Ovarian Cancer, Ovarian Neoplasms, Serous Adenocarcinoma, BRCA1 Mutation, BRCA2 Mutation, Chemotherapy
Conditions
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.
Interventions
Reintroduction of platinum-based chemotherapy
Conventional chemotherapy
Sponsors
Blokhin's Russian Cancer Research Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (RR) according to RECIST 1.1 criteria | 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. |
| Overall survival defined as time from randomization to death from any reason; | 1 year | Primary outcome for Phase III part: 2. Overall survival defined as time from randomization to death from any reason |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival | 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; |
| Overall survival | 12 months | Overall survival defined as time from randomization to death from any reason (for Phase II part only); |
| Progression-free survival 2 (PFS2) | 24 months | 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 | 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). |
Countries
Russia
Contacts
Primary ContactAlexey Rumyantsev, MD
Outcome results
None listed