Back to results

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

Primary Purpose

Ovarian Cancer, Ovarian Neoplasms, Serous Adenocarcinoma

Status

Unknown status

Phase

Phase 2

Locations

Russian Federation

Study Type

Interventional

Intervention

Platinum-Based Drug

Conventional chemotherapy

About this trial

This is an interventional treatment trial for Ovarian Cancer

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)FemaleDoes not accept 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.

Sites / Locations

N.N. Blokhin Cancer Research Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Platinum-based chemotherapy

Non-platinum monochemotherapy

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

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

Secondary Outcome Measures

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;

Overall survival

Overall survival defined as time from randomization to death from any reason (for Phase II part only);

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;

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).

Full Information

NCT ID

NCT04055038

First Posted

April 28, 2019

Last Updated

August 12, 2019

Sponsor

Blokhin's Russian Cancer Research Center

1. Study Identification

Unique Protocol Identification Number

NCT04055038

Brief Title

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

Acronym

EPITOC

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)

Study Type

Interventional

2. Study Status

Record Verification Date

August 2019

Overall Recruitment Status

Unknown status

Study Start Date

September 1, 2019 (Anticipated)

Primary Completion Date

September 1, 2021 (Anticipated)

Study Completion Date

January 1, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Blokhin's Russian Cancer Research Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

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)

Allocation

Randomized

Enrollment

164 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Platinum-based chemotherapy

Arm Type

Experimental

Arm Description

Arm Title

Non-platinum monochemotherapy

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Platinum-Based Drug

Intervention Description

Reintroduction of platinum-based chemotherapy

Intervention Type

Drug

Intervention Name(s)

Conventional chemotherapy

Intervention Description

Conventional chemotherapy

Primary Outcome Measure Information:

Title

Objective response rate (RR) according to RECIST 1.1 criteria

Description

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

Time Frame

0-18 weeks

Title

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

Description

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

Time Frame

1 year

Secondary Outcome Measure Information:

Title

Progression-free survival

Description

Progression-free survival (PFS) defined as time from randomization to disease progression according to RECIST 1.1 criteria or death from any reason;

Time Frame

12 months

Title

Overall survival

Description

Overall survival defined as time from randomization to death from any reason (for Phase II part only);

Time Frame

12 months

Title

Progression-free survival 2 (PFS2)

Description

PFS2 defined as time from randomization to second disease progression event according to RECIST 1.1 criteria or death from any reason;

Time Frame

24 months

Title

Objective response rate (RR) according to RECIST 1.1 criteria

Description

Response rate to treatment according to RECIST1.1 criteria. For patients without measurable disease Rustin criteria is allowed (only for Phase II part).

Time Frame

12 months

10. Eligibility

Sex

Female

Gender Based

Yes

Gender Eligibility Description

due to the nature of this disease only female participants are allowed

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Alexey Rumyantsev, MD

Phone

+79100022255

alexeymma@gmail.com

Facility Information:

Facility Name

N.N. Blokhin Cancer Research Center

City

Moscow

ZIP/Postal Code

115478

Country

Russian Federation

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

We'll reach out to this number within 24 hrs