efficacy of platinum-based chemotherapy in platinum-resistant ovarian cancer) (epitoc)

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

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

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.