Efficacy of Combination of Trastuzumab to Gemcitabine - Platinum Advanced or Metastatic Urothelial Carcinoma (CVH-CT02)

Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie

Status and phase: Completed; Phase 2

Conditions: Transitional Cell Carcinoma of the Bladder; Recurrent Bladder Cancer; Stage IV Bladder Cancer

Treatments: Drug: Cisplatin; Biological: Trastuzumab; Drug: Gemcitabine; Drug: Carboplatin

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01828736

CVH-CT 02

Details and patient eligibility

About

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.

Enrollment: 61 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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61 participants in 2 patient groups

Arm A: Platinum + Gemcitabine

Active Comparator group

Description:

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

Treatment:

Drug: Carboplatin

Drug: Gemcitabine

Drug: Cisplatin

Arm B: Platinum+Gemcitabine+Trastuzumab

Experimental group

Description:

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

Treatment:

Drug: Carboplatin

Drug: Gemcitabine

Biological: Trastuzumab

Drug: Cisplatin