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

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ClinicalTrials.gov Identifier: NCT04055038
Recruitment Status : Not yet recruiting
First Posted : August 13, 2019
Last Update Posted : August 13, 2019
Sponsor:
Information provided by (Responsible Party):
Blokhin's Russian Cancer Research Center

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
Ovarian Cancer Ovarian Neoplasms Serous Adenocarcinoma BRCA1 Mutation BRCA2 Mutation Chemotherapy Drug: Platinum-Based Drug Drug: Conventional chemotherapy 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 164 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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)
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Estimated Study Start Date : September 1, 2019
Estimated Primary Completion Date : September 1, 2021
Estimated Study Completion Date : January 1, 2022


Arm Intervention/treatment
Experimental: 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.

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:

  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
Conventional chemotherapy




Primary Outcome Measures :
  1. Objective response rate (RR) according to RECIST 1.1 criteria [ Time Frame: 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.

  2. Overall survival defined as time from randomization to death from any reason; [ Time Frame: 1 year ]
    Primary outcome for Phase III part: 2. Overall survival defined as time from randomization to death from any reason


Secondary Outcome Measures :
  1. Progression-free survival [ Time Frame: 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;

  2. Overall survival [ Time Frame: 12 months ]
    Overall survival defined as time from randomization to death from any reason (for Phase II part only);

  3. Progression-free survival 2 (PFS2) [ Time Frame: 24 months ]
    PFS2 defined as time from randomization to second disease progression event according to RECIST 1.1 criteria or death from any reason;

  4. Objective response rate (RR) according to RECIST 1.1 criteria [ Time Frame: 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).



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   due to the nature of this disease only female participants are allowed
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04055038


Contacts
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Contact: Alexey Rumyantsev, MD +79100022255 alexeymma@gmail.com

Locations
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Russian Federation
N.N. Blokhin Cancer Research Center
Moscow, Russian Federation, 115478
Sponsors and Collaborators
Blokhin's Russian Cancer Research Center

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Responsible Party: Blokhin's Russian Cancer Research Center
ClinicalTrials.gov Identifier: NCT04055038     History of Changes
Other Study ID Numbers: PROC2019
First Posted: August 13, 2019    Key Record Dates
Last Update Posted: August 13, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Adenocarcinoma
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Cystadenocarcinoma, Serous
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Cystadenocarcinoma
Neoplasms, Cystic, Mucinous, and Serous