Efficacy of Platinum-based Chemotherapy in Platinum-resistant Ovarian Cancer) (EPITOC)

Blokhin's Russian Cancer Research Center

Status and phase: Unknown; Phase 3; Phase 2

Conditions: Ovarian Neoplasms; Chemotherapy; BRCA2 Mutation; Serous Adenocarcinoma; BRCA1 Mutation; Ovarian Cancer

Treatments: Drug: Conventional chemotherapy; Drug: Platinum-Based Drug

Study type: Interventional

Funder types: Other

Identifiers

NCT04055038

PROC2019

Details and patient eligibility

About

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

Full 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.

Enrollment: 164 estimated patients

Sex: Female

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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164 participants in 2 patient groups

Platinum-based chemotherapy

Experimental group

Description:

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.

Treatment:

Drug: Platinum-Based Drug

Non-platinum monochemotherapy

Active Comparator group

Description:

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.

Treatment:

Drug: Conventional chemotherapy