Randomized, Multicenter, Phase II/III Study, Evaluating Fractionated Cisplatin Chemotherapy/Gemcitabine Versus Carboplatin/Gemcitabine in the Treatment of Advanced or Metastatic Urothelial Cancer With Impaired Renal Function.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 18
- 主要终点
- Phase II: Efficacy - Rate of non progression at the end of treatment (C6D21).
研究概览
简要总结
This is a phase II/III, multicenter, randomized study which includes 420 patients on six years + 3 years follow up. 92 patients will be included during the phase II ; additional 328 patients will be included.
Patients with an advanced or metastatic urothelial cancer with impaired renal function will be randomized in one of the two following chemotherapy arm:
- Fractionated Cisplatin + Gemcitabine.
- Carboplatin + Gemcitabine.
The main objective of the part II study will be to evaluate the efficacy and the safety of a chemotherapy with a doublet platinum salt compound/Gemcitabine with fractionated Cisplatin or Carboplatin in this population.
The main objective of the part III study will be to compare the efficacy in terms of overall survival of a chemotherapy with a doublet platinum salt/Gemcitabine with fractionated Cisplatin or Carboplatin in this population.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •. Age < or = 18 years, patients aged 75 years or more will benefit from a geriatric assessment.
- •. Advanced or metastatic urothelial cancer confirmed histologically or cytologically.
- •. Patients liable to receive a first -line chemotherapy for advanced or metastatic urothelial carcinoma.
- •. Measurable disease according to RECIST criteria V1.
- •. Patients who received neoadjuvant or adjuvant chemotherapy based on platinum salt must have completed treatment at least 6 months before entering the study.
- •. Performance status < or =
- •. Life expectancy > 3 months.
- •. Patients with creatinine clearance between 40 and 60 ml / min ( according to Cockcroft and Gault ).
- •. Patients having no contra-indication to overhydration.
- •. Satisfactory hematological tests: Neutrophils > 1.5 G / l Platelets > 150 G / l , hemoglobin ≥ 10 g / dl.
- •. Satisfactory liver function tests: total bilirubin < 1.5 x ULN (upper limit of normal), AST (aspartate aminotransferase) and ALT (alanine aminotransferase)<or = 2.5 x ULN (or 5 x ULN if liver metastases).
- •. In case of prior radiotherapy, a minimum of 14 days must relapse between the end of radiotherapy and study entry.
- •. For women of childbearing age , use an effective contraceptive method to study entry and for the duration of the study and 6 months after the last dose of study treatment ; For sexually active fertile men having a partner of childbearing age using effective contraception for the duration of the study and 6 months after the last dose of study treatment.
- •. Patient affiliated to a social security system in France.
- •. Patient signed informed consent before inclusion in the study and before any specific procedure for the study.
排除标准
- •. Any concomitant or previous malignancy within 5 years prior to the study ( with the exception of basal cell or squamous cell carcinoma in situ).
- •. Pregnant or lactating women.
- •. Patients with brain metastases or meningeal or symptoms suggestive of such secondary locations.
- •. Bisphosphonate or Denosumab treatment initiated within 28 days prior to randomization into the study or patient who have started such treatment during the study ( a bisphosphonate or denosumab treatment initiated within a period longer than 28 days before randomization may be continued without change during the study ).
- •. Other concomitant cancer (radiation therapy, radiopharmaceutical agent chemotherapy).
- •. Patients with uncontrolled infection.
- •. Patients with peripheral neuropathy grade> 1, whatever the origin or patients with hearing loss.
- •. Patient with unstable disease (eg: unstable diabetes, poorly controlled hypertension , congestive heart failure or myocardial infarction within 3 months prior to study entry).
- •. Known hypersensitivity to study drugs.
- •. Treatment with any other investigational drug within 30 days before inclusion.
- •. Any psychological condition , familial, sociological or geographical not to comply with medical monitoring and / or procedures in the study protocol.
- •. Patient protected by law.
研究组 & 干预措施
Carboplatin/Gemcitabine
干预措施: Carboplatin (Drug)
Carboplatin/Gemcitabine
干预措施: Gemcitabine (Drug)
Fractionated Cisplatin/Gemcitabine
干预措施: Fractionated Cisplatin (Drug)
Fractionated Cisplatin/Gemcitabine
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Phase II: Efficacy - Rate of non progression at the end of treatment (C6D21).
时间窗: 5 years.
Progression is defined according to RECIST (Response Evaluation Criteria in Solid Tumors) criteria V1.1.
Phase III: Overall survival (in months).
时间窗: 9 years.
Overall survival is defined as the time from randomization until death or last follow up news (censured data).
Phase II: Tolerance - Percentage of patients for whom at least one of the 3 defined tolerance criteria (see description) is observed.
时间窗: 5 years.
Defined tolerance criteria : * Postponement of chemotherapy \> or = 2 weeks. * Alteration of renal function. * Need to decrease twice Gemcitabine dose on day 1 for : NCI CTC (National Cancer Institut Common Toxicity Criteria) grade III or IV non-hematologic toxicity, hematologic toxicity.
次要结局
- Phase II and III: Pharmacogenetics, exploration of cytidine deaminase activity and study of its genetic polymorphisms.(Prior to the initial dose on cycle 1 day 1.)
- Phase II and III: Overall survival.(Phase II: 5 years ; Phase III: 9 years.)
- Phase II and III: Quality of life using the EORTC QLQ - C30 questionnaire (European Organization for research and treatment of Cancer - Quality of life questionnaire).(Phase II: 5 years ; Phase III: 9 years.)
- Phase II and III: Tolerance according to NCI toxicity scale (version 4.0).(Phase II: 5 years ; Phase III: 9 years.)
- Phase II and III: Objective response.(Phase II: 5 years ; Phase III: 9 years.)
- Phase II and III: Geriatric evaluation using questionnaires.(Phase II: 5 years ; Phase III: 9 years.)
- Phase II and III: Pharmacokinetics - Platin concentrations(At cycles 1 and 2 day 1 - 5 mn before the end of infusion, one hour after the end of infusion, 3 hours (arm A) or 4 hours (arm B) after the end of infusion.)
- Phase II and III: Progression free survival.(Phase II: 5 years ; phase III: 9 years.)
- Phase II and III: Time to treatment failure.(Phase II: 5 years ; Phase III: 9 years.)