Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Ovarian Cancer (CHIPPI)

Inclusion Criteria:

Pre-eligibility criteria to be checked before surgery for pre-registration

1. Age ≥18 years and ≤ 76 years

2. Histologically proven primary epithelial ovarian carcinoma or fallopian tubecarcinoma or peritoneal carcinoma (including serous papillary adenocarcinoma,clear-cell carcinoma, mucinous adenocarcinoma and endometrioid carcinoma)

3. Pre-therapeutic FIGO (International Federation of Gynecology and Obstetrics) stageIII

4. Patient eligible for

5. Primary Debulking Surgery (PDS) with planned adjuvant chemotherapy +/-bevacizumab or other targeted therapy

6. Or Interval Debulking Surgery (IDS) after neo-adjuvant chemotherapy +/-bevacizumab or other targeted therapy, with or without planned adjuvantchemotherapy +/- bevacizumab or other targeted therapy. In case of neo-adjuvantchemotherapy, surgery should be performed in a time interval of 3 to 5 weeks incase of chemotherapy without bevacizumab, and in a time interval of 4 to 6weeks if chemotherapy is combined with bevacizumab. The patient remainseligible for the study if surgery is delayed beyond the recommended timeinterval.

7. WHO (World Health Organization Performance Status) ≤ 2

8. Physical status score ASA (American Society of Anesthesiologists) ≤ 2

9. Adequate bone marrow and renal function, as evidenced by the following testsperformed within 7 days prior to surgery:

• Absolute Neutrophil Count (ANC) ≥1,500/mm3

• Platelets ≥100,000/mm3

• Aspartate aminotransferase (ALT)/ Alanine aminotransferase (ALT) ≤2.5 × upperlimit of normal (ULN) (≤5.0 × ULN in case of liver metastases)

• Total bilirubin ≤1.5 × ULN (except in case of Gilbert's disease)

• Creatinine clearance ≥ 60 mL/ min

8. Negative serum pregnancy test within 7 days prior to surgery for women ofchildbearing potential. For non-menopausal women, if no hysterectomy is planned,willing to accept the use of an effective contraceptive regimen during the treatmentperiod and at least 6 months after the end of treatment (surgery or adjuvantchemotherapy)

9. Absence of contraindication to receive the products used in this study (cisplatinand products used in neo-adjuvant/ adjuvant chemotherapy) according to the mostrecent SmPC (Summary of Product Characteristics) of these products

10. Patient is willing and able to comply with the protocol for the duration of thestudy including undergoing treatment and scheduled visits and examinations includingfollow-up

11. Signed written informed consent

12. Patient covered by the French or Belgian "Social Security" regime Criteria to bechecked per-operatively for confirmation of enrolment and randomization

13. Residual disease after surgery (cytoreduction score CC) CC-0 (no macroscopicresidue) or CC-1 (residue < 2.5 mm)

14. Per-operative hemorrhage < 2.5 L

15. Strictly less than 3 digestive resections performed during surgery

16. Diuresis maintained during surgery, without oliguria or anuria (per-operatorydiuresis ≥ 0,5 mL/ kg/ h)

Exclusion Criteria:

1. Benign disease, borderline disease, non epithelial ovarian carcinoma orcarcinosarcoma

2. Cirrhosis

3. Known hypersensitivity to any of the study drugs, study drug classes, or excipientsin the formulation

4. Auditory impairment

5. Dehydration or intercurrent disease that contraindicates hyperhydration (includingcardio-respiratory disease)

6. Other uncontrolled intercurrent disease including, but not limited to: diabetes;hypertension; symptomatic congestive heart or pulmonary failure; renal, hepatic orsevere gastrointestinal (associated with diarrhea) chronic disease

7. Any unresolved NCI-CTCAE Grade ≥ 2 toxicity from previous anticancer therapy (excluding alopecia)

8. Concomitant treatment with prophylactic phenytoin

9. Receipt of live attenuated vaccine, including yellow fever vaccine, within 30 daysprior to inclusion (and, if patient is enrolled, up to 30 days after the lastadministration of study treatment)

10. Pregnant or breastfeeding woman

11. Psychiatric illness or social situation that would limit compliance with studyrequirement, substantially increase the risk of side effects, or compromise theability of the patient to give written informed consent

12. Inability to comply with medical follow-up of the trial (geographical, social orpsychic reasons)

13. Person under guardianship