Efficacy of Platinum-based Chemotherapy in Platinum-resistant Ovarian Cancer) (EPITOC)
Study Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Drug: Platinum-Based Drug
Reintroduction of platinum-based chemotherapy
|
| Active Comparator: 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. |
Drug: Conventional chemotherapy
Conventional chemotherapy
|
Outcome Measures
Primary Outcome Measures
- Objective response rate (RR) according to RECIST 1.1 criteria [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.
- Overall survival defined as time from randomization to death from any reason; [1 year]
Primary outcome for Phase III part: 2. Overall survival defined as time from randomization to death from any reason
Secondary Outcome Measures
- Progression-free survival [12 months]
Progression-free survival (PFS) defined as time from randomization to disease progression according to RECIST 1.1 criteria or death from any reason;
- Overall survival [12 months]
Overall survival defined as time from randomization to death from any reason (for Phase II part only);
- Progression-free survival 2 (PFS2) [24 months]
PFS2 defined as time from randomization to second disease progression event according to RECIST 1.1 criteria or death from any reason;
- Objective response rate (RR) according to RECIST 1.1 criteria [12 months]
Response rate to treatment according to RECIST1.1 criteria. For patients without measurable disease Rustin criteria is allowed (only for Phase II part).
Eligibility Criteria
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;
-
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
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;
-
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | N.N. Blokhin Cancer Research Center | Moscow | Russian Federation | 115478 |
Sponsors and Collaborators
- Blokhin's Russian Cancer Research Center
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PROC2019