Randomized phase II study assessing the combination of Vinflunine with Gemcitabine and Vinflunine with Carboplatin in patients ineligible to cisplatin with advanced or metastatic transitional cell carcinoma of the urothelium

Phase 2

Withdrawn

Conditions: 10004994
bladder cancer

Registration Number: NL-OMON36397

Lead Sponsor: Pierre Fabre

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Withdrawn

Sex: Not specified

Target Recruitment: 5

Inclusion Criteria

- Man or woman aged > or equal to 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 equal to 6 months after the last dose of CT (prior intravesical CT allowed)
- Adequate bone marrow and hepatic functions as evidenced by:
+ Absolute Neutrophil Count > or equal to 2,000/mm3 (> or equal to 2.0 x 109/L)
+ Haemoglobin > or equal to 10 g/dL
+ Platelet count > or equal to 100,000/mm3
+ Serum total bilirubin > or equal to 1.5 x upper limit of normal (ULN)
+ Transaminases < or equal to 2.5 x ULN [< or equal to 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

Exclusion Criteria

- ECOG performance status > or equal to 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 childbearing 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 > or equal to 2 by NCI CTC [National Cancer Institute Common Terminology Criteria]
- Prior radiation to > or equal 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 > or equal to 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*)

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Efficacy Measures:<br /><br>- Will be determined by using RECIST criteria (version 1.1). as follows:<br /><br>assessment of lesions (measurable and non-measurable) at baseline and every 2<br /><br>cycles.<br /><br>- Progression and tumor response will be evaluated for all randomized patients<br /><br>by the investigators.<br /><br>- Duration of disease control and response will be evaluated for all patients<br /><br>with disease control and responding patients, respectively.<br /><br>- Moreover, clinical parameters as pain intensity will be performed every 2<br /><br>cycles.<br /><br><br /><br>· Safety Measures: physical examination and vital signs, performance status,<br /><br>complete blood counts, serum biochemistry, clinical safety, adverse events<br /><br>using the NCI Common Toxicity Criteria (version 2.0).</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>To assess the safety profile of the treatment.<br /><br>To evaluate other efficacy parameters: Objective Response Rate (CR + PR rates),<br /><br>duration of response and duration of disease control, Time to treatment failure<br /><br>(TTF), Progression free survival (PFS) and Overall survival (OS).</p><br>

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