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
Overview
- Phase
- Phase 2
- Intervention
- Vinflunine, Gemcitabine
- Conditions
- Bladder Transitional Cell Carcinoma Stage IV
- Sponsor
- Pierre Fabre Medicament
- Enrollment
- 69
- Locations
- 1
- Primary Endpoint
- Disease control rate as defined by RECIST criteria (version 1.1) as a percentage of best overall responses of Complete (CR) + Partial (PR) + Stable Disease (SD) for both Vinflunine-Gemcitabine and Vinflunine-Carboplatin combinations
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief 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.
Detailed Description
Gemcitabine and carboplatin have been the most studied and used anticancer agents in cisplatin-unfit patients with advanced urothelial carcinoma. Both agents previously demonstrated clinical activity as single agent and/or as part of combination regimen in patients with advanced or metastatic disease even if clinical benefits and survival remains limited in this setting for this population. The purpose of this study is to test in a randomized trial enrolling patients with renal impairment or moderate congestive heart failure two combinations of a novel cytotoxic agent, vinflunine, one with gemcitabine and another with carboplatin in order to determine the most promising combination in the first line treatment of advanced/metastatic urothelial carcinoma.
Investigators
Eligibility 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)
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
Arms & Interventions
Vinflunine plus Gemcitabine
Intervention: Vinflunine, Gemcitabine
Vinflunine plus Carboplatin
Intervention: Vinflunine, Carboplatin
Outcomes
Primary Outcomes
Disease control rate as defined by RECIST criteria (version 1.1) as a percentage of best overall responses of Complete (CR) + Partial (PR) + Stable Disease (SD) for both Vinflunine-Gemcitabine and Vinflunine-Carboplatin combinations
Time Frame: Change from baseline in tumor assessment at 12 weeks (cycle 4)
Assessment of lesions (measurable and non-measurable) should be performed at baseline and every 6 weeks (assessment interval). Evaluable patients: all baseline lesions must have been assessed at least once after the second cycle (6 weeks); patients who progress before the first evaluation will be considered as early progression. Primary analysis is planned on the intent to treat population, secondary analysis being performed on the evaluable population.
Secondary Outcomes
- Tumor Response Rate as defined by RECIST criteria (version 1.1) with a best response as Complete (CR) or Partial (PR)(Change from baseline in tumor assessment at 12 weeks (cycle 4))
- Duration of Disease control in Participants With Best Response of CR + PR + SD(From the date of randomisation until the date of documented progression or date of death due to any cause, assessed up to 10 months)
- Duration of Response in Participants With Best Response of CR or PR(From the date that measurement criteria are first met for complete or partial response until the date of documented progression or date of death due to any cause, assessed up to 10 months)
- Time to First Response calculated among the responders(From the date of randomisation up to the first report of documented response, assessed up to 12 weeks (cycle 4).)
- Time to Treatment Failure(From the date of randomisation until tumor progression, unacceptable toxicity, withdrawal of patient consent, lost to follow-up or start of new anticancer therapy, assessed up to 10 months.)
- Progression Free Survival(From the date of randomisation until the date of progression or the date of death from any cause if no progression was recorded before, median patient follow-up of 11 months)
- Overall Survival(From the time of randomisation up to death or last follow-up, assessed with a median patient follow-up of 15 months (assessed up to 24 months))
- Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) and AEs Leading to Discontinuation(AE and SAE will be collected up to 30 days after the last treatment administration, on an expected average period of 17 weeks)