| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Histologically confirmed diagnosis of locally advanced or metastatic predominantly transitional cell carcinoma of the urothelium (TCCU) [urinary bladder, kidney, renal pelvis, or ureter] |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10044412 |
|
| 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 determine the disease control rate as defined by RECIST assessment criteria [Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) rates] for both Vinflunine-Gemcitabine and Vinflunine-Carboplatin combinations. |
|
| E.2.2 | Secondary objectives of the trial |
| • To assess the safety profile of the treatment. • To evaluate other efficacy parameters: Objective Response Rate (CR + PR rates), duration of response and duration of disease control, Time to treatment failure (TTF), Progression free survival (PFS) and Overall survival (OS). |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| • Man or woman aged >or=18 years and < 80 years • Signed written informed consent • Histologically confirmed diagnosis of locally advanced or metastatic predominantly transitional cell carcinoma of the urothelium (TCCU) [urinary bladder, kidney, renal pelvis, or ureter] • With the following disease conditions : - Ineligibility for cisplatin-based therapy because of at least one of the following two medical conditions: Calculated creatinine clearance (Cockroft-Gault formula) < 60 mL/min New York Heart Association Classification Stage II-III Congestive Heart Failure (documented by medical history) • “Measurable” disease with at least one uni-dimensional lesion according to RECIST guideline (version 1.1) • ECOG performance status of 0 or 1 • Estimated life expectancy of at least 12 weeks • Patient without prior systemic anticancer therapy unless if it had been administered as neoadjuvant or adjuvant CT for TCCU and if the patient has documented relapse >or=6 months after the last dose of CT (prior intravesical CT allowed) • Adequate bone marrow and hepatic functions as evidenced by: - Absolute Neutrophil Count ≥ 2,000/mm3 (>or= 2.0 x 109/L); - Haemoglobin >or= 10 g/dL; - Platelet count >or=100,000/mm3; - Serum total bilirubin <or= 1.5 x upper limit of normal (ULN); - Transaminases < or = 2.5 x ULN [<or = 5 x ULN only in case of liver metastasis]; • Absence of psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; • Patient access to social insurance if applicable in the local regulations • Women of childbearing potential must be using a medically accepted method of contraception to avoid pregnancy during the 2 months preceding the start of study treatment, throughout the study period and for up to 3 months after the last dose of study treatment; women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the start of study treatment • Fertile men must be using an effective method of birth control during the study and up to 6 months after the last dose of study treatment if their partners are women of childbearing potential |
|
| E.4 | Principal exclusion criteria |
| • ECOG performance status >or= 2 • Woman if pregnant or lactating or with positive pregnancy test at inclusion; woman of child-bearing potential who did not use or is unwilling or unable to use an acceptable method to avoid pregnancy during the 2 months preceding the start of study treatment, for the entire study period and for up to 3 months after the last dose of study treatment; sexually active fertile man not using effective birth control during the study and up to 6 months after the last dose of study treatment if his partner is a woman of child-bearing potential • Known brain metastasis or leptomeningeal involvement. (Computed Tomography (CT)-scans are not required to rule this out unless there is clinical suspicion of central nervous system (CNS) disease) • Peripheral neuropathy Grade ≥ 2 by NCI CTC [National Cancer Institute Common Terminology Criteria] • Prior radiation to >or= 30% of the bone marrow or completed < 30 days ago or without full recovery of toxicities • Other serious illness or medical condition including: - Infection requiring systemic anti-infective therapy - Any medical condition that might not be controlled, for instance patients with unstable angina, patients with myocardial infarction within 6 months or uncontrolled diabetes • Prior systemic chemotherapy for advanced or metastatic disease or neoadjuvant/adjuvant chemotherapy that was completed < 6 months before documented progression • Patient who had received any other investigational drug or anti-cancer therapy within 30 days before randomisation • Other malignancies except adequately treated basal carcinoma of the skin, in-situ cervix carcinoma or any other tumor with a disease free interval >or=5 years • Inadequate renal function defined by a serum creatinine clearance < 30 mL/min (Cockcroft-Gault formula) • Known hypersensitivity to the study drugs or to drugs with similar chemical structures • Patients who require treatment with ketoconazole, itraconazole, ritonavir, amprenavir, indinavir, rifampicine (any potent CYP3A4 inhibitor or inducer) or phenytoine • Any concurrent chronic system immune therapy or previous organ allograft • Electrocardiogram (ECG) with significant modifications suggesting a high risk of occurrence of an acute clinical event (such as signs of angina pectoris or high risk arrhythmia…) |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary end point is to determine the disease control rate as defined by RECIST assessment criteria for both Vinflunine-Gemcitabine and Vinflunine-Carboplatin combinations |
|
| 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 | Yes |
| 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 | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| 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 | No |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 27 |
| 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 |
|
| E.8.7 | Trial has a data monitoring committee | No |
| 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
|
| 30 giorni dopo l`ultima somministrazione di farmaco ricevuta dall`ultimo paziente in trattamento. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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