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

• ClinicalTrials.gov Identifier: NCT03842982
• Recruitment Status: Recruiting
• First Posted: February 15, 2019
• Last Update Posted: December 7, 2022
• Sponsor: Centre Oscar Lambret
• Information provided by (Responsible Party): Centre Oscar Lambret

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Ovary Neoplasms; Ovarian Cancer; Ovarian Carcinoma	Drug: HIPEC	Phase 3

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 362 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase III Randomized Clinical Trial Evaluating Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Ovarian Cancer Considering Two Different Settings: Primary Debulking Surgery (PDS) and Interval Debulking Surgery (IDS)
• Actual Study Start Date: April 1, 2019
• Estimated Primary Completion Date: August 1, 2027
• Estimated Study Completion Date: August 1, 2028

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Drug: 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.; Other Name: Hyperthermic intraperitoneal chemotherapy
No Intervention: 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.

Outcome Measures

Primary Outcome Measures :

1. Disease-free Survival (DFS) [ Time Frame: 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) ]
   The DFS will be measured to assess the efficacy of the combination treatment of surgery and HIPEC or standard care alone.

Secondary Outcome Measures :

1. Overall survival [ Time Frame: From randomization to first progression, relapse or death from any cause , whichever came first, assessed up to 5 years.. ]
   The overall survival will be measured to assess the efficacy of HIPEC in combination with standard care.
2. Adverse events (AE) [ Time Frame: Covers the whole treatment duration from Randomization up to the end of treatment (surgery or CT) plus 30 days. ]
   The adverse events (AE) are collected to evaluate the impact of HIPEC on the safety and on the feasibility of adjuvant treatment (if any) is planned after surgery.
3. Q-TWiST [ Time Frame: Over the 5 year surveillance period ]
   Q-Twist (Quality-adjusted time without symptoms of disease or toxicity) will be calculated from the survival tile (OS and DFS) and AE (adverse events) data.
4. Quality of life of the patient (QLQC30) [ Time Frame: Up to 2 years after the end of treatment (every 3 month) ]
   European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Score 30 (QLQ-C30) will be used to measure the quality of life of the patients.
5. Quality of life of the patient (QLQOV28) [ Time Frame: Up to 2 years after the end of treatment (every 3 month) ]
   European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Ovarian Cancer Module (QLQ-OV28) will be used to measure the quality of life of the patients.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 76 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Women with ovarian cancer
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Marie VANSEYMORTIER; +33 3 20 29 59 18; promotion@o-lambret.fr

Contact: Fabrice MULOT; +33 3 20 29 59 18; promotion@o-lambret.fr

Locations

Belgium

Cliniques universitaires St-Luc, Institut Roi Albert II; Recruiting

Bruxelles, Belgium, 1200

Contact: Florence FONTAINE +32 02 764 85 09 florence.fontaine@uclouvain.be

Contact: Karoline AMANN karoline.amann@uclouvain.be

France

Institut de Cancérologie de l'Ouest; Recruiting

Angers, France, 49055

Contact: Romuald WERNERT, MD romuald.wernert@ico.unicancer.fr

Principal Investigator: Romuald WERNERT, MD

Sub-Investigator: Pedro RARO, MD

Sub-Investigator: Valeria DE FRANCO, MD

Sub-Investigator: Augustin REYNARD, MD

Sub-Investigator: Patrick SOULIE, MD

Sub-Investigator: Sophie ABADIE-LACOURTOISIE, MD

Sub-Investigator: Paule AUGEREAU, MD

Sub-Investigator: Anne PATSOURIS, MD

Sub-Investigator: Elouen BOUGHALEM, MD

Sub-Investigator: Frédéric BIGOT, MD

Sub-Investigator: Margot NOBLECOURT, MD

Sub-Investigator: Victor SIMMET, MD

Sub-Investigator: Marion DE VRIES, MD

Institut Bergonié; Not yet recruiting

Bordeaux, France, 33076

Contact: Coriolan LEBRETON c.lebreton@bordeaux.unicancer.fr

Contact f.guyon@bordeaux.unicancer.fr

Centre François Baclesse; Recruiting

Caen, France, 14076

Contact: Sandrine MARTIN-FRANCOISE, MD marsa@baclessse.unicancer.fr

Principal Investigator: Sandrine MARTIN-FRANCOISE, MD

Sub-Investigator: Jean François LE BRUN, MD

Sub-Investigator: Florence JOLY, MD

Sub-Investigator: Emeline MERIAUX, MD

Centre Jean Perrin; Recruiting

Clermont-Ferrand, France, 63011

Contact: Christophe POMEL, MD christophe.pomel@clermont.unicancer.fr

Principal Investigator: Christophe POMEL, MD

Sub-Investigator: Caroline CORNOU, MD

Sub-Investigator: Sophie DUBOIS, MD

Sub-Investigator: Morgane MASSON, MD

Sub-Investigator: Marie-Ange MOURET-REYNIER, MD

Centre Oscar Lambret; Recruiting

Lille, France, 59020

Contact: Fabrice NARDUCCI, MD f-narducci@o-lambret.fr

Principal Investigator: Fabrice NARDUCCI, MD

Sub-Investigator: Delphine HUDRY, MD

Sub-Investigator: Eric LEBLANC, MD

Sub-Investigator: Cyril ABDEDDAIM, MD

Sub-Investigator: Annick CHEVALIER-PLACE, MD

Sub-Investigator: Alfred BASSIL, MD

Sub-Investigator: Charlotte BELLIER, MD

Sub-Investigator: Valérie CHEVALIER-EVAIN, MD

Sub-Investigator: Emilie KACZMAREK, MD

Sub-Investigator: Samira MAKHLOUFI, MD

Hôpital Jeanne de Flandre; Recruiting

Lille, France, 59037

Contact: Pierre COLLINET, MD, PhD pierre.collinet@chru-lille.fr

Principal Investigator: Pierre COLLINET, MD, PhD

Sub-Investigator: Clarisse EVENO, MD

Sub-Investigator: Jérôme PHALIPPOU, MD

Sub-Investigator: Christophe DESAUW, MD

Sub-Investigator: Anne PLOQUIN, MD

Institut Paoli Calmettes; Recruiting

Marseille, France, 13273

Contact: Eric LAMBAUDIE, MD, PhD lambaudiee@ipc.unicancer.fr

Principal Investigator: Eric LAMBAUDIE, MD, PhD

Sub-Investigator: Gilles HOUVENAEGHEL, MD

Sub-Investigator: Guillaume BLACHE, MD

Sub-Investigator: Laura SABIANI, MD

Sub-Investigator: Julien BARROU, MD

Sub-Investigator: Maria Antonietta CAPPIELLO, MD

Sub-Investigator: Magali PROVANSAL, MD

Sub-Investigator: Frédérique ROUSSEAU, MD

Sub-Investigator: Renaud SABATIER, MD

ICM-Val d'Aurelle; Recruiting

Montpellier, France, 34298

Contact: Pierre-Emmanuel COLOMBO, MD Pierre-Emmanuel.Colombo@icm.unicancer.fr

Principal Investigator: Pierre-Emmanuel COLOMBO, MD

Sub-Investigator: Sébastien CARRERE, MD

Sub-Investigator: Anne MOURREGOT, MD

Sub-Investigator: François QUENET, MD

Sub-Investigator: Philippe ROUANET, MD

Sub-Investigator: Olivia SGARBURA, MD

Sub-Investigator: Véronique D'HONDT, MD

Sub-Investigator: Michel FABBRO, MD

Hôpital Européen Georges Pompidou; Recruiting

Paris, France, 75008

Contact: Anne-Sophie BATS, MD anne-sophie.bats@aphp.fr

Principal Investigator: Anne-Sophie BATS, MD

Sub-Investigator: Nicolas DELANOY, MD

Sub-Investigator: Henri AZAIS, MD

Sub-Investigator: Enrica BENTIVEGNA, MD

Sub-Investigator: Meriem KOUAL, MD

Sub-Investigator: Huyên-Thu NGUYEN-XUAN, MD

Centre Hospitalier Lyon Sud; Recruiting

Pierre-Bénite, France, 69495

Contact: Naoual BAKRIN, MD naoual.bakrin@chu-lyon.fr

Contact: Witold GERTYCH, MD witold.gertych@chu-lyon.fr

Principal Investigator: Naoual BAKRIN, MD

Principal Investigator: Witold GERTYCH, MD

Sub-Investigator: Olivier GLEHEN, MD

Sub-Investigator: Vahan KEPENEKIAN, MD

Sub-Investigator: Benoit YOU, MD

Sub-Investigator: Pierre DESCARGUES, MD

Sub-Investigator: Pierre-Adrien BOLZE, MD

Clinique Mathilde; Recruiting

Rouen, France, 76100

Contact: Benoît RESCH, MD benoit.resch@clinique-mathilde.fr

Principal Investigator: Benoït RESCH, MD

Sub-Investigator: Marc BARON, MD

Sub-Investigator: Julien COGET, MD

Sub-Investigator: Clotilde HENNETIER, MD

Sub-Investigator: Morgane PERRIN, MD

Sub-Investigator: Jean Jacques TUECH, MD

Sub-Investigator: Alexandre MARQUE, MD

Sub-Investigator: Sandrine MEZZANI, MD

Sub-Investigator: Cécile HENNEBERT, MD

Centre Henri Becquerel; Recruiting

Rouen, France

Contact: Agathe CROUZET, MD agathe.crouzet@chb.unicancer.fr

Principal Investigator: Agathe CROUZET, MD

Sub-Investigator: Julien CARRILHO, MD

Sub-Investigator: Emmanuel DE GOURNAY, MD

Sub-Investigator: Albane POTEAU, MD

Sub-Investigator: Laetitia AUGUSTO, MD

Sub-Investigator: Sophie GOUERANT, MD

Sub-Investigator: Cécile GUILLEMET, MD

Sub-Investigator: Marianne LEHEURTEUR, MD

Sub-Investigator: Camille PETRAU, MD

Institut de Cancérologie de l'Ouest; Withdrawn

Saint-Herblain, France, 44800

Hôpital de Hautepierre; Not yet recruiting

Strasbourg, France

Contact: Chérif AKLADIOS, MD Cherif.AKlADlOS@chru-strasbourg.fr

Sub-Investigator: Thomas BOISRAME, MD

Principal Investigator: Chérif AKLADIOS, MD

Sub-Investigator: Lauriane EBERST, MD

Institut de Cancérologie de Lorraine; Recruiting

Vandœuvre-lès-Nancy, France, 54519

Contact: Frédéric MARCHAL, MD f.marchal@nancy.unicancer.fr

Principal Investigator: Frédéric MARCHAL, MD

Sub-Investigator: Yolanda FERNANDEZ DIEZ, MD

Sub-Investigator: Céline GAVOILLE, MD

Sub-Investigator: Marie-Christine KAMINSKY, MD

Sub-Investigator: Cécilia CERIBELLI, MD

Institut Gustave Roussy; Withdrawn

Villejuif, France, 94805

Sponsors and Collaborators

Centre Oscar Lambret

Investigators

• Study Director: Fabrice NARDUCCI, MD; Centre Oscar Lambret, Lille, France

More Information

• Responsible Party: Centre Oscar Lambret
• ClinicalTrials.gov Identifier: NCT03842982
• Other Study ID Numbers: CHIPPI-1808; 2018-003680-62 ( EudraCT Number )
• First Posted: February 15, 2019
• Last Update Posted: December 7, 2022
• Last Verified: December 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Centre Oscar Lambret:

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

Additional relevant MeSH terms:

Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Hyperthermia; Fever; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Endocrine System Diseases; Gonadal Disorders; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Body Temperature Changes; Heat Stress Disorders; Wounds and Injuries