E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced or metastatic Transitional Cell Carcinoma TCC of the urothelium |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061272 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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 |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal 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 |
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E.4 | Principal 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 19 Prisoners or patients who are compulsorily detained |
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E.5 End points |
E.5.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |