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

December 6, 2022 updated by: Centre Oscar Lambret

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)

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.

Study Overview

Status

Recruiting

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

362

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

      • Angers, France, 49055
        • Recruiting
        • Institut de Cancérologie de l'Ouest
        • Contact:
        • 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:
          • Frederic BIGOT, MD
        • Sub-Investigator:
          • Margot NOBLECOURT, MD
        • Sub-Investigator:
          • Victor SIMMET, MD
        • Sub-Investigator:
          • Marion DE VRIES, MD
      • Bordeaux, France, 33076
      • Caen, France, 14076
        • Recruiting
        • Centre Francois Baclesse
        • Contact:
        • Principal Investigator:
          • Sandrine MARTIN-FRANCOISE, MD
        • Sub-Investigator:
          • Jean François LE BRUN, MD
        • Sub-Investigator:
          • Florence JOLY, MD
      • Clermont-Ferrand, France, 63011
        • Recruiting
        • Centre Jean Perrin
        • Contact:
        • 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
      • Lille, France, 59020
        • Recruiting
        • Centre Oscar Lambret
        • Sub-Investigator:
          • Delphine HUDRY, MD
        • Contact:
        • Principal Investigator:
          • Fabrice NARDUCCI, MD
        • Sub-Investigator:
          • Annick CHEVALIER-PLACE, MD
      • Lille, France, 59037
        • Recruiting
        • Hôpital Jeanne de Flandre
        • Contact:
        • 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
      • Marseille, France, 13273
        • Recruiting
        • Institut Paoli Calmettes
        • Contact:
        • 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
      • Montpellier, France, 34298
      • Paris, France, 75008
        • Recruiting
        • Hopital Europeen Georges Pompidou
        • Contact:
        • 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
      • Pierre-Bénite, France, 69495
        • Recruiting
        • Centre Hospitalier Lyon Sud
        • Contact:
        • Contact:
        • Principal Investigator:
          • Naoual BAKRIN, MD
        • Principal Investigator:
          • Witold GERTYCH, MD
        • Sub-Investigator:
          • Olivier GLEHEN, MD
        • Sub-Investigator:
          • Vahan KEPENEKIAN, MD
        • Sub-Investigator:
          • Pierre DESCARGUES, MD
        • Sub-Investigator:
          • Pierre-Adrien BOLZE, MD
      • Rouen, France, 76100
        • Recruiting
        • Clinique Mathilde
        • Contact:
        • 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
      • Rouen, France
        • Recruiting
        • Centre Henri Becquerel
        • Contact:
        • Principal Investigator:
          • Agathe CROUZET, MD
        • Sub-Investigator:
          • Julien CARRILHO, 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
      • Saint-Herblain, France, 44800
        • Withdrawn
        • Institut de Cancérologie de l'Ouest
      • Strasbourg, France
        • Not yet recruiting
        • Hopital de Hautepierre
        • Contact:
        • Sub-Investigator:
          • Thomas BOISRAME, MD
        • Principal Investigator:
          • Chérif AKLADIOS, MD
        • Sub-Investigator:
          • Lauriane EBERST, MD
      • Vandœuvre-lès-Nancy, France, 54519
        • Recruiting
        • Institut de Cancerologie de Lorraine
        • Contact:
        • 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
      • Villejuif, France, 94805
        • Withdrawn
        • Institut Gustave Roussy

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 76 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / 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.

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 Names:
  • 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
From randomization to first progression, relapse or death from any cause , whichever came first, assessed up to 5 years..
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.
Covers the whole treatment duration from Randomization up to the end of treatment (surgery or CT) plus 30 days.
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.
Over the 5 year surveillance period
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.
Up to 2 years after the end of treatment (every 3 month)
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.
Up to 2 years after the end of treatment (every 3 month)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2019

Primary Completion (Anticipated)

August 1, 2027

Study Completion (Anticipated)

August 1, 2028

Study Registration Dates

First Submitted

February 13, 2019

First Submitted That Met QC Criteria

February 14, 2019

First Posted (Actual)

February 15, 2019

Study Record Updates

Last Update Posted (Estimate)

December 7, 2022

Last Update Submitted That Met QC Criteria

December 6, 2022

Last Verified

December 1, 2022

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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