Locally advanced or metastatic Transitional Cell Carcinoma (TCC) of the urothelium MedDRA version: 8.1 Level: LLT Classification code 10044412 Term: Transitional cell carcinoma
Conditions
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Provided signed written informed consent Target population 2) Histologic diagnosis of predominantly locally advanced or metastatic transitional cell carcinoma (TCC) of the urothelium (urinary bladder, kidney, renal pelvis, or ureter); 3) Ineligibility for cisplatin-based therapy because of at least one of the following two medical conditions: - Calculated creatinine clearance (Cockroft-Gault formula, see Appendix 3) = 60 mL/min; or, - New York Heart Association Classification Stage III-IV Congestive Heart Failure (see Protocol Appendix 4); 4) Measurable disease documented by imaging with at least one uni-dimensional lesion; 5) ECOG performance status of 0, 1, or 2 (see Protocol Appendix 5); 6) The following laboratory parameters: - Absolute Neutrophil Count = 1,500 mm3, - Platelet count = 100,000 mm3, - Serum total bilirubin = 1.5 x upper limit of normal (ULN), - Transaminases = 2.5 x ULN [> 5 times ULN only in case of liver metastasis]. 7) If patient received neoadjuvant or adjuvant chemotherapy, he/she must have documented relapse, = 6 months after the last dose of chemotherapy. Age and Sex 8) Men and women = age 18 years of age Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Sex and Reproductive Status 1) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 12 weeks after the study. 2) WOCBP using a prohibited contraceptive method. 3) Women who are pregnant or breastfeeding. 4) Women with a positive pregnancy test on enrollment or prior to study drug administration. 5) Sexually active fertile men not using effective birth control during the study and up to 6 months after the study if their partners are women of child-bearing potential. Target Disease Exceptions 6) Diagnosis of predominantly non-transitional cell carcinoma of the urothelium (adenocarcinoma, squamous cell carcinoma, small cell, or other) or TCC originating at sites other than the urothelium. 7) Patients in whom radiation or surgery is indicated. Medical History and Concurrent Diseases 8) Previous systemic chemotherapy treatment for locally advanced or metastatic disease (intravesical treatment is allowed, as well as neoadjuvant and adjuvant chemotherapy that was completed = 6 months before documented PD). 9) Known brain metastases or leptomeningeal involvement. CT scans are not required unless there is clinical suspicion of central nervous system (CNS) disease. 10) National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (v. 3.0) = Grade 3 peripheral neuropathy. 11) Prior radiation to = 30% of the bone marrow (See Protocol Appendix 6). 12) Other serious illness or medical condition including: - Infection requiring systemic anti-infective therapy, - any medical condition that might be aggravated by treatment or which could not be controlled, for instance patients with unstable angina, patients with myocardial infarction within 6 months and/or poorly controlled hypertension. 13) Other malignancies except adequately treated basal carcinoma of the skin, in-situ prostrate cancer Gleason = 6, in-situ cervix carcinoma or any other tumor with a disease free interval = 5 years. 14) Psychological, familial, or sociological conditions which do not permit medical follow-up and/or compliance with the study protocol. Physical and Laboratory Test Findings 15) Inadequate renal function defined by a serum creatinine clearance = 20 mL/min (Cockcroft-Gault formula, see Protocol Appendix 3). Allergies and Adverse Drug Reactions 16) Prior allergic reaction to any vinca alkaloid. Prohibited Therapies and/or Medications 17) Patients who require treatment with ketoconazole, itraconazole, ritonavir, amprenavir and indinavir. 18) Any concurrent chronic systemic immune therapy (including steroids), chemotherapy, radiation therapy, hormonal therapy (except for physiologic replacement), or any other investigational agent. Other Exclusion Criteria 20) Prisoners or patients who are compulsorily detained
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the progression-free survival (PFS) between the two treatment arms with progression as defined by Response Evaluation Criteria In Solid Tumors (RECIST) in patients randomized to receive vinflunine/gemcitabine to those randomized to receive placebo/gemcitabine, for first-line locally advanced or metastatic patients with TCC of the urothelium who are not eligible to receive cisplatin-based therapy.;Secondary Objective: 1) To compare the response rate [Complete Response (CR) + Partial Response (PR), as defined by RECIST] between the two treatment arms. 2) To compare overall survival (OS) between the two treatment arms. 3) To compare disease control rate [CR + PR + Stable Disease (SD)] between the two treatment arms. 4) To estimate the duration of response in each treatment arm. 5) To estimate time to response in each treatment arm. 6) To evaluate the safety profile of each treatment.;Primary end point(s): To compare the progression-free survival (PFS) between the two treatment arms with progression as defined by Response Evaluation Criteria In Solid Tumors (RECIST) in patients randomized to receive vinflunine/gemcitabine to those randomized to receive placebo/gemcitabine, for first-line locally advanced or metastatic patients with TCC of the urothelium who are not eligible to receive cisplatin-based therapy. | — |
Countries
Belgium, Denmark, France, Greece, Italy, Spain, United Kingdom
Outcome results
None listed