Efficacy of Combination of Trastuzumab to Gemcitabine - Platinum Advanced or Metastatic Urothelial Carcinoma
- Conditions
- Recurrent Bladder CancerStage IV Bladder CancerTransitional Cell Carcinoma of the Bladder
- Interventions
- Registration Number
- NCT01828736
- Lead Sponsor
- Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 61
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B: Platinum+Gemcitabine+Trastuzumab Trastuzumab 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 Arm A: Platinum + Gemcitabine Gemcitabine 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 Arm A: Platinum + Gemcitabine Cisplatin 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 Arm A: Platinum + Gemcitabine Carboplatin 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 Arm B: Platinum+Gemcitabine+Trastuzumab Gemcitabine 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 Arm B: Platinum+Gemcitabine+Trastuzumab Cisplatin 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 Arm B: Platinum+Gemcitabine+Trastuzumab Carboplatin 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
- Primary Outcome Measures
Name Time Method Progression Free survival Participants will be followed from radomization until progression or death, up to 3 years
- Secondary Outcome Measures
Name Time Method Number of participants with adverse events as a measure of safety and tolerability Participants will be followed all along the study period, an expected average of 3 years Toxicity will be classify according to NCI-CTC criteria Version 2.0. Cardiac toxicity will be assessed according to the NYHA (New York Heart Association) criteria.
Overall survival Participants will be followed from randomization until death or lost of follow-up, up to 3 years Objective response rate Objective Response Rate will be assessed during treatment period, every 3 cycles, up to 7 months Quality of life 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 Quality of Life will be assessed according to the EORTC QLQ-C30 Version 3 questionnaire
Trial Locations
- Locations (15)
Curie Institute
🇫🇷Paris, France
Hôpital Européen Georges Pompidou
🇫🇷Paris, France
Centre Hospitalier Départemental de la Vendée
🇫🇷La Roche-sur-yon, France
CHU de Besançon
🇫🇷Besançon, France
Clinique Victor Hugo
🇫🇷Le Mans, France
CHU Hôpital La Timone
🇫🇷Marseille, France
Hôpital Jean Perrin
🇫🇷Clermont Ferrand, France
Clinique Hartmann
🇫🇷Neuilly-Sur-Seine, France
Cliniques saint Luc - Université Catholique de Louvain
🇧🇪Bruxelles, Belgium
CHU Hôpital Saint André
🇫🇷Bordeaux, France
Hôpital Saint Louis
🇫🇷Paris, France
Groupe Hospitalier Saint Joseph Paris
🇫🇷Paris, France
Hôpital Foch
🇫🇷Suresnes, France
Hôpital Cochin
🇫🇷Paris, France
Institut Paoli Calmettes
🇫🇷Marseille, France