With 4,600 new cases in France in 2012, ovarian cancer is the seventh most common cancer in women and the fourth cause of mortality by cancer. Despite a high response rate to initial treatment, most patients will relapse within 2 years. No standard treatment has yet been established for patients with recurrent ovarian cancer. Most patients with such recurrences are currently treated with new combinations of systemic chemotherapy. A repeated laparotomy with complete cytoreduction is also an option that several authors have used to obtain median survival rates of more than 30 months. Twenty five percent of patients experiencing relapse present with platinum-resistant recurrence, occurring less than 6 months after chemotherapy completion. Recently, Pujade et al. showed that adding bevacizumab to chemotherapy significantly improves progression-free survival (PFS) in this subgroup of patients with poor prognoses (16.6 months versus 13.3 months in women treated with chemotherapy alone). Three case control studies have compared systemic chemotherapy and CRS (Cytoreduction Surgery) alone versus CRS plus HIPEC in patients with recurrent disease. They showed significantly improved results with the addition of HIPEC. In the French registry that included 474 patients with recurrence and peritoneal carcinomatosis, the median PFS was 13.8 months for platinum-resistant patients and 13 months for platinum-sensitive patients. Our hypothesis is that surgery would reduce the tumor burden and consequently the number of platinum-resistant tumor clones and that HIPEC would control the microscopic residual disease by increasing the tumor cell cytotoxicity. We assume that adding a locoregional treatment to an "Aurelia-like" systemic treatment would improve the PFS. We aim to assess the benefit of adding surgery and HIPEC to the treatment of first or second platinum-resistant recurrence compared to chemotherapy + bevacizumab.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
132
Cytoreductive surgery combined with HIPEC (Cisplatin 70 mg/m2).
Chemotherapy and bevacizumab (CT-BEV) 15 mg/kg once every 3 weeks from enrollment until disease progression (RECIST 1.1)
Centre Hospitalier Universitaire Jean Minjoz
Besançon, France
Centre Hospitalier Universitaire Jean Minjoz
Besançon, France
Centre Oscar Lambret
Lille, France
CHRU Claude Huriez
Lille, France
Centre Léon Bérard
Lyon, France
Centre Léon Bérard
Lyon, France
Institut du Cancer de Montpellier
Montpellier, France
Institut du Cancer de Montpellier
Montpellier, France
Centre Hospitalier Universitaire L'Archet II
Nice, France
Centre Hospitalier Universitaire L'Archet II
Nice, France
...and 12 more locations
Progression free survival
Progression will be based on RECIST V1.1 criteria performed on thoraco-abdominopelvic tomodensitometry (TDM ) assessed every 3 months. There is a follow-up period of 36 months.
Time frame: Change from baseline to 36 months
Overall survival
There is a follow-up period of 36 months.
Time frame: From the randomization to the death or 36 months end of follow-up
Potential treatment-related mortality
Reported only in the experimental arm (cytoreductive surgery + HIPEC)
Time frame: During the first 60 postoperative days
Potential treatment-related morbidity
Adverse events (AE) during the follow-up period: safety and tolerability will be assessed in terms of AEs, deaths, laboratory data, and vital signs. AEs will be described using MedDRA terms (version 18.0) and graded according to Common Terminology Criteria for Adverse Events (CTCAE version 5.0). These will be collected for all randomized patients.
Time frame: During the first 60 postoperative days
Quality of life assessment
Quality of Life will be assessed using the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) for all randomized patients.
Time frame: Baseline to 36 months end of follow-up
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