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

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)

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

Study Overview

• Status: Unknown
• Conditions: Ovarian Neoplasms; Ovarian Cancer; Chemotherapy; BRCA1 Mutation; BRCA2 Mutation; Serous Adenocarcinoma
• Intervention / Treatment: Drug: Platinum-Based Drug; Drug: Conventional chemotherapy

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 Type: Interventional
• Enrollment (Anticipated): 164
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Alexey Rumyantsev, MD; Phone Number: +79100022255; Email: alexeymma@gmail.com

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 115478
    • N.N. Blokhin Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Progression-free survival (PFS) defined as time from randomization to disease progression according to RECIST 1.1 criteria or death from any reason;	12 months
Overall survival	Overall survival defined as time from randomization to death from any reason (for Phase II part only);	12 months
Progression-free survival 2 (PFS2)	PFS2 defined as time from randomization to second disease progression event according to RECIST 1.1 criteria or death from any reason;	24 months
Objective response rate (RR) according to RECIST 1.1 criteria	Response rate to treatment according to RECIST1.1 criteria. For patients without measurable disease Rustin criteria is allowed (only for Phase II part).	12 months

Collaborators and Investigators

• Sponsor: Blokhin's Russian Cancer Research Center

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2019
• Primary Completion (Anticipated): September 1, 2021
• Study Completion (Anticipated): January 1, 2022

Study Registration Dates

• First Submitted: April 28, 2019
• First Submitted That Met QC Criteria: August 12, 2019
• First Posted (Actual): August 13, 2019

Study Record Updates

• Last Update Posted (Actual): August 13, 2019
• Last Update Submitted That Met QC Criteria: August 12, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Cystadenocarcinoma; Neoplasms, Cystic, Mucinous, and Serous; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Cystadenocarcinoma, Serous
• Other Study ID Numbers: PROC2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No