder tumour, as is judged as safe as possible by the urologist performing the resection, within 42 days of treatment. Where patient has only had a biopsy/partial resection and is otherwise eligible for entry into the study, the case should be rediscussed with the referring urologist to see whether further resection would be feasible prior to embarking with the chemo-radiotherapy. 5. Have elected not to undergo radical cystectomy, or are unsuitable for radical cystectomy. 6. Planned for chemoradiotherapy as definitive treatment. 7. Have a performance status of 0 or 1 on the ECOG Performance Scale 8. Demonstrate adequate organ function as defined below, all screening labs should be performed within 10 days of registering the patient on the trial.
    • Absolute neutrophil count (ANC): ≥1.5 X 10^9/L
    • Platelets: ≥100 X 10^9/L
    • Hemoglobin: ≥9 g/dL without transfusion or EPO dependency
    • Calculated creatinine clearance ≥50 mL/min
    • Serum total bilirubin: ≤ 1.5 X ULN OR
    • Direct bilirubin ≤ ULN for participants with total bilirubin levels: > 1.5 ULN
    • AST and ALT: ≤ 2.5 X ULN
    • Albumin: >25 g/dL
    • International Normalized Ration (INR) or Prothrombin Time (PT): ≤1.5 X ULN unless participant is receiving anticoagulant therapy (as long as PT or PTT is within therapeutic range of intended use of anticoagulants)
    • Activated Partial Thromboplastin Time (aPTT): ≤1.5 X ULN unless participant is receiving anticoagulant therapy (as long as PT or PTT is within therapeutic range of intended use of anticoagulants) 9. Female participant of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to registering the patient. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 10. Female participants of childbearing potential should be willing to use two methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Participants of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. 11. Male participants should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. 12. Willing to consent to the use of their collected tumour specimen, blood and urine as detailed in the protocol for future scientific research including but not limited to DNA, RNA and protein based biomarker detection.

    Exclusion Criteria:

    • 1. Has concurrent extra-vesical (i.e. urethra, ureter or renal pelvis) urothelial cell carcinoma of the urothelium. Patients who have involvement of the prostatic urethra with urothelial cell cancer (TCC) that was visibly completely resected and no evidence of stromal invasion of the prostate remain eligible. 2. Evidence of tumour-related moderate/severe hydronephrosis unless stented or with nephrostomy to preserve renal function. 3. Extensive or multifocal bladder carcinoma in situ (CIS) precluding curative chemoradiotherapy. 4. Bulky T3/T4a tumours unsuitable for curative treatment (i.e. >10 cms in any dimension); node positive disease 5. Evidence of distant metastatic disease on CT chest/abdomen/pelvis performed within 42 days prior to study entry. Patients with pelvic lymph nodes deemed to be 'positive' are not eligible for the study unless histological confirmation of the largest most suspicious node is negative for malignancy. Patients with known CNS metastatic disease are excluded from the study 6. Prior pelvic radiotherapy 7. Has had prior intravenous chemotherapy, targeted small molecule therapy, or radiation therapy for treatment of bladder cancer. Prior intravesical use of BCG and mitomycin is permissible. 8. Unsuitable for concurrent cisplatin based chemoradiotherapy based on:
    • CTCAE v.4.03, Grade >2 audiometric hearing loss (25dB in two consecutive wave ranges) if previously performed.
    • CTCAE v.4.03, Grade >2 peripheral neuropathy 9. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to the first dose of treatment. 10. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to registering the patient. Patients with adrenal insufficiency receiving replacement dose steroids are allowed on the trial. 11. Has a known history of active TB (Bacillus Tuberculosis) 12. Hypersensitivity to pembrolizumab or any of its excipients. 13. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. 14. Prior or concurrent known additional malignancy of any site unless disease free for 5 years. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer, Stage T1a well differentiated prostatic carcinoma in men (Gleason = 3+3, PSA <5) 15. Has any history of active autoimmune disease, Stevens-Johnson syndrome or Guillain-Barre. Exceptions to this are:
    • Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone.
    • Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen who are also be eligible for this study. 16. Has known history of, or any evidence of active, non-infectious pneumonitis. 17. Has an active infection requiring systemic therapy. 18. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator. 19. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 20. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. 21. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. 22. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). 23. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected). 24. Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.

    View trial on ClinicalTrials.gov


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    Published February 13, 2017
  • Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial of Infigratinib for the Adjuvant Treatment of Subjects With Invasive Urothelial Carcinoma With Susceptible FGFR3 Genetic Alterations (PROOF 302)

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    Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial of Infigratinib for the Adjuvant Treatment of Subjects With Invasive Urothelial Carcinoma With Susceptible FGFR3 Genetic Alterations (PROOF 302)


    Condition: Upper Tract Urothelial Carcinomas, Urothelial Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT04197986

    Sponsor: QED Therapeutics, Inc.

    Phase: Phase 3

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Key Inclusion Criteria:

    • 1. Are randomized within 120 days following nephroureterectomy, distal ureterectomy or cystectomy. 2. Have histologically or cytologically confirmed, invasive urothelial carcinoma with susceptible FGFR3 alterations. Variant histology is allowed provided urothelial carcinoma is predominant (>50%). Neuroendocrine (including small and large cell), sarcomatoid, and plasmacytoid variants are excluded (any component). 1. Regarding samples and documentation of FGFR3
    • i. FGFR3 mutation is confirmed if: FGFR3 gene is mutated in Exon 7 (R248C, S249C), Exon 10 (G370C, A391E, Y373C), or Exon 15 (K650M/T, K650E/Q) OR
    • ii. FGFR3 gene fusion or FGFR3 rearrangement is confirmed based on the following genomic criteria if:
    • Any fusion/rearrangement with a literature-derived known partner gene regardless of strand or frame.
    • Fusion/rearrangements in the same strand that are in frame with a novel partner gene.
    • Fusion/rearrangements with one breakpoint in the intron 17
    • exon 18 hotspot region and the other breakpoint in an intergenic region or another gene. This rule excludes 3' duplications comprising only exon 18.
    • iii. The amino acid numbers for the FGFR3 mutations refer to the functional FGFR3 isoform 1 (NP_000133.1) that is the NCBI Refseq ID used to report genetic alterations in FGFR3 by the FoundationOne® CDx test (F1CDx, Foundation Medicine, USA).
    • iv. FGFR3 alteration must be confirmed by Foundation Medicine for F1CDx testing:
    • The tumor sample to be used should be from the definitive surgical resection (cystectomy, nephroureterectomy, or distal ureterectomy), or from an archival biopsy of confirmed invasive urothelial carcinoma (≥pT2). 2. If status post neoadjuvant chemotherapy, pathologic stage at surgical resection must be Stage ≥ ypT2 and/or yN+. Prior neoadjuvant therapy is defined as at least 3 cycles of neoadjuvant cisplatin-based chemotherapy with a planned cisplatin dose of 70 mg/m2/cycle. Subjects who received less than this or non-cisplatin-based neoadjuvant treatment are not excluded. 3. If not status post neoadjuvant chemotherapy, is ineligible to receive cisplatin-based adjuvant chemotherapy based on Galsky criteria: 4. Subjects who refuse cisplatin-based chemotherapy or who are ineligible to receive cisplatin-based chemotherapy based on Galsky criteria must also meet the following criteria: 5. Must have a centrally reviewed negative postoperative computed tomography (CT) (defined as lymph nodes with short axis <1.0 cm and without growth and no distant metastases according to [RECIST v1.1 criteria or negative biopsy within 28 days before randomization to confirm absence of disease at baseline. 3. Have Eastern Cooperative Oncology Group (ECOG) performance status of ≤2. 4. If a woman of childbearing potential, must have a negative pregnancy test within 7 days of the first dose of study drug. Sexually active males must use a condom during intercourse while taking study drug and for 1 month after the last dose of study drug and should not father a child during this period

    Key Exclusion Criteria:

    1. Presence of positive invasive surgical margins following nephroureterectomy, distal ureterectomy, or cystectomy. In subjects not eligible for further surgery, radiotherapy, or other efficacious treatment, microscopic positive noninvasive margins (eg, carcinoma in situ) without gross residual disease are allowed.
    2. Have received Bacillus Calmette-Guerin (BCG) or other intravesical therapy for Non-Muscle Invasive Bladder Cancer (NMIBC) within the previous 30 days.
    3. Are currently receiving or are planning to receive during participation in this study, treatment with agents that are known moderate or strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration. Prior anticancer or other therapies are restricted as follows:
    4. Prior adjuvant treatment for urothelial cancer is not allowed.
    5. Prior neoadjuvant therapy (eg, chemotherapy, immunotherapy, or investigational) is allowed if inclusion criterion #4 is met. Prior neoadjuvant chemotherapy must have been completed within a period of time that is greater than the cycle length used for that treatment before first dose of study drug.
    6. Prior biologic, immunotherapy, or investigational therapy should have been completed within a period that is ≥5 half-lives or 30 days, whichever is shorter, before the first dose of study drug.
    7. Have previously or currently is receiving treatment with a mitogen-activated protein kinase (MEK) or selective FGFR inhibitor.
    8. Have a history of primary malignancy within the past 3 years other than (1) invasive UBC or UTUC (ie, disease under study), (2) noninvasive urothelial carcinoma, (3) any adequately treated in situ carcinoma or non-melanoma carcinoma of the skin, (4) any other curatively treated malignancy that is not expected to require treatment for recurrence during participation in the study, or (5) an untreated cancer on active surveillance that may not affect the subject's survival status for ≥3 years based on clinician assessment/statement and with medical monitor approval.
    9. Have current evidence of corneal keratopathy or retinal disorder confirmed by ophthalmic examination. Subjects with asymptomatic ophthalmic conditions assessed by the investigator to pose minimal risk for study participation may be enrolled in the study.
    10. Have a history and/or current evidence of extensive tissue calcification
    11. Have impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral infigratinib
    12. Have current evidence of endocrine alterations of calcium/phosphate homeostasis (eg, parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis), unless well controlled.
    13. Have consumed grapefruit, grapefruit juice, grapefruit hybrids, pomegranates, star fruits, pomelos, or Seville oranges or products containing juice of these fruits within 7 days before the first dose of study drug; have taken any Chinese herbal medicine or Chinese patent medicine treatments with anticancer activity within 14 days of the first dose of study drug.
    14. Have insufficient bone marrow function:
    15. Absolute neutrophil count (ANC) <1,000/mm3 (1.0 × 109/L).
    16. Platelets <75,000/mm3 (<75 × 109/L).
    17. Hemoglobin <8.5 g/dL; transfusion support is allowed if >1 week before randomization and hemoglobin remains stable.
    18. Have insufficient hepatic and renal function:
    19. Total bilirubin >1.5 × upper limit of normal (ULN) of the testing laboratory (for subjects with documented Gilbert syndrome, direct bilirubin must be ≤1.5 × ULN and enrollment requires approval by the medical monitor).
    20. AST/SGOT and ALT/SGPT >2.5 × ULN of the testing laboratory.
    21. Serum creatinine >1.5 × ULN or a calculated or measured creatinine clearance of <30 mL/min.
    22. Have amylase or lipase >2.0 × ULN.
    23. Have abnormal calcium or phosphorus:
    24. Inorganic phosphorus higher than 1.02 × ULN of the testing laboratory.
    25. Total serum calcium (can be corrected) higher than 1.02 × ULN of the testing laboratory.
    26. Have clinically significant cardiac disease including any of the following:
    27. New York Heart Association (NYHA) Class ≥2B; subjects with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the NYHA classification.
    28. Uncontrolled hypertension
    29. Presence of CTCAE v5.0 Grade ≥2 ventricular arrhythmias, atrial fibrillation, bradycardia, or conduction abnormality.
    30. Unstable angina pectoris or acute myocardial infarction ≤3 months before the first dose of study drug.
    31. Average QTcF >470 msec (males and females). Note: If the QTcF is >470 msec in the first ECG, a total of 3 ECGs separated by ≥5 minutes should be performed. If the average of these 3 consecutive results for QTcF is ≤470 msec, the subject meets eligibility in this regard.
    32. History of congenital long QT syndrome.
    33. Have had a recent (≤3 months before the first dose of study drug) transient ischemic attack or stroke.
    34. If female, are pregnant or nursing (lactating).

    View trial on ClinicalTrials.gov


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    Published May 20, 2020
  • Phase I Dose-Escalation Study of Image-Guided Radiation Therapy for Bladder-Cancer Patients Undergoing Radiotherapy and Concurrent Gemcitabine Chemotherapy

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    Phase I Dose-Escalation Study of Image-Guided Radiation Therapy for Bladder-Cancer Patients Undergoing Radiotherapy and Concurrent Gemcitabine Chemotherapy


    Condition: Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT01104350

    Sponsor: Memorial Sloan Kettering Cancer Center

    Phase: Phase 1

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • MSKCC-reviewed pathologically proven diagnosis of primary bladder urothelial carcinoma without evidence of regional (nodal) or distant spread (cT1-T4a, Nx or N0).
    • Karnofsky Performance Scale (KPS) ≥ 70%
    • Age ≥18 years old
    • Adequately functioning bladder, defined as continent and without the need for an indwelling catheter
    • Absolute neutrophil count (ANC) ≥ 1500/mL; platelets ≥ 100,000/mm3 serum bilirubin < 1.5 x the upper limit of normal (ULN); aspartate aminotransferase (AST) and/alanine aminotransferase (ALT) ≤ 1.5 × ULN
    • Adequate renal function: calculated creatinine clearance > 30 mL/min/1.73 m2 using the following formula modified Cockcroft and Gault Formula for estimated Creatinine Clearance
    • Patients must be considered able to tolerate systemic chemotherapy and pelvic radiation therapy.
    • Patients must have the ability to understand and the willingness to sign a written informed consent document

    Exclusion Criteria:

    • Evidence of distant disease or histologically-proven nodal metastases. Patients with radiologic evidence of lymphadenopathy must have biopsy proof of N0 status.
    • Previous pelvic radiation therapy
    • Prior systemic chemotherapy non-cisplatin based neoadjuvant for urothelial carcinoma (prior intravesical chemotherapy or immunotherapy is permissible)
    • Prior cisplatin based neoadjuvant systemic chemotherapy for more than >4 cycles
    • Active inflammatory bowel disease (i.e., Crohn's disease or ulcerative colitis)
    • Women who are pregnant or lactating

    View trial on ClinicalTrials.gov


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    Published December 12, 2016
  • Phase I Study of Hypofractionated Radiotherapy and Anti-PD1 Antibody (Pembrolizumab) in the Treatment of Advanced Bladder Cancer

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    Phase I Study of Hypofractionated Radiotherapy and Anti-PD1 Antibody (Pembrolizumab) in the Treatment of Advanced Bladder Cancer


    Condition: Invasive Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02560636

    Sponsor: Royal Marsden NHS Foundation Trust

    Phase: Phase 1

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    1. Histologically confirmed invasive bladder.carcinoma (T2-4,N0-3,M0-1).
    2. Be willing and able to provide written informed consent for the trial.
    3. Be ≥ 18 years of age on day of signing informed consent.
    4. Have measurable disease based on RECIST 1.
    5. , or, in group A, disease assessable by cystoscopic assessment.
    6. Have consented to analysis of tissue from an archival tissue sample
    7. Have a performance status of 0-1 on the ECOG Performance Scale.
    8. Planned for hypofractionated radiotherapy
    9. Demonstrate adequate organ function as defined in table 2 (please see protocol) all screening blood tests should be performed within 10 days of confirmation of eligibility.
    10. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to confirmation of study eligibility. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
    11. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
    12. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy if their partner has childbearing potential (as defined by not being surgically sterilized or have not been free from menses for > 1 year).

    Exclusion Criteria:

    • The subject must be excluded from participating in the trial if the subject: 1. Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment. 2. Previous pelvic radiotherapy, history of inflammatory bowel disease or other conditions that would in the opinion of the investigator would preclude the safe administration of pelvic radiotherapy. 3. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (>dose equivalent to 10mg of Prednisolone/day) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. 4. Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. 5. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent or therapy.
    • Note: Subjects with ≤ Grade 2 neuropathy or chemotherapy induced alopecia/nail changes are an exception to this criterion and may qualify for the study.
    • Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. 6. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, localized prostate cancer (≤T2 ≤ Gl3+4) or in situ cervical cancer that has undergone potentially curative therapy. Patients may have received treatment for previous urothelial malignancy. 7. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. 8. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study. 9. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis. 10. Has an active infection requiring systemic therapy. 11. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. 12. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 13. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. 14. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). 15. Has a known history of Human Immunodeficiency Virus (HIV). 16. Has known clinical history of Hepatitis B or Hepatitis C . 17. Has received a live vaccine within 30 days prior to the first dose of trial treatment.

    View trial on ClinicalTrials.gov


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    Published June 29, 2017
  • Phase II Study to Evaluate the Response to 2 Induction Courses (12 Intravesical Instillations) of Bacillus Calmette-Guérin (BCG) for High Risk Superficial Bladder Cancer

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    Phase II Study to Evaluate the Response to 2 Induction Courses (12 Intravesical Instillations) of Bacillus Calmette-Guérin (BCG) for High Risk Superficial Bladder Cancer


    Condition: Bladder Cancer, High Risk Superficial

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02281383

    Sponsor: Memorial Sloan Kettering Cancer Center

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Patients must have high risk non-muscle invasive urothelial bladder carcinoma (Tis, TaHG, or T1) that is pathologically confirmed by the Memorial Sloan Kettering Department of Pathology or a documented history of TaHG or T1 non-muscle invasive urothelial bladder tumors.
    • 18 years and older
    • All visible papillary lesions must be macroscopically resected within 60 days of treatment initiation.
    • Absence of urothelial carcinoma involving the upper urinary tract (documented by radiological imaging or biopsy) preferably within 12 months from the start of treatment. Should the imaging or biopsy be performed outside this window it will be up to the physicians discretion to re-scan/biopsy.
    • Patients who have received a single dose of mitomycin C following staging TUR.

    Exclusion Criteria:

    • Currently being treated or scheduled to have radiation treatment for bladder cancer during the study.
    • Treatment with intravesical BCG or chemotherapy for a patient's current
    • Currently being treated or scheduled to have treatment with any systemic or intravesical chemotherapeutic agent during the study.
    • Currently being treated with or having been treated in the last 12 months with any investigational drug for high risk superficial bladder cancer.
    • Previous muscle-invasive (i.e., stage T2 or higher) transitional cell carcinoma of the bladder.
    • Currently being treated for metastatic transitional cell carcinoma.
    • Scheduled to have surgery for bladder cancer during the study.
    • Presence of clinically significant infections or congenital or acquired immunodeficiency.

    View trial on ClinicalTrials.gov


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    Published June 29, 2017
  • Phase II Trial of Neoadjuvant Nivolumab With Cisplatin and Gemcitabine in Muscle-Invasive Bladder Cancer (MIBC) Patients Undergoing Radical Cystectomy

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    BLASST-1 (Bladder Cancer Signal Seeking Trial): Phase II Trial of Neoadjuvant Nivolumab With Cisplatin and Gemcitabine in Muscle-Invasive Bladder Cancer (MIBC) Patients Undergoing Radical Cystectomy


    Condition: Muscle Invasive Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03294304

    Sponsor: Masonic Cancer Center, University of Minnesota

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Diagnosis of MIBC (predominantly urothelial carcinoma) with clinical stage T2-T4a and N<1 disease (solitary lymph node measuring < 2 cm) and M0 and deemed eligible for radical cystectomy.
    • Age ≥ 18 years
    • ECOG Performance Status of 0 or 1.
    • Required initial laboratory values within 14 days of study enrollment:
    • Absolute Neutrophil Count ≥ 1500 cells/mm^3
    • Platelets ≥ 100,000 cells/mm^3
    • Hemoglobin ≥ 9.0 g/dL
    • Bilirubin ≤ 1.5 times the upper limit of normal (ULN) for the institution (For patients with known Gilbert's disease: bilirubin ≤ 3 x ULN)
    • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN for the institution
    • Creatinine clearance ≥ 50 ml/min by Cockcroft-Gault formula or 24 hour urinary clearance (CrCl = [140-age (years)] x actual weight (kg) / [72 x serum Cr (mg/dL)] (if patient is female multiply the above by 0.85) or 24 hour urinary creatinine clearance.
    • Alkaline phosphatase ≤ 2.5 x ULN for the institution
    • INR and aPTT ≤ 1.5 x ULN if not on therapeutic anticoagulation. Patients receiving therapeutic anticoagulation will be allowed if maintained on a stable dose.
    • Females of childbearing potential and males who are not surgically sterile and with partners of childbearing potential must agree to use effective contraception during study treatment for 5 months for females and 7 months for males after the last dose of nivolumab.
    • Ability to provide a signed and dated consent or have a legally authorized representative to provide written and signed consent prior to the initiation of any research related procedures.
    • Patient must agree to submission of archived tumor (20-25 formalin-fixed paraffin embedded (FFPE) slides of 5-10 microns in thickness) from TURBT and radical cystectomy tissues. If archived samples are not available fresh tissue will be used.
    • Ability to provide written consent prior to the initiation of any research related procedures.

    Exclusion Criteria:

    • Presence of N2-3 or M1 disease.
    • Ineligible to receive cisplatin by meeting one or more of the following criteria;
    • Creatinine clearance of < 50 mL/min
    • Hearing loss of 25 dB at two contiguous frequencies with testing required if a patient has hearing loss
    • At the investigator's discretion, and after discussion with the patient, this exclusion may be waived if the potential benefit of cisplatin therapy is felt to outweigh the risk of further hearing loss.
    • CTCAE v4 Grade 2 or higher peripheral neuropathy,
    • New York Heart Association Class III or IV heart failure
    • ECOG performance status 2 or higher.
    • Prior systemic therapy (intravenous) is not permitted. Prior intravesical therapies including intravesical gemcitabine is permitted for non-muscle invasive disease (i.e. T1 or lower).
    • Prior treatment with cisplatin for bladder cancer.
    • Prior treatment with anti-PD-1, CTLA-4, or anti-PD-L1 therapeutic antibody or pathway-targeting agents.
    • Prior therapeutic radiation to the bladder.
    • Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study.
    • Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, symptomatic congestive heart failure (>New York Heart Association Class 2), stroke, serious cardiac arrhythmia.
    • Human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related illness.
    • Pregnancy, lactation, or breast-feeding. Women of childbearing potential must have a negative urine pregnancy test at screening.
    • History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, Wegener's granulomatosis, vascular thrombosis associated with antiphospholipid syndrome, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, systemic vasculitis, or glomerulonephritis.
    • History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan, history of radiation pneumonitis in the radiation field (fibrosis) is permitted.
    • Active hepatitis B virus (HBV, chronic or acute, defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C antibody. Patients with past HBV infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBc Ab] and absence of HBsAg) are eligible. HBV DNA must be obtained in these patients prior to Cycle 1, Day 1 and confirmed to be negative. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
    • Active tuberculosis or BCG infection
    • Active infection requiring systemic antibiotics for more than 7 days within 3 days prior to Cycle 1, Day 1. Prophylactic short-term antibiotics will be allowed.
    • Administration of intravesical bacillus Calmette-Guerin (BCG) within 4 weeks before Cycle 1, Day 1
    • Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study.
    • Persisting toxicity from prior therapy (NCI CTCAE v4.03 Grade >1); however alopecia or other Grade <2 AEs not constituting a safety risk, based on Investigator's judgement, are acceptable.
    • History of or active bone marrow disorders expected to interfere with study therapy (e.g. acute leukemias, accelerated/blast-phase chronic myelogenous leukemia, chronic lymphocytic leukemia, Burkitt lymphoma, plasma cell leukemia, or non-secretory myeloma).
    • Prior allogeneic stem cell or solid organ transplant.
    • Known primary central nervous system (CNS) malignancy.
    • Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted but patients with psoriasis require a baseline ophthalmologic exam to rule out ocular manifestations. Rash must cover less than 10% of body surface area (BSA) and must be well controlled at baseline and only requiring topical steroids.
    • Any other chronic medical condition or psychiatric condition, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
    • Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin or in situ cervical cancer that has undergone potentially curative therapy. Patients on androgen deprivation therapy as part of adjuvant therapy after radiation for prostate cancer or patients on adjuvant hormonal therapies for breast cancer will be allowed if they are being considered for curative intent for bladder cancer.
    • Treatment with systemic immunostimulatory agents (including but not limited to interferon [IFN]-a or interleukin [IL]-2) within 4 weeks or five half-lives of the drug (whichever is shorter) prior to Cycle 1, Day 1
    • Concomitant use of systemic corticosteroids at physiologic doses or <10 mg/day of prednisone or equivalent.
    • Concomitant use of another investigational agent and/or treatment with an investigational agent within 4 weeks prior to Cycle 1, Day 1 (or within five halflives of the investigational product, whichever is longer).
    • Use of bisphosphonate therapy for osteoporosis will be allowed if started prior to study enrollment.

    View trial on ClinicalTrials.gov


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    Published September 28, 2017
  • Phase III Randomized Trial of Concurrent Chemoradiotherapy With or Without Atezolizumab in Localized Muscle Invasive Bladder Cancer (Study SWOG/NRG 1806)

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    Phase III Randomized Trial of Concurrent Chemoradiotherapy With or Without Atezolizumab in Localized Muscle Invasive Bladder Cancer


    Condition: Bladder Urothelial Carcinoma, Muscle Invasive Bladder Carcinoma, Stage II Bladder Cancer AJCC v8, Stage IIIA Bladder Cancer AJCC v8

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03775265

    Sponsor: National Cancer Institute (NCI)

    Phase: Phase 3

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • STEP 1 REGISTRATION: If this will be the first patient from a registering site to receive a given RT modality (3DCRT vs. IMRT), the site must first submit pre-RT planning documents within 3 days of Step 1 registration and receive approval from Imaging and Radiation Oncology Core (IROC) before randomizing the patient to Step 2. If this will not be the first patient to receive a specific RT modality, the patient should be immediately randomized to Step 2 on the same day.
    • STEP 2 RANDOMIZATION: If patient required review of pre-RT planning, randomization must occur within 14 days of initial registration.
    • Patients must have histologically proven, T2-T4a N0M0 urothelial carcinoma of the bladder within 120 days prior to randomization and no intervening treatment between the histologic proof and randomization. Patients with mixed urothelial carcinoma will be eligible for the trial, but the presence of small cell carcinoma will make a patient ineligible. Patients with lymph nodes >= 1.0 cm in shortest cross-sectional diameter on imaging (computed tomography [CT]/magnetic resonance imaging [MRI] of abdomen and pelvis) must have a biopsy of the enlarged lymph node showing no tumor involvement within 70 days prior to randomization. These patients may be suitable for neoadjuvant chemotherapy and radical cystectomy and are eligible for this trial if they seek out a bladder sparing treatment strategy, however patients who have received prior systemic chemotherapy for bladder cancer are not eligible for the trial.
    • Patients must undergo a transurethral resection of bladder tumor (TURBT) within 70 days prior to randomization. In a situation where a patient is referred from outside to the enrolling institution, patient must have a repeat office cystoscopy by the urologist who will be following the patient on the clinical trial to assess the adequacy of the prior TURBT. This cystoscopy can be performed in urologist office without general anesthesia. Patient may then undergo repeat TURBT if deemed necessary as standard of care by the treating urologist. Patients may have either completely or partially resected tumors as long as the treating urologist attempted maximal resection. Patient must not have T4b disease
    • Patients must undergo radiological staging within 70 days prior to randomization. Imaging of chest, abdomen, and pelvis must be performed using CT or MRI. Patients must not have evidence of T4bN1-3 disease. Eligibility is based on the local radiology report.
    • Patients with hydronephrosis are eligible if they have unilateral hydronephrosis and kidney function meets criteria specified.
    • Patients must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder within the previous 24 months except Ta/T1/carcinoma in situ (CIS) of the upper urinary tract including renal pelvis and ureter if the patient had undergone complete nephroureterectomy.
    • Patients must not have diffuse CIS based on cystoscopy and biopsy.
    • Patient must be planning to receive one of the protocol specified chemotherapy regimens.
    • All adverse events associated with any prior surgery and intravesical therapy must have resolved to Common Terminology Criteria for Adverse Events (CTCAE) grade =< 2 prior to randomization.
    • Patients must be >= 18 years of age
    • Patient must not have received any systemic chemotherapy for their bladder cancer.
    • Patient must not have had prior pelvic radiation.
    • Patients must not have received prior treatment for muscle invasive bladder cancer including neoadjuvant chemotherapy for the current tumor.
    • Patients must not have received any systemic therapy (including, but not limited to, interferon alfa-2b, high dose IL-2, pegylated interferon [PEG-IFN], anti-PD-1, anti-PD-L1), for non-muscle invasive bladder cancer. Prior intravesical bacillus Calmette-Guerin (BCG), interferon, and intravesical chemotherapy are allowed.
    • Patients must not have received any of the following prohibited therapies within 28 days prior to randomization or be planning to receive any of the following prohibited therapies during protocol treatment:
    • Anti-cancer systemic chemotherapy or biological therapy not specified in the protocol.
    • Immunotherapy not specified in this protocol.
    • Systemic or intravesical use of any non-study anti-cancer agent (investigational or non-investigational).
    • Investigational agents other than atezolizumab.
    • Live vaccines: Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, shingles, yellow fever, rabies, BCG, and typhoid (oral) vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. Flu-Mist) are live attenuated vaccines, and are not allowed. Prior administration of intravesical BCG is allowed.
    • Glucocorticoids for any purpose other than to modulate symptoms from an event of suspected immunologic etiology. The use of physiologic doses of corticosteroids (defined as 10 mg prednisone) are acceptable, however site investigators should consult with the study chair for any dose higher than 10 mg prednisone. Dexamethasone 4 mg IV with chemotherapy to prevent nausea is allowed.
    • RANKL infusion: Concurrent denosumab (which binds the cytokine RANKL) for any known indication is prohibited due to interaction with study medication.
    • Patients must not have a major surgical procedure within 28 days prior to randomization. If patient had any surgical procedure then they should have recovered to full presurgical performance status and surgical adverse events should have resolved to grade =< 2. TURBT is not considered a major surgical procedure.
    • Patients must not have received treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 14 days prior to randomization. Exceptions:
    • Patients may have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea).
    • The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed. Physiological doses equivalent of 10 mg prednisone daily are allowed. Short term steroids given as antiemetic therapy, e.g. 4 mg dexamethasone or equivalent once a week, is allowed.
    • Patients must not have received a live, attenuated vaccine within 4 weeks prior to randomization or anticipate that such a live, attenuated vaccine will be required while on protocol treatment and up to 5 months after the last dose of protocol treatment.
    • Inactivated influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine within 4 weeks prior to randomization or while on protocol treatment and up to 5 months after the last dose of protocol treatment.
    • Patients must not have undergone prior allogeneic bone marrow transplantation or prior solid organ transplantation.
    • Patient may or may not be radical cystectomy candidates.
    • Absolute neutrophil count (ANC) >=1,500/microliter (mcL) (within 28 days prior to randomization).
    • Platelets >= 100,000/mcL (within 28 days prior to randomization).
    • Hemoglobin >= 9 g/dL (within 28 days prior to randomization).
    • Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) (except patients with Gilbert's syndrome, who must have a total bilirubin < 3.0 mg/dL) (within 28 days prior to randomization).
    • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 x IULN (within 28 days prior to randomization).
    • Patients must not have clinically significant liver disease that precludes patient from treatment regimens prescribed on the study (including, but not limited to, active viral, alcoholic or other autoimmune hepatitis, cirrhosis or inherited liver disease).
    • Patients must have adequate renal function as evidenced by calculated creatinine clearance >= 25 mL/min. The creatinine used to calculate the clearance result must have been obtained within 28 days prior to randomization.
    • Patients must have Zubrod performance status =< 2.
    • Patients must have a baseline electrocardiography (ECG) performed within 30 days prior to randomization.
    • Patient must not have history of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis.
    • Patients must not have an active infection requiring oral or IV antibiotics within 14 days prior to randomization. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are not eligible. If patient develops urinary tract infection after TURBT they must have recovered from the infection prior to registration.
    • Patients must not have active autoimmune disease that has required systemic treatment in past two years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Autoimmune diseases include, but are not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, Graves' disease treated with methimazole or glomerulonephritis.
    • Patient must not have a history of active tuberculosis.
    • If patient has a known history of hepatitis B virus (HBV) or hepatitis C virus (HCV), they must meet the following criteria within 28 days prior to randomization.
    • Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible.
    • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA).
    • Patients who are known to be positive for human immunodeficiency virus (HIV) are eligible only if they have all of the following:
    • A stable regimen of highly active anti-retroviral therapy (HAART)
    • No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections
    • A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard PCR-based tests within 28 days prior to randomization.
    • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for two years. Patients with localized prostate cancer who are being followed by an active surveillance program are also eligible.
    • Female patients of childbearing potential must have a serum pregnancy test prior to randomization. Patients must not be pregnant or nursing due to the potential teratogenic side effects of the protocol treatment. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of protocol treatment, and for 5 months (150 days) after the last dose of all study drugs. A woman is considered to be of "reproductive potential" if she has had a menses at any time in the preceding 12 consecutive months.
    • Patients must not be known to be allergic to Chinese hamster egg or ovary cell products and must not have any known major allergic reactions to any study drug.
    • Patients must be offered the opportunity to participate in specimen banking for future studies.
    • Patients who can complete Patient-Reported Outcome instruments in English or Spanish must agree to complete the EORTC QLQ-C30, the EORTC QLQ-BLM30, the EPIC Bowel Assessment, and the EQ-5D-5L per protocol schedule of assessment.
    • As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.

    View trial on ClinicalTrials.gov


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    Published May 20, 2019
  • Pilot Study of Celecoxib Combined With Gemcitabine and Cisplatin for Neoadjuvant Treatment of Localized, Muscle-Invasive Bladder Cancer

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    Pilot Study of Celecoxib Combined With Gemcitabine and Cisplatin for Neoadjuvant Treatment of Localized, Muscle-Invasive Bladder Cancer


    Condition: Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02885974

    Sponsor: Baylor College of Medicine

    Phase: Phase 1

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Subjects or their legally authorized representative must be informed of the investigational nature of this study, and must sign and give written informed consent in accordance with institutional and federal guidelines.
    • Patients must have histologically proven urothelial carcinoma of the bladder. Those with mixed histology, including a component of urothelial carcinoma, are eligible. Pure small cell carcinoma, pure adenocarcinoma, and pure squamous cell carcinoma are excluded.
    • Patients must have Stage cT2-T4a N0 M0 disease. Clinical T stage is based on the TURBT sample, exam under anesthesia and cross-sectional imaging studies. Patients must undergo cystoscopy and TURBT as part of the staging procedure within 120 days prior to registration. To exclude non-bulky/low-risk tumors, subjects must have documented muscle invasion with at least one of the following: i. Disease measuring at least 10 mm on cross-sectional imaging. Bladder thickening on imaging, by itself, is not adequate. ii. The presence of tumor-associated hydronephrosis.
    • Patients must have staging scans with abdominal/pelvic CT or MRI scan, and CT scan or x-ray of the chest within 56 days prior to registration. If the alkaline phosphatase is > 1.5 x upper limit of normal (ULN), there is a presence of suspicious bone pain, or if there is other clinical suspicion of bone metastases, a whole body bone scan is required within 56 days prior to registration.
    • Patients must have a Zubrod performance status of 0, 1 or 2.
    • Patients must be 18 years of age or older.
    • Patients must have adequate renal function as evidenced by calculated creatinine clearance ≥ 50 mL/min. The serum creatinine value used in the calculation must have been obtained within 28 days prior to registration.
    • Patients must have adequate hepatic function (within 28 days prior to registration), defined as: i. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (or ≤ 2.5 x ULN with Gilbert's disease); and ii. SGOT (AST) ≤ 2 x institutional ULN; and iii. SGPT (ALT) ≤ 2 x institutional ULN.
    • Patients must have adequate hematologic function (within 28 days prior to registration), defined as: i. Absolute neutrophil count (ANC) ≥ 1,500/μL; and ii. Hemoglobin ≥ 9 g/dL; and iii. Platelets ≥ 100,000/μL.
    • Patients must have tumor tissues from transurethral resection of the bladder tumor (TURBT) that is within 120 days of registration and available for submission. Tissue sample must be sufficient for IHC testing; that is,it must be sufficient tumor tissues for correlative science after pathologic diagnosis [i.e., enough tumor tissue to pass the staging criteria in 4c].
    • Patients must consent to the submission of FFPE blocks and/or unstained slides.

    Exclusion Criteria:

    • Patients must not have received previous systemic cytotoxic chemotherapy for urothelial carcinoma.
    • Patients must not have peripheral neuropathy ≥ Grade 2.
    • Patients must not have presence of Class III or IV heart failure, according to New York Heart Association Classifications, or a known left ventricular ejection fraction of less than 50%. Note: LVEF evaluation by echocardiogram or multi-gated acquisition scan (MUGA) is not required prior to registration.
    • Patients must not have a significant history of bleeding events. Patients with a history of a significant bleeding episode (e.g. hemoptysis, upper or lower GI bleeding, grade 3 or 4 gross hematuria unable to be controlled by trans-urethral resection of the bladder tumor) within 6 months of registration are not eligible.
    • No arterial thrombotic events within 6 months of registration, including transient ischemic attack (TIA), cerebrovascular accident (CVA), peripheral arterial thrombus, unstable angina or angina requiring surgical or medical intervention in the past 6 months, or myocardial infarction (MI). Patients with clinically significant peripheral artery disease (i.e., claudication on less than one block) are ineligible. Patients who have experienced a deep venous thrombosis or pulmonary embolus within the past 6 months must be on stable therapeutic anticoagulation to be enrolled to this study.
    • In the opinion of the treating investigator, the patient must be a candidate to receive gemcitabine/cisplatin treatment.
    • Patients must not have aspirin sensitive asthma.
    • Patients must not be known to have hypersensitivity to cisplatin, gemcitabine, or celecoxib.
    • Patients must not have any incidence of or uncontrolled medical illness (e.g. active cardiac symptoms, active systemic infection, etc.) that would limit the patient's ability to participate in the protocol.
    • Patients must not be pregnant or nursing due to the potential teratogenic side effects of the protocol treatment. Women/men of reproductive potential must agree to use an effective contraceptive method during and for 6 months after completing protocol treatment. A negative pregnancy test is required within 7 days prior to registration for women of child-bearing potential.
    • Patients are ineligible if they plan on regular use of NSAIDs at any dose more than 2 times per week (on average) or aspirin at more than 325 mg at least three times per week, on average. Low-dose aspirin not exceeding 100 mg/day is permitted. Patients who agree to stop regular NSAIDs or higher dose aspirin are eligible and no wash out period is required.

    View trial on ClinicalTrials.gov


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    Published May 31, 2019
  • Prospective Cohort Study of Transurethral Resection of Bladder Tumor (TURBT) Combined With Adjuvant Intravenous GC Chemotherapy to Prevent Moderate-high Recurrence and Progression Risks of Muscle-invasive Bladder Cancer

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    Prospective Cohort Study of Transurethral Resection of Bladder Tumor (TURBT) Combined With Adjuvant Intravenous GC Chemotherapy to Prevent Moderate-high Recurrence and Progression Risks of Muscle-invasive Bladder Cancer


    Condition: Bladder Cancer, Gemcitabine and Cisplatin Chemotherapy, Epirubicin Instillation, Recurrence, Prognosis

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02716961

    Sponsor: The First Affiliated Hospital with Nanjing Medical University

    Eligibility:

    • Age: minimum 18 Years maximum 70 Years
    • Gender: All

    Inclusion Criteria:

    1. moderate-high risk non-muscle invasive bladder cancer patients: Multiple,recurrent, II-III grade, tumor diameter>3cm, invasive to submucosa, associated with carcinoma in situ.
    2. Normal liver and renal function.

    Exclusion Criteria:

    1. Liver and renal function deficiency (GFR<60ml/min*kg, ALT、AST>1.5*normal), lung function deficiency, heart failure, acute myocardial infarction, severe infection and trauma, major surgery and clinical hypotension and anaerobic conditions.
    2. Attending other drug experiments.
    3. Performance status, Zubrod-ECOG-WHO, ZPS≥
    4. Pregnant.
    5. Bone marrow transplantation, severe leukopenia, associated with severe infection or injury.

    View trial on ClinicalTrials.gov


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    Published June 29, 2017
  • Prospective Randomized Trial of Adjuvant Radiotherapy Following Surgery and Chemotherapy in Muscle Invasive Transitional Cell Carcinoma of Urinary Bladder

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    Prospective Randomized Trial of Adjuvant Radiotherapy Following Surgery and Chemotherapy in Muscle Invasive Transitional Cell Carcinoma of Urinary Bladder


    Condition: Bladder Cancer, Urothelial Carcinoma Bladder

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02951325

    Sponsor: Tata Memorial Centre

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • All patients should have undergone radical cystoprostatectomy for bladder cancer Patients with any of the below high risk features on histolopathology
    • Lymph Node positive with or without perinodal extension (PNE)
    • Cut-margin positive,
    • pT3 and pT4 disease,
    • Number of nodes dissected at surgery < 10 All patients irrespective of the final pathology if they have received neo-adjuvant chemotherapy prior to surgery for any of the following T3 T4 stage N1-3 stage No evidence of distant metastasis including para-aortic nodal metastasis KPS ≥ 70 Signed study specific consent form Adequate hepatic, renal and hematologic parameters

    Exclusion Criteria:

    • Contraindication to pelvic radiotherapy like inflammatory bowel disease
    • Uncontrolled diabetes or hypertension
    • Uncontrolled cardiac or respiratory co morbidity
    • Prior history of therapeutic irradiation to pelvis
    • Patient unwilling and unreliable for follow up and QoL

    View trial on ClinicalTrials.gov


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    Published June 29, 2017
  • Prospective Study of Bladder-Preservation Chemo-Radiotherapy (Partial Bladder Hypo-fractionated Radiotherapy) for Patients With Muscle-Invasive Bladder Cancer

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    Prospective Study of Bladder-Preservation Chemo-Radiotherapy (Partial Bladder Hypo-fractionated Radiotherapy) for Patients With Muscle-Invasive Bladder Cancer


    Condition: Infiltrating Bladder Urothelial Carcinoma

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02688348

    Sponsor: Jonsson Comprehensive Cancer Center

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Histologically confirmed muscle-invasive urothelial cancer (no histology will be excluded)
    • No pelvic nodal metastases or distant metastases (based on computed tomography [CT], positron emission tomography [PET] or magnetic resonance imaging [MRI])
    • Karnofsky performance status (KPS) >= 70
    • Ability to understand, and willingness to sign, the written informed consent
    • Patient will have either opted for bladder-sparing treatment as compared to radical cystectomy, or deemed medically inoperable
    • Following the recent recommendations from the International Consultation on Urological Diseases-European Association of Urology International Consultation on Bladder Cancer, eligible patients will be those with no hydronephrosis, no extensive carcinoma in situ (CIS), and no tumor invasion into the stroma of the prostate

    Exclusion Criteria:

    • Patients with any evidence of distant metastases
    • Prior pelvic radiotherapy
    • History of Crohn's disease or ulcerative colitis
    • Unable to receive chemotherapy
    • Histologies other than urothelial (eg. squamous cell carcinoma, adenocarcinoma, small cell)

    View trial on ClinicalTrials.gov


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    Published June 10, 2019
  • Randomised Controlled Multicenter Study.Effect of an Intensive Smoking- and/or Alcohol Cessation Intervention Placed Shortly Before and 5 Weeks After Bladder Cancer Surgery on Postoperative Complications

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    Randomised Controlled Multicenter Study.Effect of an Intensive Smoking- and/or Alcohol Cessation Intervention Placed Shortly Before and 5 Weeks After Bladder Cancer Surgery on Postoperative Complications


    Condition: Bladder Cancer, Smoking, Alcohol Consumption

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02188446

    Sponsor: Rigshospitalet, Denmark

    Eligibility:

    • Age: minimum 18 Years maximum 100 Years
    • Gender: All

    Inclusion Criteria:

    • Patients > 18 years scheduled for cystectomy due to bladder cancer
    • Daily smoker or/and intake of ->21 units (252 g) of alcohol pr week
    • Informed consent

    Exclusion Criteria:

    • Cancelled operation
    • Hypersensitivity to benzodiazepines, disulfiram or Nicotine replacement
    • Pregnant or breastfeeding women
    • Mentally incompetent patients

    View trial on ClinicalTrials.gov


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    Published June 29, 2017
  • Randomized Phase II Study of Neoadjuvant Nivolumab With and Without Urelumab in Patients With Cisplatin-Ineligible Muscle-Invasive Urothelial Carcinoma of the Bladder

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    Randomized Phase II Study of Neoadjuvant Nivolumab With and Without Urelumab in Cisplatin-Ineligible or Chemotherapy-refusing Patients With Muscle-Invasive Urothelial Carcinoma of the Bladder


    Condition: Urothelial Carcinoma, Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02845323

    Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Electively refusing cisplatin-based neoadjuvant chemotherapy or
    • Ineligible to receive cisplatin-based neoadjuvant chemotherapy based upon at least one of the following criteria:
    • Creatinine clearance < 60 ml/min
    • ECOG status =2
    • Grade > 2 hearing loss
    • Grade > 2 neuropathy
    • New York Heart Association Class III heart failure
    • Age ≥ 18 years old at time of consent
    • Patients must have the following laboratory values: a) Absolute neutrophil count (ANC) ≥ 1.5 K/mm3 (must be stable off any growth factor within 4 weeks of first study drug administration) b) Platelets ≥ 100 K/mm3 (transfusion to achieve this level is not permitted within 2 weeks of first study drug administration) c) Hemoglobin (Hgb) ≥ 9 g/dL d) Serum total bilirubin: ≤ 1.5 x ULN e) ALT and AST ≤ 3.0 x ULN f) Serum creatinine clearance (CrCl) ≥ 30 mL/min using the Cockcroft-Gault equation, see formula below:
    • CrCl = [140-age (years)] x weight (kg) / [72 x serum Cr (mg/dL)] (if patient is female multiply the above by 0.85)
    • Patients who give a written informed consent obtained according to local guidelines

    Exclusion Criteria:

    • Patients with locally advanced unresectable or metastatic urothelial carcinoma as assessed on baseline radiographic imaging obtained within 28 days prior to study registration. The required radiographic imaging includes: a) Abdomen/Pelvis
    • CT scan b) Chest
    • chest x-ray or CT scan
    • Patients with concurrent upper urinary tract (i.e. ureter, renal pelvis) invasive urothelial carcinoma.
    • Patients with another active second malignancy other than non-melanoma skin cancers and biochemical relapsed prostate cancer
    • Patients who have received the last administration of an anti-cancer therapy including chemotherapy, immunotherapy, and monoclonal antibodies ≤ 4 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy
    • Patients who have received prior therapy with immune checkpoint inhibitors (e.g. anti-PD-1, anti-PD-L1, anti-LAG3, anti-CTLA-4) or immune costimulatory molecules (e.g. anti-CD137, anti-OX40, anti-GITR) directed agents.
    • Patients who have had radiotherapy ≤ 4 weeks prior to starting study drug, or who have not recovered from radiotherapy toxicities
    • Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting study drug, or patients who have had minor procedures (i.e. TURBT), percutaneous biopsies or placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury
    • Patients with history of alcoholic or non-alcoholic steatohepatitis (NASH), auto-immune hepatitis, or previous grade 3-4 drug-related hepatitis. (Note: Patients with radiographic evidence of steatohepatitis are excluded unless a liver biopsy is obtained demonstrating no evidence of alcoholic or non-alcoholic steatohepatitis).
    • Patient with history of prior solid organ or allogeneic bone marrow transplant.
    • Patients with any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study: 1. Clinically significant cardiac diseases, including any of the following: i. History or presence of serious uncontrolled ventricular arrhythmias ii.Clinically significant resting bradycardia iii.Any of the following within 3 months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF), Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE) iv.Uncontrolled hypertension defined by a SBP ≥ 160 mm Hg and/or DBP ≥ 100 mm Hg, with or without anti-hypertensive medication(s) b) Cirrhosis, chronic active hepatitis or chronic persistent hepatitis c) Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory) d) Known diagnosis of any condition (i.e. post-hematopoietic or organ transplant, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, etc.) that requires chronic immunosuppressive therapy. Usage of non-steroidal anti-inflammatory medications (NSAIDS) for the treatment of osteoarthritis and uric acid synthesis inhibitors for the treatment of gout are permitted. For questions, please consult the study chair. e) Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol
    • Pregnant or breast-feeding women
    • Women of child-bearing potential, who are biologically able to conceive, and not employing two forms of highly effective contraception. Highly effective contraception must be used throughout the trial and up to 8 weeks after the last dose of study drug (e.g. male condom with spermicidal; diaphragm with spermicide; intra-uterine device). Women of child-bearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test ≤ 14 days prior to starting study drug
    • Fertile males not willing to use contraception, as stated above
    • Patients unwilling or unable to comply with the protocol

    View trial on ClinicalTrials.gov


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    Published November 30, 2017
  • Research on the Combined-Modality Treatment Model of Bladder Preservation in Muscular Invasive Bladder Cancer

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    Research on the Combined-Modality Treatment Model of Bladder Preservation in Muscular Invasive Bladder Cancer


    Condition: Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02861196

    Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

    Eligibility:

    • Age: minimum 18 Years maximum 75 Years
    • Gender: All

    Inclusion Criteria:

    1. bladder urothelium carcinoma
    2. cT2-4aN0M0
    3. life expectancy≥1 year
    4. ECOG PS 0-1
    5. have no previously received radiotherapy or chemotherapy
    6. have no major organ dysfunction
    7. have been provided informed written consent

    Exclusion Criteria:

    1. extensive carcinoma in situ or ureter invaded
    2. distant metastasis at primary diagnosis or lymphatic metastasis according to clinical diagnosis
    3. have severe major organ dysfunction
    4. cannot finish treatments because of other severe diseases or life expectance≤6 months
    5. exist other malignant tumors
    6. have severe coagulation disorders
    7. no other trails participated in 4 weeks

    View trial on ClinicalTrials.gov


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    Published October 9, 2017

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