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)
Overview
- Phase
- Phase 2
- Intervention
- Platinum-Based Drug
- Conditions
- Ovarian Cancer
- Sponsor
- Blokhin's Russian Cancer Research Center
- Enrollment
- 164
- Locations
- 1
- Primary Endpoint
- Overall survival defined as time from randomization to death from any reason;
- Last Updated
- 6 years ago
Overview
Brief Summary
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
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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;
Exclusion Criteria
- •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;
Arms & Interventions
Platinum-based chemotherapy
This is an experimental arm of this study. Allowed therapeutic options: 1. 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); 2. Gemcitabine 1000 mg/m2 d 1, 8 + cisplatin 75 mg/m2 1 every 3 weeks; 3. Doxorubicin 40-50 mg/m2 d 1 + carboplatin AUC5 or cisplatin 60-75 mg/m2 d 1 every 3 weeks; 4. Topotecan 0.75 mg/m2 d 1-3 + cisplatin 60-75 mg/m2 or carboplatin AUC 4-5 d 1 every 3 weeks; 5. 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.
Intervention: Platinum-Based Drug
Non-platinum monochemotherapy
This is a control arm of this study. Allowed therapeutic options: 1. Paclitaxel 60-80 mg/m2 weekly (or day 1, 8, 15 every 4 weeks schedule); 2. Gemcitabine 1000 mg/m2 d 1, 8, 15 every 4 weeks; 3. Doxorubicin 50-60 mg/m2 d 1 every 3 weeks; 4. Topotecan 1,2-1,5 mg/m2 d 1-5 every 3 weeks; 5. 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.
Intervention: Conventional chemotherapy
Outcomes
Primary Outcomes
Overall survival defined as time from randomization to death from any reason;
Time Frame: 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
Time Frame: 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.
Secondary Outcomes
- 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)