Clinical trial NCT04055038: Efficacy of Platinum-based Chemotherapy in Platinum-resistant Ovarian Cancer) (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
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Ovarian Cancer
Ovarian Neoplasms
Serous Adenocarcinoma
BRCA1 Mutation
BRCA2 Mutation
Chemotherapy
Lead sponsor: Blokhin's Russian Cancer Research Center
Sponsor class: OTHER
First posted: 2019-08-13
Enrollment: 164
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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)
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Objective response rate (RR) according to RECIST 1.1 criteria
timeFrame: 0-18 weeks
measure: Overall survival defined as time from randomization to death from any reason;
timeFrame: 1 year
Secondary outcomes:
measure: Progression-free survival
timeFrame: 12 months
measure: Overall survival
timeFrame: 12 months
measure: Progression-free survival 2 (PFS2)
timeFrame: 24 months
measure: Objective response rate (RR) according to RECIST 1.1 criteria
timeFrame: 12 months
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: N.N. Blokhin Cancer Research Center
Study officials:
References: