Overview

This trial is active, not recruiting.

Conditions recurrent bladder cancer, stage iv bladder cancer, transitional cell carcinoma of the bladder
Treatments trastuzumab, gemcitabine, carboplatin, cisplatin
Phase phase 2
Target HER2
Sponsor Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie
Collaborator Roche Pharma AG
Start date February 2004
End date May 2013
Trial size 61 participants
Trial identifier NCT01828736, CVH-CT 02

Summary

A multicenter, randomized, Phase 2 trial to study the effectiveness and feasibility of association of trastuzumab with combination chemotherapy in advanced or metastatic bladder cancer patients. Combining monoclonal antibody therapy with combination chemotherapy may improve treatment efficacy on tumours overexpressed HER 2.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
Gemcitabine = 1 000 mg/m2 Day1 and Day8 given every 21 days IV + If Creatinin Clearance > 60 ml/min : Cisplatin = Day 1: 70 mg/m² given every 21 days If Creatinin Clearance < 60 ml/min : Carboplatin = Day 1: AUC 5 given every 21 days
gemcitabine dFdC
Given IV, 1000 mg/m² BSA on Day 1 and Day 8 every 21 days
carboplatin Carboplat
Given IV: AUC 5 on Day 1 every 21 days
cisplatin cis-Diamminedichloroplatinum(II)
Given IV, 70 mg/m² BSA on day 1 every 21 days
(Experimental)
Trastuzumab: Charging dose = 8mg/kg on day 1; then 6mg/kg every 21 days given IV + Gemcitabine = 1 000 mg/m2 Day1 and Day8 given every 21 days IV + If Creatinin Clearance > 60 ml/min : Cisplatin = Day 1: 70 mg/m² given every 21 days If Creatinin Clearance < 60 ml/min : Carboplatin = Day 1: AUC 5 given every 21 days
trastuzumab anti-c-erB-2
Bottles of 150 mg; Charging dose: 8mg/kg then 6mg/kg every 21 days given IV
gemcitabine dFdC
Given IV, 1000 mg/m² BSA on Day 1 and Day 8 every 21 days
carboplatin Carboplat
Given IV: AUC 5 on Day 1 every 21 days
cisplatin cis-Diamminedichloroplatinum(II)
Given IV, 70 mg/m² BSA on day 1 every 21 days

Primary Outcomes

Measure
Progression Free survival
time frame: Participants will be followed from radomization until progression or death, up to 3 years

Secondary Outcomes

Measure
Objective response rate
time frame: Objective Response Rate will be assessed during treatment period, every 3 cycles, up to 7 months
Number of participants with adverse events as a measure of safety and tolerability
time frame: Participants will be followed all along the study period, an expected average of 3 years
Quality of life
time frame: Quality of Life will be assessed during the study period, every 3 cycles (Arm A patients) or every 3 months (Arm B patients), up to 3 years
Overall survival
time frame: Participants will be followed from randomization until death or lost of follow-up, up to 3 years

Eligibility Criteria

Male or female participants from 18 years up to 80 years old.

Inclusion Criteria: - Transitional cell carcinoma of the urothelium or bladder histologically proven stage IV AJCC [locally advanced (T4b and / or N + M0) unresectable or metastatic (M1)] - Tumor and / or metastasis overexpressing HER2 immunohistochemistry (IHC 3 +) or IHC 2 + and FISH +. Centralized analysis. - Measurable disease with at least one lesion with a diameter> 2 cm for conventional methods (clinical examination, CT or MRI) or> 1 cm for the helical scanner. In case of single metastasis, metastatic disease should be histologically proven - Age ≥ 18 years and ≤80 years - Life expectancy> 3 months, - Index performance status <2 according to ECOG PS, - No prior chemotherapy other than adjuvant and / or neoadjuvant chemotherapy, without Herceptin ® and complete for more than 6 months (naive to any previous chemotherapy in the metastatic setting) - No radiotherapy within 4 weeks prior to inclusion, - Normal cardiac function as measured by ejection fraction (LVEF> 50%), - Blood and liver satisfactory constants: Hematological criteria: - Neutrophils> 1.5 x 109 / L, - Chips> 100 x 109 / L - Hemoglobin> 10 g / dL, Liver function: - Alkaline phosphatase (unless bone metastases) <2 x N - Total bilirubin <1.5 x N - transaminases (AST, ALT) <1.5 x N, renal Constants: - Creatinine clearance > 30 ml / min (Cockcroft and Gault, cf. Annex XV protocol) - Patient's written consent after full information. Exclusion Criteria: - Concurrent treatment with an experimental drug, participation in another clinical trial within <30 days - Patients previously treated with Herceptin ®, or another treatment targeting growth factors EGF (eg Iressa ®, Tarceva ®) - Existence of a severe pulmonary disease, liver or kidney is likely to be exacerbated by the treatment, - Other medical conditions: congestive heart failure or angina pectoris even if medically controlled failure, history of myocardial infarction before entering the trial, hypertension or uncontrolled arrhythmias, significant valvular disease, - Patient with dyspnoea at rest or requiring oxygen therapy or with respiratory failure, - Presence of a severe infection requiring antibiotics, - Presence of CNS metastases or meningeal - History of another malignancy uncured or cured for less than 5 years (except basal cell carcinoma, papillary thyroid carcinoma in situ of the cervix treated) - Pregnant or lactating or not using effective contraception Women, - For Cisplatin only: carrying a serious neurological disease, current events devices> NCI grade 2 neuropathy, hearing loss, creatinine clearance <60 ml / min, the patient can not support a patient hydration.

Additional Information

Official title Multicenter Randomized Phase 2 Trial of Gemcitabine - Platinum With or Without Trastuzumab in Advanced or Metastatic Urothelial Carcinoma With HER2 Overexpression
Principal investigator Stéphane Oudard, MD, PhD.
Trial information was received from ClinicalTrials.gov and was last updated in April 2013.
Information provided to ClinicalTrials.gov by Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie.