Randomized Phase II/III Trial to Assess the Efficacy of Platinum-based Chemotherapy vs Standard Non-platinum Therapy in Patients With Platinum-resistant Recurrent Ovarian Cancer (ROC)
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 164
- 试验地点
- 1
- 主要终点
- Overall survival defined as time from randomization to death from any reason;
研究概览
简要总结
This is a phase II/III randomized controlled trial to evaluate efficacy of platinum-based chemotherapy vs conventionally prescribed non-platinum monochemotherapy in patients with platinum-resistant ovarian cancer
详细描述
Recurrent ovarian cancer (ROC) is usually subdivided to platinum-sensitive (platinum-free interval [PFI] ≥6 mo.) and platinum-resistant ovarian cancer [PROC] (PFI <6 mo.) subtypes. Prognosis for the latter group is dismal and current guidelines recommend treating these patients with non-platinum based chemotherapy. However, the evidence behind this is quite unconvincing and according to recent data patients with non-platinum refractory platinum-resistant ovarian cancer could derive benefit from platinum rechallenge. This trial is designed for head-to-head comparison of platinum and non-platinum therapy efficacy in treatment of platinum-resistant ovarian cancer.
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 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Age 18-70 years;
- •Histologically confirmed epithelial ovarian cancer (excluding mucinous, clear-cell and low-grade subtypes);
- •Ovarian cancer recurrence within 3-6 months after completion of platinum-based chemotherapy (given to possible variability in follow-up practices and tumor growth kinetics patients with platinum-free interval ≥3 and <7 months will be considered platinum-resistant);
- •Platinum-free interval ≤12 months;
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤2;
- •Response to penultimate platinum-based chemotherapy defined as partial or complete response assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria or ≥50% reduction in CA-125 concentration for patients without measurable lesions;
- •Not refractory to penultimate platinum-based chemotherapy regimen (ie, the disease did not progress during platinum-based chemotherapy and within ≤3 months after its completion);
- •Patients received ≤3 lines of prior chemotherapy;
- •No central nervous system (CNS) metastatic involvement;
- •No severe and uncontrolled concomitant diseases;
- •Adequate organ function:
- •Bone marrow - hemoglobin ≥ 90 g/l; Neutrophils ≥1,5x109/l; Platelets ≥75x109/l);
- •Renal - estimated creatinine clearance ≥50 ml/min (determined by Cockcroft-Gault equation);
- •Hepatic - alanine aminotransferase (ALaT) & aspartate transaminase (ASaT) ≤3 upper limit of normal (ULN), total bilirubin ≤ 25 umol/l;
- •Known BRCA1/2 mutation status as it will be used for stratification;
- •Life expectancy >3 months;
- •Patient is willingly consent to participate in the trial and signed informed consent form
排除标准
- •Platinum-refractory ovarian cancer defined as disease progression during penultimate platinum-based chemotherapy or ≤3 month after its completion;
- •No response to penultimate platinum-based chemotherapy;
- •Mucinous, clear-cell or low-grade serous/endometrioid histology;
- •>3 lines of prior therapy lines for advanced ovarian cancer (prior maintenance endocrine therapy or poly ADP ribose polymerase (PARP) inhibitors is allowed);
- •Prior therapy with PARP-inhibitors and endocrine therapy as a treatment for progressive ovarian cancer;
- •Platinum-free interval >12 months;
- •Symptoms of bowel obstruction of any etiology;
- •Contraindications to platinum-based chemotherapy;
- •Planned administration of PARP inhibitors during or after this line of chemotherapy;
- •Life expectancy <3 months;
- •Uncontrolled and/or severe concomitant diseases (eg, uncontrolled diabetes mellitus, renal failure, hepatic failure, uncontrolled arterial hypertension, arrhythmia, heart failure);
- •Metastatic CNS involvement;
- •Neuropathy grade >2.
研究组 & 干预措施
Platinum-based chemotherapy
This is an experimental arm of this study. Allowed therapeutic options:
- Paclitaxel 60-80 mg/m2 + carboplatin area under curve (AUC) 2-2.7 d 1, 8, 15 every 3 or 4 weeks (Q3W or Q4W);
- Gemcitabine 1000 mg/m2 d 1, 8 + cisplatin 75 mg/m2 1 every 3 weeks;
- Doxorubicin 40-50 mg/m2 d 1 + carboplatin AUC5 or cisplatin 60-75 mg/m2 d 1 every 3 weeks;
- Topotecan 0.75 mg/m2 d 1-3 + cisplatin 60-75 mg/m2 or carboplatin AUC 4-5 d 1 every 3 weeks;
- Etoposide 100 mg once daily orally d 1-7 + cisplatin 60-75 mg/m2 d1 every 3 weeks.
Up to 6 cycles of chemotherapy will be administered to study participants allocated to this arm.
干预措施: Platinum-Based Drug (Drug)
Non-platinum monochemotherapy
This is a control arm of this study. Allowed therapeutic options:
- Paclitaxel 60-80 mg/m2 weekly (or day 1, 8, 15 every 4 weeks schedule);
- Gemcitabine 1000 mg/m2 d 1, 8, 15 every 4 weeks;
- Doxorubicin 50-60 mg/m2 d 1 every 3 weeks;
- Topotecan 1,2-1,5 mg/m2 d 1-5 every 3 weeks;
- Etoposide 100 mg once daily orally d 1-10 every 3 weeks.
Up to 6 cycles of chemotherapy will be administered to study participants allocated to this arm.
干预措施: Conventional chemotherapy (Drug)
结局指标
主要结局
Overall survival defined as time from randomization to death from any reason;
时间窗: 1 year
Primary outcome for Phase III part: 2. Overall survival defined as time from randomization to death from any reason
Objective response rate (RR) according to RECIST 1.1 criteria
时间窗: 0-18 weeks
Primary outcome for Phase II part: response rate to treatment according to RECIST1.1 criteria. For patients without measurable disease Rustin criteria is allowed.
次要结局
- Progression-free survival(12 months)
- Overall survival(12 months)
- Progression-free survival 2 (PFS2)(24 months)
- Objective response rate (RR) according to RECIST 1.1 criteria(12 months)