Randomized Study of LAROTAXEL + Cisplatin (LC) vs. Gemcitabine + Cisplatin (GC) in the First Line Treatment of Locally Advanced/Metastatic Urothelial Tract or Bladder Cancer - CILAB

• Conditions: ocally Advanced/Metastatic Urothelial Tract or Bladder Cancer; MedDRA version: 9.1Level: LLTClassification code 10005003Term: Bladder cancer

• Registration Number: EUCTR2007-001943-23-NL
• Lead Sponsor: Sanofi-Aventis Recherche et Développement

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-10-24
• Last Update Posted: 3 July 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 900

Inclusion Criteria

- Patients with histology/cytology confirmed Transitional Cell Carcinoma (TCC) with locally advanced (T4b) or metastatic (lymph node or visceral) urothelial tract or bladder cancer.

- ECOG Performans Status < or = 1

- No prior palliative chemotherapy.
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

- Age < 18 years old.
- Disease localized only to the radiation fields without radiologically confirmed progression of the disease within the radiation fields after completion of prior radiotherapy.

PRIOR THERAPY:
-- Time (Neo)Adjuvant chemotherapy if < 6 months between end of (Neo)adjuvant chemotherapy and relapse
- Less than 6 weeks or 3 weeks respectively from prior radiotherapy or surgery to time of randomization. Patients pN+ with no residual disease after surgery are not eligible.
- Less than 6 weeks elapsed from prior radiotherapy (in case of palliative radiotherapy for pain or bleeding control 6-week interval is not mandatory providing the patient recovered from all toxicities) and less than 3 weeks from surgery to time of randomization. Patients pN+ with no residual disease after surgery are not eligible
- Treatment with an investigational agent within 4 weeks (6 weeks for immunotherapy) of study enrollment

BIOLOGICAL CRITERIA: - Bone marrow function as defined by absolute neutrophil count < 1.5 x 10e9/L, platelet < 75 x10e9/L, or hemoglobin < 9.0 g/dL.
- Alkaline phosphatase (AP) = 2.5 x UNL associated with AST/ALT > 2.5 x UNL, or AP > 2.5 x UNL and = 5.0 x UNL associated with AST/ALT > 1.5 UNL or AP > 5.0 x UNL
- Total Bilirubin > 1.0 x UNL - Creatinine > ou = 1.0 x UNL, or actual creatinine clearance < 60 ml/min if creatinine > 1.0 x UNL and < ou = 1.5 UNL

PAST or CURRENT HISTORY
- Symptomatic History or new evidence of brain metastases or leptomeningeal disease (...)
- History of another neoplasm. Patients with prior history of either non-metastatic non-melanoma skin cancers, carcinoma in situ of the cervix, or cancer cured by surgery, small field radiation or chemotherapy = 5 years prior to randomization, or treated patients with incidental protsate cancer (pT2, Gleason <=6), and PSA <+ 0.5 ng/ml at study entry will be eligible
- Prior cisplatin as (neo)adjuvant chemotherapy with cumulative dose> 300 mg/m² - Peripheral neuropathy > grade 1
- History of inflammatory bowel disease, significant bowel obstruction.
- History of hypersensitivity to platinum, gemcitabine, taxanes, polysorbate 80, or to compounds with similar chemical structures.
- Known human immunodeficiency virus (HIV) infection immunodeficiency-syndrome (AIDS)-related illness.
- Any other as active illness such as active uncontrolled infections, uncontrolled cardiac disease or hypertension, uncontrolled diabetes that would preclude safe administration of study therapy at the time of randomization (...)

CONCOMITANT TREATMENT
- Concurrent treatment with strong inhibitors of CYP P450 3A4 or patients planning to receive these treatments. For patients who were receiving treatment with such agents, a one-week washout period is required prior to randomization
- Concurrent treatment with strong inhibitors of cytochrome P450 2C8 (gemfibrozile) or patients planning to receive this treatment. For patients who were receiving treatment with such agent, a one-week washout period is required prior to randomization.
Others Refer to the Protocol.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare Overall Survival (OS) of patients administered Larotaxel in combination with cisplatin versus gemcitabine in combination with cisplatin for the treatment of locally advanced/metastatic urothelial tract or bladder cancer;Secondary Objective: - To compare Progression Free Survival (PFS), Objective Response Rate (ORR), time to definitive deterioration of PS, Duration of Response (DR), and time to definitive 5% weight loss of larotaxel in combination with cisplatin vs. gemcitabine combined with cisplatin.<br><br>- To assess the safety and tolerability of Larotaxel in combination with cisplatin and gemcitabine with cisplatin.<br><br>- To assess the pharmacokinetics of Larotaxel and cisplatin in this patient population (in selected centers).;Primary end point(s): Overall Survival (OS)