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Estudio fase II/III, multicéntrico, aleatorizado, doble ciego y comparativo en primera línea de tratamiento con vinflunina/gemcitabina vs. placebo/gemcitabina en pacientes con carcinoma urotelial de células transicionales (CCT) avanzado no elegibles para recibir tratamiento con cisplatino (VINCENT)A Multicenter, Randomized Double-Blind Phase II/III Study in the First-Line Treatment of Advanced Transitional Cell Carcinoma (TCC) of the Urothelium Comparing Vinflunine/Gemcitabine to Placebo/Gemcitabine in Patients who are Ineligible to Receive Cisplatin-Based Therapy - VINCENT

Phase 1
Conditions
Carcinoma urotelial de células transicionales (CCT) localmente avanzado o metastásico del urotelioLocally advanced or metastatic Transitional Cell Carcinoma (TCC) of the urothelium
MedDRA version: 8.1Level: LLTClassification code 10044412Term: Transitional cell carcinoma
Registration Number
EUCTR2005-003733-40-ES
Lead Sponsor
Bristol-Myers Squibb International Corporation
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
500
Inclusion Criteria

1) Provided signed written informed consent

Target population
2) Histologic diagnosis of predominantly locally advanced or metastatic transitional cell carcinoma (TCC) of the urothelium (urinary bladder, kidney, renal pelvis, or ureter);
3) Ineligibility for cisplatin-based therapy because of at least one of the following two medical conditions:
- Calculated creatinine clearance (Cockroft-Gault formula, see Appendix 3) = 60 mL/min; or,
- New York Heart Association Classification Stage III-IV Congestive Heart Failure (see Protocol Appendix 4);
4) Measurable disease documented by imaging with at least one uni-dimensional lesion;
5) ECOG performance status of 0, 1, or 2 (see Protocol Appendix 5);
6) The following laboratory parameters:
- Absolute Neutrophil Count = 1,500 mm3,
- Platelet count = 100,000 mm3,
- Serum total bilirubin = 1.5 x upper limit of normal (ULN),
- Transaminases = 2.5 x ULN [> 5 times ULN only in case of liver metastasis].
7) If patient received neoadjuvant or adjuvant chemotherapy, he/she must have documented relapse, = 6 months after the last dose of chemotherapy.

Age and Sex
8) Men and women = age 18 years of age
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Sex and Reproductive Status
1) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 12 weeks after the study.
2) WOCBP using a prohibited contraceptive method.
3) Women who are pregnant or breastfeeding.
4) Women with a positive pregnancy test on enrollment or prior to study drug administration.
5) Sexually active fertile men not using effective birth control during the study and up to 6 months after the study if their partners are women of child-bearing potential.

Target Disease Exceptions
6) Diagnosis of predominantly non-transitional cell carcinoma of the urothelium (adenocarcinoma, squamous cell carcinoma, small cell, or other) or TCC originating at sites other than the urothelium.
7) Patients in whom radiation or surgery is indicated.

Medical History and Concurrent Diseases
8) Previous systemic chemotherapy treatment for locally advanced or metastatic disease (intravesical treatment is allowed, as well as neoadjuvant and adjuvant chemotherapy that was completed = 6 months before documented PD).
9) Known brain metastases or leptomeningeal involvement. CT scans are not required unless there is clinical suspicion of central nervous system (CNS) disease.
10) National Cancer Institute Common Terminology Criteria for Adverse Events (NCI
CTCAE) (v. 3.0) = Grade 3 peripheral neuropathy.
11) Prior radiation to = 30% of the bone marrow (See Protocol Appendix 6).
12) Other serious illness or medical condition including:
- Infection requiring systemic anti-infective therapy,
- any medical condition that might be aggravated by treatment or which could not be controlled, for instance patients with unstable angina, patients with myocardial infarction within 6 months and/or poorly controlled hypertension.
13) Other malignancies except adequately treated basal carcinoma of the skin, in-situ prostrate cancer Gleason = 6, in-situ cervix carcinoma or any other tumor with a disease free interval = 5 years.
14) Psychological, familial, or sociological conditions which do not permit medical follow-up and/or compliance with the study protocol.

Physical and Laboratory Test Findings
15) Inadequate renal function defined by a serum creatinine clearance = 20 mL/min (Cockcroft-Gault formula, see Protocol Appendix 3).

Allergies and Adverse Drug Reactions
16) Prior allergic reaction to any vinca alkaloid.

Prohibited Therapies and/or Medications
17) Patients who require treatment with ketoconazole, itraconazole, ritonavir, amprenavir and indinavir.
18) Any concurrent chronic systemic immune therapy (including steroids), chemotherapy, radiation therapy, hormonal therapy (except for physiologic replacement), or any other investigational agent.

Other Exclusion Criteria
20) Prisoners or patients who are compulsorily detained

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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