Multicenter Randomized Phase 2 Trial of Gemcitabine - Platinum With or Without Trastuzumab in Advanced or Metastatic Urothelial Carcinoma With HER2 Overexpression
Overview
- Phase
- Phase 2
- Intervention
- Gemcitabine
- Conditions
- Recurrent Bladder Cancer
- Sponsor
- Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie
- Enrollment
- 61
- Locations
- 15
- Primary Endpoint
- Progression Free survival
- Status
- Completed
- Last Updated
- 9 years ago
Overview
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.
Investigators
Eligibility Criteria
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:
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.
Arms & Interventions
Arm A: Platinum + 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
Intervention: Gemcitabine
Arm A: Platinum + 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
Intervention: Carboplatin
Arm A: Platinum + 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
Intervention: Cisplatin
Arm B: Platinum+Gemcitabine+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
Intervention: Trastuzumab
Arm B: Platinum+Gemcitabine+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
Intervention: Gemcitabine
Arm B: Platinum+Gemcitabine+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
Intervention: Carboplatin
Arm B: Platinum+Gemcitabine+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
Intervention: Cisplatin
Outcomes
Primary Outcomes
Progression Free survival
Time Frame: Participants will be followed from radomization until progression or death, up to 3 years
Secondary Outcomes
- 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)
- 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)