E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
It concerns patients who cannot receive a cisplatin-based regimen as first line chemotherapy for an advanced or metastatic Transitional Cell Carcinoma of the Urothelium (TCCU), in particular those having a creatinine clearance < 60 mL/min. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10046722 |
E.1.2 | Term | <Manually entered code. Term in E.1.1> |
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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 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 |
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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).
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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 (≥ 2.0 x 10^9/L) -Haemoglobin ≥ 10 g/dL -Platelet count ≥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; these conditions should be assessed with the patient before registration in the trial •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
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E.4 | Principal exclusion criteria |
•ECOG performance status ≥ 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 ≥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 ≥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…)
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is 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 |
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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 | 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 | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | No |
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 | Yes |
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 | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
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 | 8 |
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 |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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The end of the study is defined as the time from 30 days after the last treatment administration of the last patient under treatment in the study. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |