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

NCT ID: NCT04055038

Last Updated: 2019-08-13

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 164 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-01
• Study Completion Date: 2022-01-01

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Platinum-Based Drug

Intervention Type: DRUG

Reintroduction of platinum-based chemotherapy

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.

Group Type: ACTIVE_COMPARATOR

Conventional chemotherapy

Intervention Type: DRUG

Conventional chemotherapy

Interventions

Platinum-Based Drug

Reintroduction of platinum-based chemotherapy

Intervention Type: DRUG

Conventional chemotherapy

Conventional chemotherapy

Intervention Type: DRUG

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;
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Blokhin's Russian Cancer Research Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

N.N. Blokhin Cancer Research Center

Moscow, , Russia

Countries

Russia

Central Contacts

Alexey Rumyantsev, MD

Role: CONTACT

alexeymma@gmail.com

+79100022255

Other Identifiers

PROC2019

Identifier Type: -

Identifier Source: org_study_id