Clinical trial NCT03220932: Cytoreductive Surgery and HIPEC in First or Secondary Platinum-resistant Recurrent Ovarian Epithelial Cancer
Official title: Assessment of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in First or Secondary Platinum-resistant Recurrent Ovarian Epithelial Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Ovarian Epithelial Cancer
Keywords: Epithelial Ovarian Cancer - Platinum-resistant - Cytoreductive surgery - HIPEC - Quality of Life
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2017-07-18
Enrollment: 132
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed platinum-resistant Epithelial Ovarian Carcinoma (EOC)(clinical recurrence or persistence within 6 months of last treatment);
* White blood cells \>3,500/mm3, neutrophils ≥1,500/mm3, platelets ≥100,000/mm3;
* Good renal function: serum creatinine values \<1.5 mg/dl, creatinine clearance \>60 ml/min;
* Performance Status ≤2, Karnofsky Index ≥70%;
* Serum bilirubin ≤1.5 x Upper limit of normal (UNL) 2 mg/dl;
* Prior ovarian surgery before starting study treatment;
* Covered by a Healthcare System, where applicable, and/or in compliance with the recommendations of the national laws in force relating to biomedical research;
* Signed written informed consent obtained prior to any study-specific screening procedures.

Exclusion Criteria:

* Platinum-refractory EOC (i.e progression under platinum containing chemotherapy);
* Any prior malignancy not considered in complete remission for at least 2 years;
* Pregnancy or breastfeeding;
* Untreated central nervous system disease or symptomatic central nervous system metastasis, history or evidence of thrombotic or hemorrhagic disorders within 6 months before first study treatment;
* Uncontrolled hypertension or active clinically significant cardiovascular disease;
* Females of childbearing age not using medically accepted contraceptive measures, as judged by the investigator;
* Contraindication to any drug contained in the chemotherapy regimen;
* Known contraindication to cisplatin
* Medical, geographical, sociological, psychological or legal conditions that would prevent the patient from completing the study or signing the informed consent;
* Any significant disease which, in the investigator's opinion, excludes the patient from the study;
* Under any administrative or legal supervision.

Primary outcomes:
measure: Progression free survival
timeFrame: Change from baseline to 36 months
Secondary outcomes:
measure: Overall survival
timeFrame: From the randomization to the death or 36 months end of follow-up
measure: Potential treatment-related mortality
timeFrame: During the first 60 postoperative days
measure: Potential treatment-related morbidity
timeFrame: During the first 60 postoperative days
measure: Quality of life assessment
timeFrame: Baseline to 36 months end of follow-up
Other outcomes:
Locations:
city: Besançon
country: France
facility: Centre Hospitalier Universitaire Jean Minjoz
city: Besançon
country: France
facility: Centre Hospitalier Universitaire Jean Minjoz
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lille
country: France
facility: CHRU Claude Huriez
city: Lyon
country: France
facility: Centre Léon Bérard
city: Lyon
country: France
facility: Centre Léon Bérard
city: Montpellier
country: France
facility: Institut du Cancer de Montpellier
city: Montpellier
country: France
facility: Institut du Cancer de Montpellier
city: Nice
country: France
facility: Centre Hospitalier Universitaire L'Archet II
city: Nice
country: France
facility: Centre Hospitalier Universitaire L'Archet II
city: Nice
country: France
facility: Centre Hospitalier Universitaire L'Archet II
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou - APHP
city: Pierre-benite
country: France
facility: Centre Hospitalier Lyon Sud
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Poitiers
country: France
facility: Centre Hospitalier Universitaire de Poitiers
city: Saint-priest-en-jarez
country: France
facility: Centre Hospitalier Universitaire de St Etienne
city: Saint-Priest-en-Jarez
country: France
facility: Centre Hospitalier Universitaire de St Etienne
city: Saint-Priest-en-Jarez
country: France
facility: Institut de Cancérologie de la Loire
city: Strasbourg
country: France
facility: Centre Hospitalier Universitaire Hautepierre
city: Strasbourg
country: France
facility: Centre Hospitalier Universitaire Hautepierre
city: Strasbourg
country: France
facility: Centre Hospitalier Universitaire Hautepierre
city: Vandœuvre-lès-Nancy
country: France
facility: Institut de Cancérologie de Lorraine - Alexis Vautrin
Study officials:
References: