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

NCT03842982 | Active Not Recruiting Phase 3 DMC

• 3 other identifiers: CHIPPI-18082024-514706-31-012018-003680-62
• Study Type: interventional
• Target: 362
• Locations: 2 countries
• Sites: 18

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.

Conditions

Ovary Neoplasms; Ovarian Cancer; Ovarian Carcinoma

Keywords

Ovarian cancer; Hyperthermic intraperitoneal chemotherapy; HIPEC; Primary Debulking Surgery; Interval Debulking Surgery

Outcome Measures

Primary Outcomes (1)

• Disease-free Survival (DFS)

  The DFS will be measured to assess the efficacy of the combination treatment of surgery and HIPEC or standard care alone.

  From randomization to first progression, relapse or death from any cause, whichever came first, assessed up to 5 years. (Follow-up up to 5 years)

Secondary Outcomes (5)

• Overall survival

  From randomization to first progression, relapse or death from any cause , whichever came first, assessed up to 5 years..

• Adverse events (AE)

  Covers the whole treatment duration from Randomization up to the end of treatment (surgery or CT) plus 30 days.

• Q-TWiST

  Over the 5 year surveillance period

• Quality of life of the patient (QLQC30)

  Up to 2 years after the end of treatment (every 3 month)

• Quality of life of the patient (QLQOV28)

  Up to 2 years after the end of treatment (every 3 month)

Study Arms (2)

Arm A (PDS or IDS + HIPEC)

EXPERIMENTAL

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.

Drug: HIPEC

Arm B (PDS or IDS)

NO INTERVENTION

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.

Interventions

HIPEC 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.

Also known as: Hyperthermic intraperitoneal chemotherapy

Arm A (PDS or IDS + HIPEC)

Eligibility Criteria

• Age: 18 Years - 76 Years
• Gender Eligibility Details: Women with ovarian cancer
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pre-eligibility criteria to be checked before surgery for pre-registration
• Age ≥18 years and ≤ 76 years
• 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)
• Pre-therapeutic FIGO (International Federation of Gynecology and Obstetrics) stage III
• Patient eligible for
• Primary Debulking Surgery (PDS) with planned adjuvant chemotherapy +/- bevacizumab or other targeted therapy
• 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.
• WHO (World Health Organization Performance Status) ≤ 2
• Physical status score ASA (American Society of Anesthesiologists) ≤ 2
• 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

You may not qualify if:

• Benign disease, borderline disease, non epithelial ovarian carcinoma or carcinosarcoma
• Cirrhosis
• Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation
• Auditory impairment
• Dehydration or intercurrent disease that contraindicates hyperhydration (including cardio-respiratory disease)
• 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
• Any unresolved NCI-CTCAE Grade ≥ 2 toxicity from previous anticancer therapy (excluding alopecia)
• Concomitant treatment with prophylactic phenytoin
• Pregnant or breastfeeding woman
• 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
• Inability to comply with medical follow-up of the trial (geographical, social or psychic reasons)
• Person under guardianship

Sponsors & Collaborators

• Centre Oscar Lambret: lead

Study Sites (18)

Institut Jules Bordet

Brussels, 1070, Belgium

Location

Cliniques universitaires St-Luc, Institut Roi Albert II

Brussels, 1200, Belgium

Location

Institut de Cancérologie de l'Ouest

Angers, 49055, France

Location

Institut Bergonié

Bordeaux, 33076, France

Location

Centre François Baclesse

Caen, 14076, France

Location

Centre Jean Perrin

Clermont-Ferrand, 63011, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Hôpital Jeanne de Flandre

Lille, 59037, France

Location

Institut Paoli Calmettes

Marseille, 13273, France

Location

ICM-Val d'Aurelle

Montpellier, 34298, France

Location

Hôpital Européen Georges Pompidou

Paris, 75008, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Clinique Mathilde

Rouen, 76100, France

Location

Centre Henri Becquerel

Rouen, France

Location

Institut de Cancérologie de l'Ouest

Saint-Herblain, 44800, France

Location

Hôpital de Hautepierre

Strasbourg, France

Location

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, 54519, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Hyperthermic Intraperitoneal Chemotherapy

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Chemotherapy, Adjuvant; Combined Modality Therapy; Therapeutics; Drug Therapy; Hyperthermia, Induced

Study Officials

• Fabrice NARDUCCI, MD

  Centre Oscar Lambret, Lille, France

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2019
• First Posted: February 15, 2019
• Study Start: May 3, 2019
• Primary Completion (Estimated): February 1, 2031
• Study Completion (Estimated): February 1, 2031
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

BE (2); FR (16)