Hyperthermic Intra-Peritoneal Chemotherapy (HIPEC) in Relapse Ovarian Cancer Treatment

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase III Randomized Study Evaluating Hyperthermic Intra-Peritoneal Chemotherapy (HIPEC) in the Treatment of Relapse Ovarian Cancer

Conditions
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Ovarian Epithelial Cancer Recurrent

Intervention / Treatment
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* Procedure: Maximal cytoreductive surgery
* Drug: HIPEC


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: maximal cytoreductive surgery without HIPEC<br>The participant will have a regular cytoreductive surgery without the adjunction of HIPEC. | Procedure: Maximal cytoreductive surgery<br>* Maximal cytoreductive surgery<br>|
| Experimental: maximal cytoreductive surgery with HIPEC<br>The participant will have a regular cytoreductive surgery, then the adjunction of HIPEC: hyperthermic cisplatin will be used at 75mg/m² | Procedure: Maximal cytoreductive surgery<br>* Maximal cytoreductive surgery<br>Drug: HIPEC<br>* HIPEC: Hyperthermic Intra-PEritoneal Chemotherapy. Administration of cisplatin at 75mg/m²<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | Follow-up of 4 years. | from randomization to death (up to 4 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| relapse free survival | Follow-up of 4 years. | from randomization to relapse (up to 4 years) |