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

NCT ID: NCT03842982

Last Updated: 2025-09-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 362 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-01
• Study Completion Date: 2026-11-01

Brief Summary

This is a phase III, multicenter, interventional and randomized study which evaluates the use of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) coupled with either Primary Debulking Surgery (PDS) or Interval Debulking Surgery (IDS), in patients with ovarian cancer. This study aims to assess the efficacy, in terms of disease-free survival (DFS), the use of HIPEC combined with standard care (PDS or IDS) or standard care alone.

Detailed Description

The primary objective of this study is to assess the efficacy, in terms of disease-free survival (DFS), the use of HIPEC treatment combined with standard care (PDS or IDS) or standard care alone (PDS or IDS alone).

Secondary objectives of the study include:

• Evaluating the efficacy of HIPEC in terms of overall survival (OS) in combination with standard of care
• Evaluating the morbidity associated with HIPEC.
• Evaluating the trade-off between efficacy and morbidity using the Q-TWiST approach.
• Evaluating the impact of HIPEC in terms of quality of life.

Exploratory objectives (optional) include:

• Evaluating the impact of HIPEC on the count of residual viable cells (evaluated by flow cytometry) in abdominal drainage fluids for patients recruited in Centre Oscar Lambret only.
• Constituting a biobank (tumoral samples and blood samples) for future translational researches

Conditions

Ovary Neoplasms; Ovarian Cancer; Ovarian Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A (PDS or IDS + HIPEC)

Surgery (Primary Debulking Surgery (PDS) or Interval Debulking Surgery (IDS)) + Neo or Adjuvant chemotherapy (standard care) + HIPEC (hyperthermic intraperitoneal chemotherapy)

Patients in this experimental arm will receive surgery (either PDS or IDS) and Neo and/or Adjuvant chemotherapy (CT) (as per standard care) combined with HIPEC. Patients undergoing PDS will also be receiving 6 cycles adjuvant CT according to the standard care (ideally 6 weeks post-surgery).

Patient undergoing IDS will start with 6 cycles of neo-adjuvant CT with a 3 - 5 weeks washout period (4 - 6 weeks if administered Bevacizumab) prior to surgery. They may also undergo additional adjuvant CT post-surgery according to the standard care.

Group Type: EXPERIMENTAL

HIPEC

Intervention Type: DRUG

HIPEC protocol (ONLY Arm A) consisted in cisplatin 100mg/m2 intraperitoneally (IP), heated to 40°C for 90 minutes, along with an IV perfusion of sodium thiosulfate.

Administration of the dose should be according the following schedule:

• 50% of the dose at start of perfusion, 25% of the dose after 30 minutes from start of the perfusion and 25% of the dose after 60 minutes from start of the perfusion.
• The procedure takes 120 minutes with a 90-minute perfusion period. The IV perfusion of sodium thiosulfate is for renal protection. At the start of HIPEC procedure, 9 g/m2 in 200 ml of distilled water will be administered by IV over 15 to 30 minutes. It will be then followed by 12 g/m2 in 1 liter (1L) distilled water in a continuous IV for 6 hours.

Arm B (PDS or IDS)

Surgery (Primary Debulking Surgery (PDS) or Interval Debulking Surgery (IDS)) + Neo or Adjuvant chemotherapy ONLY (standard care, without HIPEC)

Patients in the control group will ONLY receive the standard care, which consists of surgery (PDS or IDS) with Neo and/or Adjuvant chemotherapy (CT). Patients undergoing PDS will be receiving 6 cycles adjuvant CT according to the standard care (ideally 6 weeks post-surgery).

Patient undergoing IDS will start with 6 cycles of neo-adjuvant CT with a 3 - 5 weeks washout period (4 - 6 weeks if administered Bevacizumab) prior to surgery. They may also undergo additional adjuvant CT post-surgery according to the standard care.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

HIPEC

HIPEC protocol (ONLY Arm A) consisted in cisplatin 100mg/m2 intraperitoneally (IP), heated to 40°C for 90 minutes, along with an IV perfusion of sodium thiosulfate.

Administration of the dose should be according the following schedule:

• 50% of the dose at start of perfusion, 25% of the dose after 30 minutes from start of the perfusion and 25% of the dose after 60 minutes from start of the perfusion.
• The procedure takes 120 minutes with a 90-minute perfusion period. The IV perfusion of sodium thiosulfate is for renal protection. At the start of HIPEC procedure, 9 g/m2 in 200 ml of distilled water will be administered by IV over 15 to 30 minutes. It will be then followed by 12 g/m2 in 1 liter (1L) distilled water in a continuous IV for 6 hours.

Intervention Type: DRUG

Other Intervention Names

Hyperthermic intraperitoneal chemotherapy

Eligibility Criteria

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 tube carcinoma 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) stage III

4. Patient eligible for

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

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

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

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

7. Adequate bone marrow and renal function, as evidenced by the following tests performed 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 × upper limit 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 of childbearing potential. For non-menopausal women, if no hysterectomy is planned, willing to accept the use of an effective contraceptive regimen during the treatment period and at least 6 months after the end of treatment (surgery or adjuvant chemotherapy)

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

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

11. Signed written informed consent

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

13. Residual disease after surgery (cytoreduction score CC) CC-0 (no macroscopic residue) 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-operatory diuresis ≥ 0,5 mL/ kg/ h)

Exclusion Criteria

1. Benign disease, borderline disease, non epithelial ovarian carcinoma or carcinosarcoma

2. Cirrhosis

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

4. Auditory impairment

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

6. Other uncontrolled intercurrent disease including, but not limited to: diabetes; hypertension; symptomatic congestive heart or pulmonary failure; renal, hepatic or severe 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 days prior to inclusion (and, if patient is enrolled, up to 30 days after the last administration of study treatment)

10. Pregnant or breastfeeding woman

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

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

13. Person under guardianship

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 76 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Centre Oscar Lambret

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fabrice NARDUCCI, MD

Role: STUDY_DIRECTOR

Centre Oscar Lambret, Lille, France

Locations

Institut Jules Bordet

Brussels, , Belgium

Site Status: RECRUITING

Cliniques universitaires St-Luc, Institut Roi Albert II

Brussels, , Belgium

Site Status: RECRUITING

Institut de Cancérologie de l'Ouest

Angers, , France

Site Status: RECRUITING

Institut Bergonié

Bordeaux, , France

Site Status: NOT_YET_RECRUITING

Centre François Baclesse

Caen, , France

Site Status: RECRUITING

Centre Jean Perrin

Clermont-Ferrand, , France

Site Status: RECRUITING

Centre Oscar Lambret

Lille, , France

Site Status: RECRUITING

Hôpital Jeanne de Flandre

Lille, , France

Site Status: RECRUITING

Institut Paoli Calmettes

Marseille, , France

Site Status: RECRUITING

ICM-Val d'Aurelle

Montpellier, , France

Site Status: RECRUITING

Hôpital Européen Georges Pompidou

Paris, , France

Site Status: RECRUITING

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Site Status: RECRUITING

Clinique Mathilde

Rouen, , France

Site Status: RECRUITING

Centre Henri Becquerel

Rouen, , France

Site Status: RECRUITING

Institut de Cancérologie de l'Ouest

Saint-Herblain, , France

Site Status: WITHDRAWN

Hôpital de Hautepierre

Strasbourg, , France

Site Status: RECRUITING

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, , France

Site Status: RECRUITING

Institut Gustave Roussy

Villejuif, , France

Site Status: WITHDRAWN

Countries

Belgium; France

Central Contacts

Marie VANSEYMORTIER

Role: CONTACT

promotion@o-lambret.fr

+33 3 20 29 59 18

Fabrice MULOT

Role: CONTACT

promotion@o-lambret.fr

+33 3 20 29 59 18

Facility Contacts

Gabriele LIBERALE, MD, PhD

Role: primary

garbiele.liberale@hubruxelles.be

Florence FONTAINE

Role: primary

florence.fontaine@uclouvain.be

+32 02 764 85 09

Karoline AMANN

Role: backup

karoline.amann@uclouvain.be

Romuald WERNERT, MD

Role: primary

romuald.wernert@ico.unicancer.fr

Coriolan LEBRETON

Role: primary

c.lebreton@bordeaux.unicancer.fr

Role: backup

f.guyon@bordeaux.unicancer.fr

Sandrine MARTIN-FRANCOISE, MD

Role: primary

marsa@baclessse.unicancer.fr

Christophe POMEL, MD

Role: primary

christophe.pomel@clermont.unicancer.fr

Fabrice NARDUCCI, MD

Role: primary

f-narducci@o-lambret.fr

Jerome PHALIPPOU, MD

Role: primary

jerome.phalippou@chru-lille.fr

Eric LAMBAUDIE, MD, PhD

Role: primary

lambaudiee@ipc.unicancer.fr

Pierre-Emmanuel COLOMBO, MD

Role: primary

Pierre-Emmanuel.Colombo@icm.unicancer.fr

Anne-Sophie BATS, MD

Role: primary

anne-sophie.bats@aphp.fr

Naoual BAKRIN, MD

Role: primary

naoual.bakrin@chu-lyon.fr

Witold GERTYCH, MD

Role: backup

witold.gertych@chu-lyon.fr

Benoît RESCH, MD

Role: primary

benoit.resch@clinique-mathilde.fr

Agathe CROUZET, MD

Role: primary

agathe.crouzet@chb.unicancer.fr

Chérif AKLADIOS, MD

Role: primary

Cherif.AKlADlOS@chru-strasbourg.fr

Frédéric MARCHAL, MD

Role: primary

f.marchal@nancy.unicancer.fr

Other Identifiers

2018-003680-62

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CHIPPI-1808

Identifier Type: -

Identifier Source: org_study_id