JAVLOR Association Study in CDDP-unfit Patients With Advanced Transitional Cell Carcinoma: Gemcitabine Versus Carboplatin

• Status: Completed
• Trial end date: 2014-04-01
• Target enrollment: 0
• Participant gender: All

Summary

This study is assessing the combination of well known cytotoxics with a novel anti-cancer agent that could be administered as monotherapy without renal toxicity in patients with renal impairment presenting with advanced or metastatic urothelial carcinoma previously treated with a platinum-based regimen. The intent of this study is to clarify the benefit/risk ratio of the two most promising associations of cytotoxics including the novel therapeutic agent, vinflunine: vinflunine-gemcitabine and vinflunine-carboplatin.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Pierre Fabre Medicament
• Treatments: Carboplatin; Cisplatin; Gemcitabine; Vinblastine

Criteria

Inclusion Criteria:

• Man or woman aged ≥ 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)

• Ineligibility for cisplatin-based therapy because of at least one of the following two medical conditions:

• Calculated creatinine clearance (Cockcroft-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 chemotherapy (CT) for TCCU and if the patient has documented relapse ≥ 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 109/L)

• Haemoglobin ≥ 10 g/dL

• Platelet count ≥ 100,000/mm3

• Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN)

• Transaminases ≤ 2.5 x ULN [≤ 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

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.

• Peripheral neuropathy Grade ≥ 2 by NCI CTC

• 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, localised prostate cancer with limited risk of recurrence (pT ≤ 2b, Gleason score ≤ 7) that was incidentally discovered and did not lead to any other treatment apart from prostatectomy, 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, rifampicin (any potent CYP3A4 inhibitor or inducer) or phenytoin

• 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