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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
18 Years
79 Years
Open (Enrolling)
Bladder Transitional Cell Carcinoma Stage IV

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Trial Information

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

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

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

- 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

- 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

- Patients who require treatment with ketoconazole, itraconazole, ritonavir,
amprenavir, indinavir, rifampicin (any potent CYP3A4 inhibitor or inducer) or

- 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Description:

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.

Outcome Time Frame:

Change from baseline in tumor assessment at 12 weeks (cycle 4)

Safety Issue:


Principal Investigator

Maria De Santis, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Center for Oncology and Hematology Kaiser Franz Josef Hospital - Vienna - Austria


France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Study ID:

L00070 IN 213 P1



Start Date:

February 2011

Completion Date:

April 2013

Related Keywords:

  • Bladder Transitional Cell Carcinoma Stage IV
  • urothelial carcinoma
  • bladder cancer
  • vinflunine
  • transitional cell carcinoma
  • advanced or metastatic
  • unfit
  • ineligible to cisplatin
  • renal impairment
  • renal insufficiency
  • urologic neoplasms
  • urogenital neoplasm
  • urinary neoplasms
  • cisplatin
  • tubulin inhibitors
  • Carcinoma
  • Carcinoma, Transitional Cell