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

NCT04055038 | Unknown Phase 2 DMC

• 1 other identifier: PROC2019
• Study Type: interventional
• Target: 164
• Locations: 1 country
• Sites: 1

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

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Objective response rate (RR) according to RECIST 1.1 criteria

  Primary outcome for Phase II part: response rate to treatment according to RECIST1.1 criteria. For patients without measurable disease Rustin criteria is allowed.

  0-18 weeks

• Overall survival defined as time from randomization to death from any reason;

  Primary outcome for Phase III part: 2. Overall survival defined as time from randomization to death from any reason

  1 year

Secondary Outcomes (4)

• 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

Study Arms (2)

Platinum-based chemotherapy

EXPERIMENTAL

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.

Drug: Platinum-Based Drug

Non-platinum monochemotherapy

ACTIVE COMPARATOR

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.

Drug: Conventional chemotherapy

Interventions

Platinum-Based Drug DRUG

Reintroduction of platinum-based chemotherapy

Platinum-based chemotherapy

Conventional chemotherapy DRUG

Conventional chemotherapy

Non-platinum monochemotherapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Gender Eligibility Details: due to the nature of this disease only female participants are allowed
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Blokhin's Russian Cancer Research Center: lead

Study Sites (1)

N.N. Blokhin Cancer Research Center

Moscow, 115478, Russia

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Cystadenocarcinoma, Serous

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Cystadenocarcinoma; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Cystic, Mucinous, and Serous

Central Study Contacts

Alexey Rumyantsev, MD

CONTACT

+79100022255; alexeymma@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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)

Study Record Dates

• First Submitted: April 28, 2019
• First Posted: August 13, 2019
• Study Start: September 1, 2019
• Primary Completion: September 1, 2021
• Study Completion: January 1, 2022
• Last Updated: August 13, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)