Clinical trial NCT01376752: Hyperthermic Intra-Peritoneal Chemotherapy (HIPEC) in Relapse Ovarian Cancer Treatment
Official title: A Phase III Randomized Study Evaluating Hyperthermic Intra-Peritoneal Chemotherapy (HIPEC) in the Treatment of Relapse Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Ovarian Epithelial Cancer Recurrent
Lead sponsor: UNICANCER
Sponsor class: OTHER
First posted: 2011-06-20
Enrollment: 415
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: CHIPOR hypothesis is that the adjunction of platinum HIPEC in first relapsed epithelial ovarian cancer is able to improve the median Overall Survival (OS) by 12 months. In that hypothesis, with alpha risk of 5%, a power beta of 80%, during a 3 years period of inclusion and a 3 years follow-up, the number of patients to include is 404. Taking into account a 10% failure, an overall number of 444 patients is required.

Detailed description: The patient received before the surgery a second line chemotherapy, platinum-based regimen with either carboplatine-paclitaxel, or carboplatine-caelyx. At the end of the six courses IV chemotherapy, if the disease is still responding and if a complete cytoreductive surgery seems possible, the patient is included after signed informed consent and will be operated 5 to 8 weeks after the last second-line chemotherapy cycle.

So, during the surgery the patient will be randomized if the complete cytoreductive surgery is really done and will then receive:

* either treatment A = maximal cytoreductive surgery without HIPEC
* or treatment B = maximal cytoreductive surgery with HIPEC

The HIPEC will be done at the end of the surgery. At the end of cytoreductive surgery, tumor residual disease must be null or very limited (Sugarbaker completeness cytoreduction: CC0 (no residual)-CC1 (residual \< 0.25cm).

Two methods will be used for the HIPEC: Open or closed abdomen, depends on the site practice. Each site will use the same method during the study for all included patients.

Eligibility criteria: Inclusion Criteria:

* Patient age ≥ 18 years
* Performance Status WHO \< 2
* Initially treated for Epithelial Ovarian Carcinoma
* Patient with only peritoneal relapse occurred at least 6 month from the initial treatment, resectable without distant metastasis (with the exception of communicating pleura effusion, sensitive to platine-based second line chemotherapy and resectable lymph-nodes in the groin or retro peritoneal)
* Platinum based second-line chemotherapy before surgery with either carboplatine-paclitaxel, or carboplatine-caelyx
* Complete cytoreductive surgery
* The surgery has to be planned 5 to 8 weeks from the last 2nd of chemotherapy
* No hepatic failure, bilirubin ≤ 1,5 time the Normal limit, ASAT and ALAT ≤ 3 time the Upper Normal Limit
* No Renal insufficiency (serum creatinine \< 1,5 time the normal limit, creatinine clearance \> 80 mL/min). calculated with MDRD method
* Hematology function: PNN ≥ 1,5x10⁹/L, platelets ≥ 100x10⁹/L
* No contraindication to general anaesthesia for heavy surgery
* Patients having read, signed and dated Informed consent before any study procedure
* Childbearing patients have to take appropriate contraceptive methods during the treatment and until 6 months after the treatment

Exclusion Criteria:

* Patient age \<18 years
* Previous cancer in the last 5 years (except cutaneous baso-cellular epithelioma or uterine peripheral epithelioma)
* Hypersensitivity to Platinum compound
* Distant metastasis
* Use of anti-angiogenic treatment
* Patient with other concurrent severe life threatening disease
* The need to perform more than two segmental digestive resections during the CRS +/- HIPEC surgery
* Any progressive disease during the IV systemic second-line chemotherapy (platine-based)
* Incomplete cytoreductive surgery with macroscopical residual disease (Sugarbaker \> CC1)
* Early relapse: less than 6 mois after the end of the first treatment
* Ovarian tumor other than Epithelioma Ovarian Cancer
* Uncontrolled infection
* Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
* Clinically significant cardiovascular disease contraindicating the hyper hydratation, which is necessary for HIPEC
* Patient already treated with HIPEC for the ovarian cancer
* Individual deprived of liberty or placed under the authority of a tutor

Primary outcomes:
measure: overall survival
timeFrame: from randomization to death (up to 4 years)
Secondary outcomes:
measure: relapse free survival
timeFrame: from randomization to relapse (up to 4 years)
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Amiens
country: France
facility: CHU d'AMIENS
city: Angers
country: France
facility: Centre Paul Papin
city: Bordeaux
country: France
facility: Institut Bergonie
city: Brest
country: France
facility: Clinique Pasteur
city: Brest
country: France
facility: Polyclinique Kéraudren
city: Caen
country: France
facility: Centre Francois Baclesse
city: Clermont-ferrand
country: France
facility: Centre Jean Perrin
city: Dijon
country: France
facility: Centre hospitalier de Dijon
city: Grenoble
country: France
facility: CHU de Grenoble
city: Le Mans
country: France
facility: Clinique Victor Hugo
city: Le Mans
country: France
facility: Pôle Santé Sud
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lille
country: France
facility: CHU de Lille
city: Limoges
country: France
facility: Centre Hospitalier Universitaire Dupuytren
city: Lyon
country: France
facility: Centre Leon Berard
city: Lyon
country: France
facility: Centre Hopsitalier Lyon Sud
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Marseille
country: France
facility: AP-HM - Hôpital de la Timone
city: Montpellier
country: France
facility: CRLC Val d'Aurelle
city: Nice
country: France
facility: Centre Hospitalier Universitaire Nice
city: Paris
country: France
facility: Hopital Lariboisiere
city: Paris
country: France
facility: Hopital Tenon
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Paris
country: France
facility: Institut Curie
city: Poitiers
country: France
facility: CHU - Hôpital de la Milétrie
city: Saint-etienne
country: France
facility: Centre Hospitalier Universitaire Saint Etienne- Hopital Nord
city: Saint-herblain
country: France
facility: Ico-Centre Rene Gauducheau
city: Strasbourg
country: France
facility: CHU Hautepierre
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Vandoeuvre-les-nancy
country: France
facility: Centre Alexis Vautrin
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias I Pujol
Study officials:
affiliation: Centre rené Gauducheau, NANTES
name: Jean-Marc CLASSE
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brigand C, Monneuse O, Mohamed F, Sayag-Beaujard AC, Isaac S, Gilly FN, Glehen O. Peritoneal mesothelioma treated by cytoreductive surgery and intraperitoneal hyperthermic chemotherapy: results of a prospective study. Ann Surg Oncol. 2006 Mar;13(3):405-12. doi: 10.1245/ASO.2006.05.041. Epub 2006 Jan 30.
citation: Armstrong DK, Bundy B, Wenzel L, Huang HQ, Baergen R, Lele S, Copeland LJ, Walker JL, Burger RA; Gynecologic Oncology Group. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006 Jan 5;354(1):34-43. doi: 10.1056/NEJMoa052985.