Bladder Cancer

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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

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A Phase II Study of the Anti-PD-L1 Antibody MPDL3280A in Subjects With Non-metastatic Transitional Cell Carcinoma of the Bladder


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 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 CTLA-4, anti-PD1 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).

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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

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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.

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A Phase I, Open-label, Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of GSK3326595 in Subjects With Solid Tumors and Non-Hodgkin's Lymphoma


Condition: Neoplasms

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02783300

Sponsor: GlaxoSmithKline

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

  • Males and females >=18 years of age (at the time consent is obtained). For NHL cohort only, participants must be <=75 years of age at the time consent is obtained.
  • Capable of giving signed informed consent.
  • Able to swallow and retain orally-administered medication.
  • Eastern cooperative oncology group (ECOG) performance status of 0 to 2.
  • Diagnosis of one of the following:
  • Part 1: Histologically- or cytological-confirmed diagnosis of non-resectable or metastatic solid malignancy that has progressed on prior therapy (radiographic documentation of progression is adequate for study participation).
  • Part 2: Histologically- or cytologically-confirmed diagnosis of metastatic or non-resectable disease that has progressed on prior therapy (ACC tablet cohort does not require prior therapy for enrollment i.e. must be systemic therapy naive; for all tumors, (radiographic documentation of progression is adequate for study participation):
  • TNBC (estrogen receptor negative [ER-]/ progesterone receptor [PR-]/Human Epidermal Growth Factor Receptor 2 negative [Her2-], as defined by local laboratory standards);
  • ER+BC (estrogen receptor positive [ER+] or progesterone receptor positive [PR+], Her2-, as defined by local laboratory standards);
  • metastatic or non-resectable transitional cell carcinoma of the bladder, ureter, or renal pelvis;
  • recurrent GBM;
  • ACC requiring systemic therapy. In order to be eligible for enrolment, ACC participants must: have shown progression by local evaluation of scans, as per RECIST 1.1, within the 13 months prior to enrolment and have measurable disease, as confirmed by independent central review of baseline scans prior to first dose.
  • HPV-positive solid tumor of any primary histology.
  • NHL that is not one of the following subtypes, as determined by local laboratory testing: Burkitt's lymphoma or other high-grade lymphoma and double- or triple-hit large B-cell lymphoma.
  • NSCLC, of any histologic sub-type; with local mutational analysis demonstrating wild-type status of TP53 (i.e., p53 wild-type NSCLC).
  • Part 3: Histologically- or cytologically-confirmed diagnosis of metastatic or nonresectable NSCLC (of any histologic sub-type), metastatic transitional cell carcinoma of the urinary system (mTCC), squamous cell carcinoma of the head and neck (HNSCC), or melanoma that failed to respond to prior treatment with Programmed Cell Death-Protein 1 (PD-1) or Programmed Death-Ligand 1 (PD-L1) targeted therapy.
  • Prior therapy: ACC tablet cohort: participants must be systemic therapy-naïve. Prior surgery and/or radiation is permitted. NHL cohort: participants may have received up to 4 prior lines of systemic therapy for disease. Tumors with actionable mutations (e.g., BRAF V600E gene mutation in melanoma; Epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements in NSCLC) must have received prior therapy with targeted agents prior to enrollment. Apart from ACC tablet cohort, participants must have received at least one line of prior systemic therapy (or have a disease for which no approved therapy exists), and have no standard-of-care therapy that would be expected achieve a durable clinical response, or refuse standard therapy, or are not candidates for standard therapy.
  • Evaluable disease: During Part 1, evaluable disease is required; measurable disease per RECIST v1.1 is recommended but not required and Participants enrolled in Part 2 and Part 3 must demonstrate measurable disease per the disease-specific criteria.
  • PK/PD/biomarker/metabolite expansion cohort(s) only: Participants must consent to pre- and post-dose tumor biopsies and additional sample collection procedures.
  • Food effect and relative bioavailability sub-study only: Participants must consent to additional procedures.
  • Part 3 only: Participants must consent to additional procedures (including paired biopsies).
  • All prior treatment-related toxicities must be National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4 =
  • Adequate organ function as per Hematologic, Hepatic and Renal Laboratory Values.
  • Reproductive criteria:
  • A male participant with female partner of child bearing potential must agree to use one of the methods of contraception for the duration specified in protocol.
  • A female participant is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin [hCG] test), not nursing, and at least one of the following conditions apply: Reproductive potential: participants must agree to follow one of the options and the duration specified in protocol;
  • Non-reproductive potential defined as
  • i) Pre-menopausal females with one of the following: Documented tubal ligation, Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, Hysterectomy, Documented Bilateral Oophorectomy;
  • ii) Postmenopausal defined as 12 months of spontaneous amenorrhea with an appropriate clinical profile or females over 60 years of age. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment.

Exclusion Criteria:

  • Malignancy attributed to prior solid organ transplant.
  • Leptomeningeal disease, spinal cord compression, or brain metastases that require immediate central nervous system (CNS)-specific treatment in the opinion of the Investigator (e.g., for symptomatic disease).
  • Recent prior therapy, defined as
  • 1. Any non-monoclonal anti-cancer therapy within 14 days or 5 half-lives, whichever is longer, prior to the first dose of GSK3326595. Any nitrosoureas or mitomycin C within 42 days prior to the first dose of GSK3326595. Prior therapy with biologic agents (including monoclonal antibodies) is permitted so long as 28 days have elapsed since therapy and all therapy-related AEs have resolved to =
  • 2. Any radiotherapy within 14 days or major surgery within 28 days prior to the first dose of GSK3326595. For participants in the GBM cohort, participants must have completed radiation therapy at least 28 days prior to the first dose of GSK3326595.
  • 3. Anti-androgen therapies for prostate cancer, such as bicalutamide, must be stopped 4 weeks prior to enrollment. Second-line hormone therapies such as enzalutamide or abiraterone should be stopped 2 weeks prior to enrolment. Participants with prostate cancer should remain on luteinizing hormone releasing hormone (LHRH) agonists or antagonists. Participants with prostate cancer may also remain on low-dose prednisone or prednisolone (up to 10 mg/day) and still be eligible for this study.
  • Part 3 only: History of any of the following: Recent history (within the past 2 years) of autoimmune disease or syndrome that required systemic treatment; a diagnosis of immunodeficiency or administration of systemic steroids (>=10 mg oral prednisone or equivalent) or other immunosuppressive agents within 7 days prior to randomization; Receipt of any live vaccine within 30 days prior randomization; Prior allogeneic/autologous bone marrow or solid organ transplantation; Current pneumonitis or history of non-infectious pneumonitis that required steroids or other immunosuppressive agents; Recent history of allergen desensitization therapy within 4 weeks of randomization; History of severe hypersensitivity to monoclonal antibodies.
  • History of a second malignancy, excluding non-melanoma skin cell cancer within the last three years. Participants with second malignancies that were indolent, in situ or definitively treated may be enrolled even if less than three years have elapsed since treatment. Consult the GSK Medical Monitor if second malignancies meet the requirements specified above.
  • Current use of a prohibited medication or planned use of any forbidden medications during treatment with GSK3326595.
  • Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, renal, cardiac disease, or clinically significant bleeding episodes). Any serious and/or unstable pre-existing medical (aside from malignancy), psychiatric disorder, or other conditions that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures, in the opinion of the Investigator.
  • Any clinically significant gastrointestinal (GI) abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach and/or bowels.
  • History of known human immunodeficiency virus (HIV) infection or positive HIV test result at screening.
  • Presence of hepatitis B surface antigen (HBsAg) or positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment. Participants with positive Hepatitis C antibody due to prior resolved disease can be enrolled only if a confirmatory negative Hepatitis C Ribonucleic acid (RNA) polymerase chain reaction (PCR) is obtained.
  • Any of the following cardiac abnormalities: 1. Recent history (within 6 months of first dose of study drug) of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting. 2. Presence of a cardiac pacemaker, 3. Baseline QTcF >=450 millisecond, 4. Uncontrolled arrhythmias. Participants with rate-controlled atrial fibrillation for >1 month prior to first dose of study drugs may be eligible. 5. Class II, III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
  • History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.

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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.

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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

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Molecular Correlates of Sensitivity and Resistance to Therapy in Genitourinary Malignancy


Condition: Localized Renal Pelvis and Ureter Urothelial Carcinoma, Malignant Solid Neoplasm, Metastatic Malignant Neoplasm in the Bone, Metastatic Malignant Neoplasm in the Soft Tissues, Metastatic Renal Pelvis and Ureter Urothelial Carcinoma, Recurrent Bladder Carcinoma, Recurrent Prostate Carcinoma, Recurrent Renal Pelvis and Ureter Urothelial Carcinoma, Stage IV Bladder Cancer AJCC v7, Stage IV Bladder Urothelial Carcinoma AJCC v7, Stage IV Prostate Cancer AJCC v7

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT01050504

Sponsor: University of Washington

Phase:

Eligibility:

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

Inclusion Criteria:

  • Patients with localized and/or metastatic bladder/urothelial or prostate cancer who have disease in the primary organ, biopsy accessible bone metastases (collaborating radiologists will determine if bone metastasis is appropriate for biopsy) or soft tissue metastases are eligible; men and women without cancer are eligible to have blood or normal tissue collected if acquired as part of non-research procedures (e.g. transurethral resection of the prostate or bladder); in patients without malignancy, no additional tissue beyond that necessary for care will be procured
  • Ability to adequately understand and give informed consent
  • Local or metastatic disease to soft tissue or bone at sites accessible to biopsy with minimal risk of complications Or the ability to obtain tissue with minimal risk of complication from a surgical procedure being conducted as a part of another research study Or for standard of care purposes or patients who have archival tissue collected for research or standard of care who are willing to donate archival tissue for this study
  • Alternatively, men and women without cancer or who are at risk of developing cancer are eligible to have blood or normal tissue collected if acquired; tissue will only be acquired as part of non-research procedures (e.g. transurethral resection of the prostate or bladder; in patients without malignancy, no additional tissue beyond that necessary for care will be procured
  • Platelet count > 50,000
  • White blood cell (WBC) > 1,500
  • Hemoglobin (Hgb) > 8.0
  • International normalized ratio (INR) < 1.5
  • Partial thromboplastin time (PTT) < 45
  • No history of excessive unexplained bleeding from previous surgery

Exclusion Criteria:

  • Patients unable to stop chronic anticoagulation with warfarin or Lovenox for less than 3 days
  • Serious or uncontrolled infection
  • Treatment with a vascular endothelial growth factor (VEGF) inhibitor (such as Avastin) within the past 28 days

View trial on ClinicalTrials.gov


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A Genotype-Phenotype Urothelial Cancer Registry


Condition: Urothelial Cancer, Renal Pelvis Cancer, Ureter Cancer, Bladder Cancer

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT00902590

Sponsor: Memorial Sloan Kettering Cancer Center

Phase:

Eligibility:

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

Inclusion Criteria:

  • Urothelial Cancer Cases
  • Must be ≥ 18 years of age AND
  • Must have a diagnosis of urothelial cancer AND
  • Must be an English-speaker Non-Cancer Control Group
  • Must be ≥ 18 years of age AND
  • Must not have cancer or a personal history of cancer, with the exception of skin cancer. AND
  • Must not be a blood relative of cases AND
  • Must not be a blood relative of another control AND
  • Must be an English-speaker Family Member Control Group: In select kindreds with a high prevalence of bladder cancer and/or very early onset bladder cancer, first- and second-degree family members of probands may be contacted by the MSKCC study team and invited to complete the questionnaire and submit a saliva sample.
  • Must be ≥ 18 years of age AND
  • Must be a blood relative of a case participant AND
  • Must be an English-speaker

Exclusion Criteria:

  • Have any condition, which in the opinion of the primary MSKCC clinician or investigators precludes their ability to provide informed consent.

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Neoadjuvant Chemotherapy Versus Surgery Alone in Patients With High-Grade Upper Tract Urothelial Carcinoma


Condition: High-Grade Upper Tract Urothelial Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02876861

Sponsor: Xiangya Hospital of Central South University

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Histologically confirmed high-grade upper tract transitional cell carcinoma at MSKCC or a participating site 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.
  • Medically appropriate candidate for radical nephroureterectomy or ureterectomy as per MSKCC or a participating site attending urologic oncologist
  • Karnofsky Performance Status ≥ 70%
  • Age ≥ 18 years of age
  • Required Initial Laboratory Values: Absolute neutrophil count ≥ 1500 cells/mm3 Platelets ≥ 100,000 cells/mm3 Hemoglobin ≥ 9.0g/dL Bilirubin ≤ 1.5 Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN for the institution Alkaline phosphatase ≤ 2.5 x upper limit of normal (ULN) for the institution Serum creatinine ≤ 1.5 mg/dL and calculated creatinine clearance ≥ 55 If female of childbearing potential, serum pregnancy test is negative.
  • Patients with reproductive potential must use an effective method to avoid pregnancy for the duration of the trial. ml/min/1.73m2 using the formula: Chronic kidney disease (CKD) epi : glomerular filtration rate (GFR) = 141 X min(Scr/κ,1)α X max(Scr/κ,1)-1.209 X 0.993 Age X 1.018 [if female] X 1.159 [if black]
  • Scr is serum creatinine, k is 0.7 for females and 0.9 for males, a is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/k or 1, and max indicates the maximum of Scr/k or 1.
  • If female of childbearing potential, serum pregnancy test is negative.
  • Patients with reproductive potential must use an effective method to avoid pregnancy for the duration of the trial

Exclusion Criteria:

  • Concomitant bladder urothelial carcinoma is acceptable if it is organ confined and surgically resectable.
  • Presence of carcinoma in situ (CIS)
  • Prior systemic chemotherapy (prior intravesical therapy is allowed)
  • Prior radiation therapy to the bladder
  • Evidence of New York Heart Association (NYHA) functional class III or IV heart disease.
  • Serious intercurrent medical or psychiatric illness, including serious active infection.
  • Preexisting sensory grade 3 neuropathy
  • Major surgery or radiation therapy < 4 weeks of starting study treatment.
  • Concomitant use of any other investigational drugs
  • Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism.
  • Ongoing cardiac dysrhythmias of NCI CTCAE Version 4.0 grade ≥ 2.
  • Uncontrolled hypertension (>150/100 mmHg despite optimal medical therapy).
  • Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection. Patients with HIV but no evidence of AIDS will be considered candidates.
  • Concurrent treatment on another clinical trial involving an intervention which may affect the primary endpoint. Supportive care trials or non-treatment trials, e.g. QOL, are allowed.
  • Ongoing treatment with therapeutic doses of warfarin or low molecular weight heparin (low dose warfarin up to 2 mg po daily or use of subcutaneous low molecular weight heparin for thromboembolic prophylaxis is allowed).
  • Pregnancy or breast-feeding. Patients must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the MSKCC and participating site PI. Male patients must be surgically sterile or agree to use effective contraception

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A Phase 3 Study of Erdafitinib Compared With Vinflunine or Docetaxel or Pembrolizumab in Subjects With Advanced Urothelial Cancer and Selected FGFR Gene Aberrations


Condition: Urothelial Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03390504

Sponsor: Janssen Research & Development, LLC

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  • Histologic demonstration of transitional cell carcinoma of the urothelium. Minor components ( less than [<] 50 percent [%] overall) of variant histology such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or micropapillary change are acceptable
  • Metastatic or surgically unresectable urothelial cancer
  • Documented progression of disease, defined as any progression that requires a change in treatment, prior to randomization
  • Cohort 1: Prior treatment with an anti-PD-(L) 1 agent as monotherapy or as combination therapy; no more than 2 prior lines of systemic treatment. Cohort 2: No prior treatment with an anti-PD-(L) 1 agent; only 1 line of prior systemic treatment. Subjects who received neoadjuvant or adjuvant chemotherapy and showed disease progression within 12 months of the last dose are considered to have received systemic therapy in the metastatic setting.
  • A woman of childbearing potential who is sexually active must have a negative pregnancy test (beta human chorionic gonadotropin [beta hCG]) at Screening (urine or serum)
  • Participants must meet appropriate molecular

Eligibility Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status Grade 0, 1, or 2
  • Adequate bone marrow, liver, and renal function

Exclusion Criteria:

  • Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 30 days prior to randomization
  • Active malignancies (that is, requiring treatment change in the last 24 months). The only allowed exceptions are: urothelial cancer, skin cancer treated within the last 24 months that is considered completely cured, localized prostate cancer with a gleason score of 6 (treated within the last 24 months or untreated and under surveillance) and localized prostate cancer with a gleason score of 3+4 that has been treated more than 6 months prior to full study screening and considered to have a very low risk of recurrence.
  • Symptomatic central nervous system metastases
  • Received prior fibroblast growth factor receptor (FGFR) inhibitor treatment
  • Known allergies, hypersensitivity, or intolerance to erdafitinib or its excipients
  • Current central serous retinopathy (CSR) or retinal pigment epithelial detachment of any grade.
  • History of uncontrolled cardiovascular disease
  • Impaired wound healing capacity defined as skin/decubitus ulcers, chronic leg ulcers, known gastric ulcers, or unhealed incisions

View trial on ClinicalTrials.gov


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