Bladder Cancer

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Pilot Study of Atezolizumab Plus PGV001, a Multipeptide Personalized Neoantigen Vaccine, in Patients With Locally Advanced or Metad or Metastatic Urothelial Cancer


Condition: Urothelial/Bladder Cancer, Nos

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03359239

Sponsor: Matthew Galsky

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

  • Written informed consent and HIPAA authorization for release of personal health information.
  • Age ≥ 18 years at the time of consent.
  • ECOG Performance Status of ≤ 1 within fourteen days of registration for protocol therapy.
  • Histological or cytological evidence of urothelial cancer of the bladder, urethra, ureter, or renal pelvis. Differentiation with variant histologies (e.g., squamous cell differentiated) or pure variant histologies will be permitted provided that the predominant histology is urothelial carcinoma.
  • Clinical disease state specific criteria:
  • Subjects with invasive urothelial cancer of the bladder or upper urinary tract may consent either before or within 6 weeks after radical cystectomy or nephroureterectomy.
  • Subjects with metastatic and/or unresectable disease must have a metastatic site amenable to biopsy. In situations where a metastatic biopsy does not yield sufficient genetic material for sequencing, or a biopsy cannot be feasibly performed, the use of archival tumor tissue may be considered on a case by case basis. The archival tissue must be derived from a muscle-invasive urothelial cancer specimen or metastatic urothelial cancer specimen.
  • Required laboratory values must be obtained within thirty days of consent.
  • ANC ≥ 1500 cells/µL
  • WBC counts > 2500/µL
  • Lymphocyte count ≥ 300/µL
  • Platelet count ≥ 100,000/µL
  • Hemoglobin ≥ 8.0 g/dL
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) with the following exception: o Patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN may be enrolled.
  • AST and ALT ≤ 3.0 x ULN with the following exception: o Patients with liver involvement: AST and/or ALT ≤ 5 x ULN
  • Alkaline phosphatase ≤ 2.5 x ULN with the following exception: o Patients with documented liver involvement or bone metastases: alkaline phosphatase ≤ 5 x ULN
  • Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 30 mL/min on the basis of the Cockcroft-Gault glomerular filtration rate estimation:
  • (140
  • age) x (weight in kg) x (0.85 if female) / 72 x (serum creatinine in mg/dL)
  • INR and aPTT ≤ 1.5 x ULN o This applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation (such as low-molecular-weight heparin or warfarin) should be on a stable dose. Exclusion Criteria:
  • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
  • Symptomatic CNS metastases and/or metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm) and/or history of intracranial hemorrhage or spinal cord hemorrhage
  • Pregnancy, lactation, or breastfeeding
  • Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • History or risk of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis
  • Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible.
  • Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible.
  • Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
  • 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 o History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  • History of HIV infection or active hepatitis B (chronic or acute) or hepatitis C infection
  • Active tuberculosis
  • A known additional primary malignancy that is progressing or requires active treatment. Exceptions include cancers that have undergone potentially curative therapy.
  • Medication-Related Exclusion Criteria:
  • Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway targeting agents
  • No history of severe immune-related adverse effects from anti-CTLA 4 (NCI CTCAE Grade 3 and 4)
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation Please contact site for other inclusion/

Exclusion Criteria:

  • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
  • Symptomatic CNS metastases and/or metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm) and/or history of intracranial hemorrhage or spinal cord hemorrhage
  • Pregnancy, lactation, or breastfeeding
  • Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • History or risk of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis
  • Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible.
  • Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible.
  • Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
  • 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 o History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  • History of HIV infection or active hepatitis B (chronic or acute) or hepatitis C infection
  • Active tuberculosis
  • A known additional primary malignancy that is progressing or requires active treatment. Exceptions include cancers that have undergone potentially curative therapy.
  • Medication-Related Exclusion Criteria:
  • Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway targeting agents
  • No history of severe immune-related adverse effects from anti-CTLA 4 (NCI CTCAE Grade 3 and 4)
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation Please contact site for other inclusion/exclusion criteria.

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Adjuvant Radiotherapy in Patients With Pathological High-risk Bladder Cancer: A Randomized Multicentre Phase II Study


Condition: Patients With High-risk MIBC

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03333356

Sponsor: UNICANCER

Eligibility:

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

Inclusion Criteria:

  1. To be eligible, the patients must fulfil all of the following inclusion criteria:
  2. Patients with histologically-confirmed muscle-invasive bladder cancer, either with pure urothelial carcinomas, or dominant urothelial carcinomas (>50%) combined with other histological variants including: micropapillary, epidermoid, or adenocarcinomas, are eligible. Patients with small cell variants, pure adenocarcinomas, or pure epidermoid carcinomas are not eligible.
  3. Patients with radical cystectomy and pelvic lymph nodes dissection with no microscopic residual disease (R0 and R1). Note that only R1 patients without urinary diversion as orthotropic neo-bladder replacement are eligible for the study, to limit cystectomy bed radiation induced toxicities.
  4. Patients with tumours of TNM staging: pN0-2, M0 by imagery, and pT3a, pT3b, pT4a, and pT4b, as well as, pTX-pN1-2, pTX-NX-R1 are eligible.
  5. Patients having received neo-adjuvant or adjuvant chemotherapy treatment are eligible. Randomization is allowed only if AE due to chemotherapy are ≤grade 2 at randomization.
  6. Patients ≥18 years old.
  7. Eastern Cooperative Oncology Group (ECOG) performance status ≤
  8. Absolute neutrophil count (ANC) ≥1500 cells/mm³.
  9. Platelets ≥100000 cells/mm³.
  10. Haemoglobin ≥8 g/dL (Note: following a blood transfusion or another intervention if required).
  11. Adequate hepatic function: aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) ≤2.5 x upper limit of normal (ULN); or ≤3.5 x ULN in the case of concurrent disease with known etiology and for which a corrective treatment is possible.
  12. Adequate renal function: clearance >30 mL/min (MDRD).
  13. Patients having provided written informed consent prior to any study-related procedures.
  14. Patients affiliated to the social security scheme.
  15. Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.

Exclusion Criteria:

  • Patient must not be enrolled if he/she fulfils any of the following non-inclusion criteria: 1. Patients with R1 resection and with orthotropic neo-bladder reconstruction as urinary diversion are not eligible. 2. Patients with clinical or radiological evidence of metastases or N3 staged bladder cancer are not eligible. 3. Prior invasive solid tumours or haematological malignancies unless disease free for a minimum of 3 years prior to randomisation except:
  • skin basal cell carcinoma,
  • in situ epithelioma of the cervix,
  • or prostate cancer: incidentally discovered during cystoprostatectomy and pelvic lymph node dissection and with a good prognosis (T stage
  • Unstable angina or congestive heart failure that required hospitalization in the 6 months before randomisation.
  • Transmural myocardial infarction in the 6 months prior to randomisation.
  • Acute bacterial or fungal infection requiring intravenous antibiotics at randomisation.
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of randomisation.
  • Severe hepatic disease: Child-Pugh Class B or C hepatic disease.
  • Known acquired immune deficiency syndrome (AIDS); the study treatment could impact blood count. 9. Patients with any other disease or illness which requires hospitalization or is incompatible with the study treatment are not eligible. 10. Patients unable to comply with study obligations for geographic, social, or physical reasons, or who are unable to understand the purpose and procedures of the study. 11. Patients enrolled in another therapeutic study within 30 days prior of randomisation. 12. Person deprived of their liberty or under protective custody or guardianship.

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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.

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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

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A Randomized Placebo Controlled Phase I/II Study Evaluating the Safety and Efficacy of alpha1H in Adult Patients With Non-muscle Invasive Bladder Cancer Awaiting Transurethral Surgery


Condition: Non-muscle Invasive Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03560479

Sponsor: Hamlet Pharma AB

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

  • Patient with non-muscle invasive papillary bladder cancer (NMIBC) based on cystoscopy appearance, on the waiting list for TURB.
  • Negative pregnancy test in women of childbearing potential.
  • Appropriate methods of contraception in women of childbearing potential during study.
  • Patients should be able to keep the content of the bladder for at least one hour.

Exclusion Criteria:

  • Patient with a previous history of muscle invasive bladder cancer.
  • Patient with a history of NMIBC with an interval shorter than 6 months after previous TURB.
  • Previous intravesical Bacillus Calmette-Guerin (BCG) immunotherapy in the last 12 months.
  • Previous intravesical chemotherapy in the last 12 months.
  • Participants with any other cancer diagnosis within the last 5 years (except of skin basaliomas).
  • Acute urinary tract infection
  • Participants with prior radiotherapy or systemic chemotherapy.
  • Participants receiving any other investigational agent or non-marketed product one month prior to Visit 1 and during the trial.
  • Any concurrent illness that may render a participant ineligible or limit compliance with study requirements.
  • Previously enrolled in this trial.

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Influence of Hormone Treatment in Radiation Therapy for Bladder Cancer


Condition: Bladder Cancer, Radiation Therapy Complication, Quality of Life

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT04282876

Sponsor: Aarhus University Hospital

Phase:

Eligibility:

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

Inclusion Criteria:

  • T2-T4 bladder cancer
  • radiation therapy
  • able to fill out questionnaires
  • signed informed consent

Exclusion Criteria:

  • KAD prior to TUR-B
  • dementia or other cognitive impairment
  • metastatic disease

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Evaluation of the Xpert® Bladder Cancer Monitor Assay Compared to Cystoscopy for the Follow-up of Patients With History of Low or Intermediate Risk Non-muscle-invasive Bladder Cancer (NMIBC): an Observational Prospective International Multicenter Study


Condition: Non-muscle-invasive Bladder Cancer

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT03664258

Sponsor: Cepheid

Phase:

Eligibility:

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

Inclusion Criteria:

  • Patient undergoing a follow-up cystoscopy at the time of enrolment for low or intermediate risk NMIBC patients in the follow-up phase (according to the 2017 EAU guidelines),
  • Patient must accept to be followed for 1 year after enrolment cystoscopy,
  • Patient who can provide urine samples naturally (e.g. no catheterization),
  • 18 years or older at the time of enrolment,
  • Signed informed consent.

Exclusion Criteria:

  • Patient with history of NMIBC stratified at the time of enrolment as high risk according to 2017 EAU Guidelines,
  • Patient with history of Muscle-Invasive Bladder Cancer (MIBC),
  • Patient having undergone a TURB less than 3 months before enrolment,
  • Patient having received Mitomycin C (MMC) or Bacillus Calmette-Guerin (BCG) intravesical instillations less than 3 months before enrolment (a single MMC post-operative instillation is acceptable for inclusion).

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A Phase II Clinical Study of Intravesical Photodynamic Therapy in Patients With BCG-Unresponsive Non-Muscle Invasive Bladder Cancer ("NMIBC") Or Patients Who Are Intolerant to BCG Therapy ("Study").


Condition: Non-Muscle Invasive Bladder Cancer (NMIBC) Refractory to BCG

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03945162

Sponsor: Theralase Inc.

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • 1. Be willing and able to provide a written Informed Consent Form ("ICF") for the Study. 2. Be > 18 years of age on day of signing ICF. 3. Have histologically confirmed NMIBC CIS with or without resected papillary disease (Ta, T1) (high grade) according to the 2004 World Health Organization ("WHO") / International Society of Urologic Pathology classification system up to 8 weeks prior to the treatment procedure. • Confirmation of histology, grade and stage will be performed by local review and must be completed prior to enrolment. 4. Patients with Ta, or T1 disease, must have undergone complete Trans-Urethral Resection of the Bladder Tumour ("TURBT") defined as the absence of resectable disease after at least 1 cystoscopy or TURBT procedure. • The most recent cystoscopy must have been performed no longer than 8 weeks prior to the treatment procedure. 5. Considered BCG-Unresponsive, which is at least one of the following:
  • At least five of six doses of an initial induction course, plus at least two of three doses of maintenance therapy
  • At least five of six doses of an initial induction course, plus at least two of six doses of a second induction course
  • Patients experiencing disease relapse less than 12 months after finishing the second course of BCG therapy are also considered BCG-Unresponsive. 6. Are not candidates for cystectomy on medical grounds or refuse radical cystectomy. 7. Have an Eastern Cooperative Oncology Group ("ECOG") performance score of 0 to 1. 8. Have satisfactory bladder function. Ability to retain Study Drug for a minimum of 1 hour. 9. Are available for the duration of the Study including follow-up (approximately 12 months). 10. Female patients of childbearing potential must have a negative Human Chorionic Gonadotropin ("HCG") pregnancy test taken during the screening visit and confirmed prior to the treatment procedure. 11. Female patients of childbearing potential must be willing to use 2 methods of birth control (i.e.: oral contraceptive, pills, diaphragm or condoms) or be surgically sterile, or abstain from heterosexual activity for two weeks after the treatment procedure. Patients of childbearing potential are those who have not been surgically sterilized or have not been free from menses for >1 year. 12. Intolerance of BCG therapy

Exclusion Criteria:

  1. Past or current muscle invasive (i.e.: T2, T3, T4) or metastatic urothelial carcinoma.
  2. Has concurrent extravesical (i.e.: urethra, ureter, renal pelvis, prostate or prostatic ducts) non-muscle invasive transitional cell carcinoma of the urothelium. (confirmed by staging to exclude extravesical disease, which may include radiological imaging and/or biopsy) within 3 months of enrollment: If previous work up occurred more than 3 months prior to enrollment, staging for extravesical disease must be repeated prior to enrolment in order to determine eligibility.
  3. Active gross hematuria.
  4. Have 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 that has undergone potentially curative therapy, in situ cervical cancer or localized prostate cancer under active surveillance with Gleason 6 disease. A history of prostate cancer that was treated with definitive intent (surgically or through radiation therapy) is acceptable, provided that the following criteria are met: Stage T2N0M0 or lower; prostate-specific antigen (PSA) undetectable for 2 years while off androgen deprivation therapy or no more than 2 consecutive rising PSAs.
  5. Have a history or current evidence of any condition, therapy, surgery or laboratory abnormality that, in the opinion of the PI, might confound the results of the Study, interfere with the patient's participation in the Study, or is not in the best interest of the patient to participate.
  6. Currently receiving treatment with a prohibited concomitant therapy (refer to 12.2.1, Prohibited Medications).
  7. Participated in a study with an investigational agent or device within 1 month from the first dose of current Study treatment.
  8. Prior treatment with an intravesical chemotherapeutic agent within 1 month of the first dose of current Study Drug, with the exception of a single perioperative dose of chemotherapy immediately post-TURBT (not considered treatment).
  9. Have an active infection requiring systemic therapy, including active or intractable Urinary Tract Infection ("UTI"), not resolved prior to the procedure.
  10. Has any contraindication to general or spinal anesthesia.
  11. Is pregnant or breastfeeding within the projected duration of the Study, starting with the screening visit through to two weeks following the second TLD-1433 instillation.

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A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatments and Combinations in Patients With Urothelial Carcinoma (MORPHEUS-UC)


Condition: Urothelial Carcinoma, Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03869190

Sponsor: Hoffmann-La Roche

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

  • for mUC Cohort:
  • Histologically documented, locally advanced or metastatic UC (also termed TCC or urothelial cell carcinoma of the urinary tract; including renal pelvis, ureters, urinary bladder, and urethra)
  • Availability of a representative tumor specimen that is suitable for determination of PD-L1 and/or additional biomarker status by means of central testing
  • Disease progression during or following treatment with no more than one platinum-containing regimen for inoperable, locally advanced or metastatic UC or disease recurrence
  • ECOG Performance Status of 0 or 1
  • Measurable disease (at least one target lesion) according to RECIST v1.1
  • Adequate hematologic and end-organ function
  • Negative HIV test at screening
  • Negative total hepatitis B core antibody (HBcAb) test and hepatitis C virus (HCV) antibody at screening
  • Tumor accessible for biopsy
  • For women of childbearing potential: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating eggs
  • For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm Inclusion Criteria for MIBC Cohorts:
  • ECOG PS of 0 or 1
  • Patients who refuse neoadjuvant cisplatin-based chemotherapy or in whom neoadjuvant cisplatin-based therapy is not appropriate
  • Fit and planned-for cystectomy
  • Histologically documented MIBC (pT2-4, N0, M0), also termed TCC or urothelial cell carcinoma of the urinary bladder
  • N0 or M0 disease by CT or MRI
  • Adequate hematologic and end-organ function
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating eggs as outlined for each specific treatment arm
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as outlined for each specific treatment arm Exclusion Criteria for mUC Cohort:
  • Prior treatment with a T-cell co-stimulating therapy or a CPI including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
  • Prior treatment with any of the protocol-specified study treatments including treatment with poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor, nectin-4 targeting agents, signal regulatory protein alpha-targeting agents, or TIGIT-targeting agents, Trop-2 targeting agents, FAP-directed therapies, 4-1BB (CD137)-directed therapies, or topoisomerase 1 inhibitors
  • Treatment with investigational therapy within 28 days prior to initiation of study treatment
  • Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment
  • Eligibility only for the control arm
  • Prior allogeneic stem cell or solid organ transplantation
  • Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to the initiation of study treatment
  • Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment or anticipation of need for systemic immunosuppressant medication during study treatment
  • Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the last dose of atezolizumab
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
  • Uncontrolled tumor-related pain
  • Uncontrolled or symptomatic hypercalcemia
  • Symptomatic, untreated, or actively progressing CNS metastases
  • History of leptomeningeal disease
  • Active or history of autoimmune disease or immune deficiency
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis
  • History of malignancy other than UC within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
  • Active tuberculosis
  • Severe infection within 4 weeks prior to initiation of study treatment
  • Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
  • Significant cardiovascular disease
  • Uncontrolled hypertension
  • Grade 3 or greater hemorrhage or bleeding event within 28 days prior to initiation of study treatment
  • Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment
  • Pregnancy or breastfeeding, or intention of becoming pregnant during the study
  • Additional drug-specific exclusion criteria might apply Exclusion for MIBC Cohorts:
  • Patients will be excluded from the Atezo + Tira arm within the MIBC Cohorts if they meet any of the additional criteria for that arm.
  • Prior treatment with systemic immunostimulatory agents prior to the initiation of study treatment
  • Eligibility only for the control arm
  • Prior allogeneic stem cell or solid organ transplantation
  • Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressant medication during study treatment, with the following exceptions: Patients who received acute, low-dose, systemic immunosuppressant medications, or a one-time pulse dose of systemic immunosuppressant medication are eligible for the study after Medical Monitor approval has been obtained. Patients who received mineralocorticoids, corticosteroids for chronic obstructive pulmonary disease or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.
  • Severe infection within 4 weeks prior to initiation of study treatment
  • Pregnancy or breastfeeding, or intention of becoming pregnant during the study Additional Exclusion Criteria for Atezo+Tira in the MIBC Cohorts:
  • Active Epstein-Barr virus (EBV) infection or known or suspected chronic active EBV infection at screening Additional

Exclusion Criteria:

  • for mUC Cohort:
  • Prior treatment with a T-cell co-stimulating therapy or a CPI including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
  • Prior treatment with any of the protocol-specified study treatments including treatment with poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor, nectin-4 targeting agents, signal regulatory protein alpha-targeting agents, or TIGIT-targeting agents, Trop-2 targeting agents, FAP-directed therapies, 4-1BB (CD137)-directed therapies, or topoisomerase 1 inhibitors
  • Treatment with investigational therapy within 28 days prior to initiation of study treatment
  • Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment
  • Eligibility only for the control arm
  • Prior allogeneic stem cell or solid organ transplantation
  • Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to the initiation of study treatment
  • Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment or anticipation of need for systemic immunosuppressant medication during study treatment
  • Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the last dose of atezolizumab
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
  • Uncontrolled tumor-related pain
  • Uncontrolled or symptomatic hypercalcemia
  • Symptomatic, untreated, or actively progressing CNS metastases
  • History of leptomeningeal disease
  • Active or history of autoimmune disease or immune deficiency
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis
  • History of malignancy other than UC within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
  • Active tuberculosis
  • Severe infection within 4 weeks prior to initiation of study treatment
  • Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
  • Significant cardiovascular disease
  • Uncontrolled hypertension
  • Grade 3 or greater hemorrhage or bleeding event within 28 days prior to initiation of study treatment
  • Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment
  • Pregnancy or breastfeeding, or intention of becoming pregnant during the study
  • Additional drug-specific exclusion criteria might apply Exclusion for MIBC Cohorts:
  • Patients will be excluded from the Atezo + Tira arm within the MIBC Cohorts if they meet any of the additional criteria for that arm.
  • Prior treatment with systemic immunostimulatory agents prior to the initiation of study treatment
  • Eligibility only for the control arm
  • Prior allogeneic stem cell or solid organ transplantation
  • Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressant medication during study treatment, with the following exceptions: Patients who received acute, low-dose, systemic immunosuppressant medications, or a one-time pulse dose of systemic immunosuppressant medication are eligible for the study after Medical Monitor approval has been obtained. Patients who received mineralocorticoids, corticosteroids for chronic obstructive pulmonary disease or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.
  • Severe infection within 4 weeks prior to initiation of study treatment
  • Pregnancy or breastfeeding, or intention of becoming pregnant during the study Additional Exclusion Criteria for Atezo+Tira in the MIBC Cohorts:
  • Active Epstein-Barr virus (EBV) infection or known or suspected chronic active EBV infection at screening Additional Exclusion Criteria for Atezo+RO7122290 Arm in the MIBC Cohorts:
  • Clinically significant cardiovascular or cerebrovascular disease within 6 months prior to Day 1 of study drug administration will be excluded.

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An Open-label, Dose-escalation, Bi-weekly Phase I+II Clinical Trial in Treating Patients With Locally Advanced and Metastatic Urothelial Carcinoma


Condition: Urothelial Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03676946

Sponsor: Lee's Pharmaceutical Limited

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

  1. The subject voluntarily gives written informed consent to participate in the study.
  2. Female and male patients aged between 18 and 75 (inclusive).
  3. Subjects must have a histologically and/or cytologically confirmed diagnosis of urothelial carcinoma and the recurrence or metastasis is confirmed again after recurrence, and must have failed or are intolerable to standard therapies or for whom no standard therapies exist.
  4. Must have measurable disease with at least 1 unidimensional measurable lesion (recorded as the maximum diameter) based on RECIST 1.
  5. Eastern Cooperative Oncology Group(ECOG) performance status of 0 or 1, with estimated life expectancy of at least 3 months.
  6. Adequate blood routine, hepatic and renal function: 1)neutrophil count (ANC) absolutely acuity≥1.5 x 109 / L; 2)platelet count≥80 x 109 / L ; 3)hemoglobin≥90 g/L; 4)serum albumin≥28 g/L; 5)bilirubin≤1.5 x ULN (upper limit of normal ); 6)ALT and AST≤1.5 x ULN, such as liver metastasis, ALT (alanine transaminase) and AST≤5 x ULN; 7)serum Cr≤1.25 x ULN or endogenous creatinine clearance≥50 ml/min (according Cockcroft Gault formula). 7.Female patients of reproductive age should take effective contraception during the study period and within 3 months after the study treatment period. The serum or urine human chorionic gonadotropin (HCG) examination must be negative within 7 days before the study was enrolled.

Exclusion Criteria:

  1. Any active autoimmune disease or history of autoimmune disease (such as, but not limited to, interstitial pneumonia, uveitis, enteritis, hepatitis, arthritis, nephritis, pituitary inflammation, hyperthyroidism, hypothyroidism, etc.); Patients with vitiligo or asthma in childhood, and still need medical intervention in adult; Patients need bronchodilators for medical intervention of asthma.
  2. Patients are using immunosuppressive agents, or systemic, or absorbable topical corticosteroid medications to achieve immunosuppressive purposes (doses >10mg/day prednisone or equivalent), which is ongoing 2 weeks before enrollment.
  3. Have received any form of organ transplantation, including allogeneic stem cell transplantation.
  4. Known allergy to macromolecular protein inhibitors or any of the components of ZKAB0
  5. Suffering from other malignant tumors other than this diseases in 5 years except skin basal cell and squamous cell carcinoma or cervical carcinoma in situ.
  6. Central nervous system metastases with clinical symptoms (such as cerebral edema and brain metastases requiring corticosteroid intervention). Previous treatment with brain or meningeal metastasis, such as clinical stabilization (MRI) less than 2 months, or systemic corticosteroid (dose >10mg/day prednisone or equivalent) less than 2 weeks.
  7. Patients with clinical symptoms or heart diseases that cannot be well controlled, such as heart failure above New York Heart Association (NYHA) 2 grade, unstable angina pectoris, myocardial infarction in 1 year, and clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention, left ventricular ejection fraction < 50% at rest as shown in the ultrasound cardiogram.
  8. Patients who had received radiotherapy, chemotherapy, surgery or molecular targeted therapy before, were given less than 4 weeks or 5 half-life (longer time) after the treatment (if treated with nitrosourea or mitomycin previously, the time interval between the end of chemotherapy and study inclusion was less than 6 weeks); Adverse events caused by previous treatment did not recover to level 1 of CTCAE, except for hair loss.
  9. Active infection, or unexplained fever> 38.5 degrees during screening period or before the first dose of ZKAB001 (subjects with fever from the tumor could be enrolled upon investigator's decision).
  10. Human immunodeficiency virus (HIV) positive, syphilis spirochete positive, untreated active hepatitis.
  11. The patient is participating in other clinical studies or is less than 1 month away from the end of the previous clinical study.
  12. Patients may need to receive other systemic cancer treatment during study period.
  13. Prior therapy with an anti-PD 1, anti-PD L1, or anti-CTLA-4 (Cytotoxic T Lymphocyte Antigen-4) antibody (or any other agents that target immunoregulatory receptor).
  14. Recent history of prophylactic non-cancer vaccination (such as seasonal influenza vaccine and human papillomavirus (HPV) vaccine) within 28 days before screening.
  15. History of mental drug abuse, alcohol abuse or drug abuse.
  16. Pregnant or lactating women.
  17. Any mental condition that prevents the understanding or provision of an informed consent.
  18. It is determined by the investigator that the patient has other factors that may lead to the termination of the study, such as other serious diseases or serious laboratory test abnormalities or other factors that may affect the safety of the subjects, family or social factors that may affect the study data and sample collection.

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A Phase 3, Randomized, Double-blind Trial of Nivolumab in Combination With Intravesical BCG Versus Standard of Care BCG Alone in Participants With High-risk Non-muscle Invasive Bladder Cancer That Is Persistent or Recurrent After Treatment With BCG


Condition: Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04149574

Sponsor: Bristol-Myers Squibb

Phase: Phase 3

Eligibility:

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

Exclusion Criteria:

  • Previous or concurrent muscle invasive, locally advanced, or disseminated/metastatic UC
  • UC in the upper genitourinary tract (kidneys, renal collecting systems, ureters) within 24 months of enrollment
  • UC and/or CIS in the prostatic urethra within 12 months of enrollment
  • Prior surgery (other than transurethral resection of the bladder tumor (TURBT)/biopsies) for bladder cancer; prior radiation therapy, or systemic chemotherapy or immunotherapy for bladder cancer or UC Other inclusion/exclusion criteria apply.

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Intravesical Instillation Therapy With Bacillus Calmette-Guérin (BCG) and Sequential BCG and Electromotive Mitomycin-C (EMDA-MCC) in Patients With High-risk Non-muscle-invasive Bladder Carcinoma


Condition: Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03664869

Sponsor: Turku University Hospital

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  • Histologically proven non-muscle-invasive tumour types confined to the urinary bladder
  • Carcinoma in situ with or without a papillary tumour(s)
  • Ta tumour(s) of high-grade
  • Any T1 tumour(s)
  • Written informed consent is required from every eligible patient
  • Second resection performed in case of T1 tumour
  • Adequate physical and mental condition to participate in the study (as judged by treating physician

Exclusion Criteria:

  • Ta low grade tumour(s)
  • Muscle invasive (pT≥2) tumors
  • Urothelial cancer involving the prostatic urethra or upper urinary tract
  • Non-urothelial bladder cancer.
  • Prior BCG failure (If the patient has previously been successfully treated with BCG, and duration from the last instillation is >12 months, participation may be considered, if bladder preserving is chosen)
  • Prior or concurrent immunotherapy
  • Any medication or condition considered as contraindication to BCG or MMC (as judged by the treating physician)
  • Urethral stricture, stone disease, chronic urinary tract infection or any other urological condition that may comprise study participation (as judged by the treating physician)
  • Known allergy to MMC or BCG
  • Age < 18 years
  • Pregnancy or lactating patient
  • Other untreated or unstable malignancy in risk of recurrence/progression (as judged by the treating physician)
  • Cardiac pacemaker
  • Expected survival time less than one year
  • Expected poor compliance

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A Clinical, Non-intervention Study of the Cxbladder Urine Test for the Detection of Recurrent Urinary Tract Urothelial Carcinoma


Condition: Bladder Cancer

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT03673202

Sponsor: London Health Sciences Centre

Phase:

Eligibility:

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

Inclusion Criteria:

  1. Patient is undergoing investigative cystoscopies for the monitoring of recurrence of urinary tract UC at intervals prescribed by the clinical practitioner
  2. Patients on an "all-comers" basis
  3. Positive diagnosis for primary or recurrent bladder tumour within the past 5 years
  4. Able provide a voided urine sample of the required minimum volume
  5. Able to give written consent
  6. Able and willing to comply with study requirements
  7. Aged 18 years or older

Exclusion Criteria:

  1. Prior genitourinary manipulation (flexible or rigid cystoscopy / catheterisation, urethral dilation) in the 14 days before urine collection,
  2. Patients who had exposure to intravesical BCG, had completed induction BCG but without a subsequent clear cystoscopy
  3. Recent history of glomerulonephritis, nephrosis or other renal inflammatory disorders,
  4. Recent history of pyelonephritis
  5. Total cystectomy of the bladder, neo bladders and illeal conduits
  6. Previous muscle invasive bladder tumour (pT2 or greater)

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Randomized Phase 2 Trial of Gemcitabine + Carboplatin + Nivolumab Versus Gemcitabine + Oxaliplatin + Nivolumab in Cisplatin-ineligible Patients With Metastatic Urothelial Cancer


Condition: Metastatic Urothelial Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03451331

Sponsor: Matthew Galsky

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Subject must meet all the following applicable inclusion criteria to participate in this study:
  • Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
  • Age ≥ 18 years at the time of consent.
  • Eastern Cooperative Oncology Group (ECOG) performance status of = 2
  • Able to comply with the study protocol, in the investigator's judgment.
  • Histologically documented, locally advanced (T4b, any N; or any T, N 2-3) or metastatic urothelial carcinoma (mUC) (M1, Stage IV) (also termed TCC or UCC of the urinary tract; including renal pelvis, ureters, urinary bladder, and urethra) Patients with mixed histologies are required to have a dominant transitional cell pattern. Locally advanced bladder cancer must be inoperable on the basis of involvement of pelvic sidewall or adjacent viscera (clinical Stage T4b) or bulky nodal metastasis (N2-N3).
  • Measurable disease, as defined by RECIST v1.1
  • Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens (metastatic specimens preferable but if not available primary tumor specimens that are at least muscle-invasive are acceptable) in paraffin blocks (blocks preferred) or at least 15 unstained slides. Subjects without adequate archival tumor tissue or for whom a biopsy is not considered possible may be considered for enrollment on a case by case basis after discussion with the sponsor-investigator.
  • No prior chemotherapy for inoperable locally advanced or mUC. For patients who received prior adjuvant/neoadjuvant chemotherapy or chemo-radiation for urothelial carcinoma, a treatment-free interval > 12 months between the last treatment administration and the date of recurrence is required in order to be considered treatment naive in the metastatic setting.
  • Cisplatin-ineligible as defined by at least one of the following:
  • Calculated creatinine clearance ≥ 30 (Cockroft-Gault)
  • ECOG performance status of 2 or greater
  • CTCAE v4 Grade ≥ 2 audiometric hearing loss
  • Demonstrate adequate organ function. All screening labs to be obtained within 28 days prior to registration:
  • Hematological:
  • Absolute Neutrophil Count (ANC) ≥ 1.5 x 10^9/L
  • Hemoglobin (Hgb) ≥ 9 g/dL
  • Platelets ≥ 100 x 10^9/L
  • Renal: • Calculated creatinine clearance ≥ 30 mL/min (Cockroft-Gault)
  • Hepatic:
  • Bilirubin ≤ 1.5 × upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
  • Aspartate aminotransferase (AST) ≤ 3 × ULN
  • Alanine aminotransferase (ALT) ≤ 3 × ULN
  • Women of childbearing potential must have a negative serum or urine pregnancy.
  • Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception as stated for the timeline below. Male subjects are not required to use contraception. NOTE: Women of childbearing potential is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 62 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL. NOTE: Women of childbearing potential (WOCBP) receiving nivolumab will be instructed to adhere to contraception for a period of 5 months after the last dose of investigational product.

Exclusion Criteria:

  • Subjects meeting any of the criteria below may not participate in the study:
  • Active infection requiring systemic therapy.
  • Pregnant or breastfeeding
  • Any serious or uncontrolled medical disorder that, in the opinion of the site investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
  • Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured.
  • 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.
  • Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of 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.
  • Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
  • Grade ≥ 2 neuropathy (NCI CTCAE version 4).
  • Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (RNA) or hepatitis C antibody (HCV antibody) indicating acute or chronic infection.
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  • Evidence of interstitial lung disease or active, non-infectious pneumonitis.
  • Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class III or greater), myocardial infarction within 3 months prior to randomization, unstable arrhythmias, or unstable angina.
  • Known left ventricular ejection fraction (LVEF) < 40% Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or LVEF 40%-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.
  • Solid organ or tissue transplant including stem cell transplant

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Phase II Trial of Intravesical Gemcitabine and MK-3475 (Pembrolizumab) in the Treatment of Patients With BCG-Unresponsive Non-Muscle Invasive Bladder Cancer


Condition: Bladder Urothelial Carcinoma In Situ, Infiltrating Bladder Mixed Carcinoma, Stage 0a Bladder Cancer AJCC v8, Stage 0is Bladder Cancer AJCC v8, Stage I Bladder Cancer AJCC v8

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04164082

Sponsor: National Cancer Institute (NCI)

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • High grade Ta, T1 or CIS urothelial carcinoma. Accrual of patients with Ta or T1 disease may be closed to ensure adequate patients enrollment to meet the primary endpoint
  • Persistent disease after completing therapy with at least induction BCG (>= 5 doses) and the first round of maintenance or second induction course (>= 2 doses)
  • Persistent high risk NMIBC (T1, high grade Ta and/or CIS) must be within 9 months of the last BCG instillation despite having received adequate BCG as defined above
  • High grade T1 after completing therapy with at least induction BCG (>= 5 doses) or after completing therapy with at least induction BCG (>=5 doses) and first round of maintenance or second induction course (>= 2 doses)
  • Persistent high risk NMIBC (T1, high grade Ta and/or CIS) must be within 9 months of the last BCG instillation despite having received adequate BCG as defined above
  • Mixed variant histology (adenocarcinoma, squamous cell carcinoma) is eligible, but pure variant histology is ineligible
  • Patients who are disease free at 6 months after starting BCG but have high grade recurrence (T1, Ta, CIS) while on maintenance therapy would be eligible
  • The recurrence must be within 6 months of the last BCG dose
  • Patients must be deemed unfit for radical cystectomy by the treating physician or refuse radical cystectomy
  • All visible tumor must be completely resected 60 days prior to registration (residual pure CIS is permitted)
  • All patients must have histologically confirmed urothelial cancer of the bladder within 60 days prior to registration. All patients must have had a cystoscopy without papillary tumor and negative urinary cytology within 21 days of registration. (positive cytology is allowed in patients with pure CIS)
  • All patients with T1 tumors must undergo a re-staging transurethral resection of bladder tumor (TURBT) within 60 days of registration. There must be uninvolved muscularis propria present in the re-staging TURBT. The initial TURBT prior to re-staging TURBT may be greater than 60 days prior to registration
  • Patients must have had imaging with computed tomography (CT) or magnetic resonance imaging (MRI) abdomen/pelvis within 90 days of registration demonstrating no evidence of metastasis.
  • Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects
  • Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study due to the teratogenic potential of the therapy utilized in this trial. Include as applicable: Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives or double barrier method (diaphragm plus condom)
  • A woman of childbearing potential (WOCBP) must not have a positive urine pregnancy test within 7 days prior to registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Patients must not be pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with registration through the last dose of treatment
  • Age >= 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Absolute neutrophil count (ANC) >= 1,500/mm^3
  • Platelet count >= 100,000/mm^3
  • Hemoglobin >= 9.0 g/dL
  • Creatinine =< 1.5 x upper limit of normal (ULN)
  • In patients with creatinine > 1.5 x ULN, if measured or calculated creatinine clearance > 30 mL/min, then patient is eligible
  • Total bilirubin =< 1.5 x ULN
  • In patients with a total bilirubin > 1.5 x ULN, if direct bilirubin < 1.0 X ULN, then patient is eligible
  • Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) =< 2.5 x ULN
  • Patients with human immunodeficiency virus (HIV) are eligible with the following:
  • On effective anti-retroviral therapy with undetectable viral load within 6 months of registration

Exclusion Criteria:

  • Patients cannot have had a history of urothelial carcinoma in the ureters or prostatic urethra 24 months prior to registration
  • Patients must not be currently participating in or have participated in a study of an investigational agent or have used an investigational device within 4 weeks prior to study registration
  • Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been more than 4 weeks after the last dose of the previous investigational agent at time of registration
  • Patients must not have prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137)
  • Patients must not have undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years prior to registration. (Participants who have had a transplant greater than 5 years ago are eligible as long as there are no symptoms of graft versus host disease [GVHD])
  • Patients must not have received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to treatment
  • Note: Participants must have recovered from all adverse events (AEs) due to previous therapies to =< grade 1 or baseline. Participants with =< grade 2 neuropathy may be eligible
  • Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment
  • Patients must not have received prior radiotherapy within 2 weeks of study registration. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis
  • Patients must not have received radiation therapy to the lung that is > 30 Gy within 6 months prior to trial registration
  • Patients must not have had an active autoimmune disease requiring systemic treatment within 7 days prior to registration. Autoimmune diseases include, but not limited to, lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis
  • Patients must not have 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 prior to registration
  • Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
  • Patients must not have a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
  • Patients must not have active tuberculosis
  • Patients must not have been treated with antibiotics for an active infection within 14 days prior to registration. Prophylactic antibiotics are permitted. Treatment for a urinary tract infection (UTI) is allowed but must be deemed adequately treated by the treating physician prior the start of cycle 1 (C1) day 1 (D1)
  • Patients must not have a history of idiopathic pulmonary fibrosis or organizing pneumonia
  • Patients must not have a history of (non-infectious) pneumonitis that required steroids or have current pneumonitis
  • HIV-infected participants must not have a history of Kaposi sarcoma and/or multicentric Castleman disease
  • Patients must not have a known additional malignancy that has had progression or has required active treatment in the last three years. Exceptions include basal or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. A history of prostate cancer that was treated with definitive intent is allowed, provided that the prostate-specific antigen (PSA) is undetectable for at least 1 year while off androgen deprivation therapy
  • Patients must not have known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment
  • Patients must not have severe hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients
  • Patients must not have an active infection requiring systemic therapy
  • Patients must not have a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected) infection
  • Note: No testing for hepatitis B and hepatitis C is required unless mandated by a local health authority
  • Patients must not have received live vaccines within 30 days of study drug administration. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed
  • Physicians should consider whether any of the following may render the patient inappropriate for this protocol:
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator

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Evaluation of UroX™ Biomarker Screening Test in the Investigation of Bladder Cancer From Urine Samples - a Single Site Pilot Study


Condition: Bladder Cancer

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT03973307

Sponsor: East and North Hertfordshire NHS Trust

Phase:

Eligibility:

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

Inclusion Criteria:

  • Patients aged ≥ 18 years of age
  • Patients under investigation for bladder cancer due to undergo investigative standard of care biopsy

Exclusion Criteria:

  • Patients aged < 18 years of age
  • Patients who are currently undergoing radiation therapy.
  • Proposed subject has no bladder (due to surgical removal).
  • No cystoscopy and/or pathology information for proposed subject (following cystoscopy for final inclusion in study results)
  • Patients unable or unwilling to provide consent
  • Patients currently on investigational drug trials
  • Patients with Catheter in Situ

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Phase II Study of Oral Metformin for Intravesical Treatment of Non-muscle-invasive Bladder Cancer


Condition: Superficial Bladder Cancer, Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03379909

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

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Age > 18 years.
  • Patients with primary or recurrent multiple histologically confirmed Ta or T1 (non-muscle invasive), G1 or G2 (low grade) urothelial carcinoma of the bladder with no evidence of carcinoma in situ.
  • Patients must have at least 2 lesions but no more than 10.
  • The resected lesions must contain detrusor muscle to confirm a Ta/T1 disease.
  • All visible lesions must be completely removed by transurethral resection at entry to the study, except for an untouched marker lesion measuring 0.5-1.0 cm in its greatest dimension.
  • Bimanual examination immediately following transurethral resection under anaesthesia should be carried out and no mass should be felt.
  • Adequate renal function (creatinine <150 μmol/L and/or an eGFR >60 ml/L).
  • Adequate liver function (bilirubin <1.5 times upper limit of normal, ALAT or ASAT <2.5 the upper limit of normal).
  • Eligible patients must be fully informed of the investigational nature of the study and written signed informed consent must be obtained prior to any study specific investigations.
  • Mentally, physically, and geographically able to undergo treatment and follow up.

Exclusion Criteria:

  • Patients having muscle-invasive disease (stage T2 or greater) or CIS.
  • Patients with grade 3 (high-grade) tumours.
  • Patients with diabetes mellitus receiving metformin or having received metformin in the past 6 months.
  • Patients who have received intravesical treatment (chemotherapy or immunotherapy) within the last 3 months.
  • Patients that are currently receiving other anti-cancer therapy.
  • Patients with existing urinary tract infection or recurrent severe bacterial cystitis.
  • Patients that need to be treated with a transurethral catheter.
  • Patients with urogenital tumours with histology other than urothelial carcinoma (i.e. squamous cell or adenocarcinoma) or with urothelial carcinoma involving the upper tract or the prostatic urethra.
  • Patients with a history of other primary malignancy (other than squamous or basal cell skin cancers or cone biopsied CIS of the uterine cervix or prostate carcinoma treated curatively with normal PSA values at inclusion) in the last five years.
  • Patients with active, uncontrolled impairment of the renal, hepatobiliary, cardiovascular, gastrointestinal, urogenital, neurologic or hematopoietic systems that, in the opinion of the investigator, would predispose to the development of complications from the administration of metformin.
  • Patients who are using loop diuretics, cimetidine, ranitidine, cetirizine, trimethoprim, vandetanib, kinidine and/or HIV medication, for which no reasonable alternative is available.
  • Women who are pregnant or lactating. Individuals of reproductive potential may not participate unless agreeing to use an effective contraceptive method for themselves and/or their sexual partner.
  • Patients with ECOG-WHO performance status of 3 or 4.
  • Patients with a known history of alcohol abuse.
  • Patients with a known hypersensitivity to metformin.
  • Patients who in the investigator's opinion, cannot comply with provisions of the protocol or do not understand the nature of the 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.

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Basal Tumours in Bladder Cancer, Response to chemoTherapy


Condition: Bladder Cancer, Chemotherapy Effect

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT04089748

Sponsor: University Hospital, Rouen

Phase:

Eligibility:

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

Inclusion Criteria:

  • of Patients enrolled in VESPER study: Tumors from patient having muscle invasive bladder cancer who benefit from neoadjuvant chemotherapy with cisplatine included in VESPER cohort and :
  • having signed an informed consent form for the participation to the collection or
  • dead/lost to follow-up without prior opposition expressed against research program,
  • genetic analysis will only be carried out for patients who have signed the genetic consent form. Inclusion Criteria of Patients from St Louis cohort not enrolled in VESPER study: Tumors from patient having muscle invasive bladder cancer who benefit from neoadjuvant chemotherapy with cisplatine included in Saint-Louis cohort and :
  • having received an informed form for the participation to the collection and not having expressed opposition against research program within 1 month or
  • dead/lost to follow-up without prior opposition expressed against research program,

Exclusion Criteria:

  1. -Patients enrolled in VESPER study:Tumors from patient having withdrawn his/her informed consent form for the participation to the collection and/or VESPER project. OR -Patients from St Louis not enrolled in VESPER study:Tumors from patient having expressed opposition against research program after 1 month for the participation to the collection.

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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

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