Brief Title
JAVLOR Association Study in CDDP-unfit Patients With Advanced Transitional Cell Carcinoma: Gemcitabine Versus Carboplatin
Official Title
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
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
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
Secondary Outcome
Tumor Response Rate as defined by RECIST criteria (version 1.1) with a best response as Complete (CR) or Partial (PR)
Condition
Bladder Transitional Cell Carcinoma Stage IV
Intervention
Vinflunine, Gemcitabine
Study Arms / Comparison Groups
Vinflunine plus Gemcitabine
Description:
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
69
Start Date
February 2011
Completion Date
April 2014
Primary Completion Date
October 2013
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)
- 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
Gender
All
Ages
18 Years - 79 Years
Accepts Healthy Volunteers
No
Contacts
Maria De Santis, MD, ,
Location Countries
France
Location Countries
France
Administrative Informations
NCT ID
NCT01599013
Organization ID
L00070 IN 213 P1
Responsible Party
Sponsor
Study Sponsor
Pierre Fabre Medicament
Study Sponsor
Maria De Santis, MD, Principal Investigator, Center for Oncology and Hematology Kaiser Franz Josef Hospital - Vienna - Austria
Verification Date
December 2015