Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03842982
Recruitment Status : Recruiting
First Posted : February 15, 2019
Last Update Posted : May 15, 2019
Sponsor:
Information provided by (Responsible Party):
Centre Oscar Lambret

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 432 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 : June 1, 2023
Estimated Study Completion Date : June 1, 2024


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.




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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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. 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 during surgery ≥ 1 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
  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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03842982


Contacts
Layout table for location contacts
Contact: Marie VANSEYMORTIER +33 3 20 29 59 18 promotion@o-lambret.fr
Contact: Valentine STEEN +33 3 20 29 59 18 promotion@o-lambret.fr

Locations
Layout table for location information
France
Centre François Baclesse Not yet recruiting
Caen, France, 14076
Contact: Dr Guillaume BABIN, MD       g.babin@baclessse.unicancer.fr   
Principal Investigator: Dr Guillaume BABIN, MD         
Sub-Investigator: DrJean François LE BRUN, MD         
Sub-Investigator: Dr Sandrine MARTIN-FRANCOISE, MD         
Sub-Investigator: Dr Florence JOLY, MD         
Sub-Investigator: Dr Emeline MERIAUX, MD         
Centre Jean Perrin Not yet recruiting
Clermont-Ferrand, France, 63011
Contact: Dr Christophe POMEL, MD       christophe.pomel@clermont.unicancer.fr   
Principal Investigator: Dr Christophe POMEL, MD         
Sub-Investigator: Dr Caroline CORNOU, MD         
Sub-Investigator: Dr Sophie DUBOIS, MD         
Sub-Investigator: Dr Morgane MASSON, MD         
Sub-Investigator: Dr Marie-Ange MOURET-REYNIER, MD         
Centre Oscar Lambret Recruiting
Lille, France, 59020
Contact: Dr Fabrice NARDUCCI, MD       f-narducci@o-lambret.fr   
Principal Investigator: Dr Fabrice NARDUCCI, MD         
Sub-Investigator: Dr Delphine HUDRY, MD         
Sub-Investigator: Dr Eric LEBLANC, MD         
Sub-Investigator: Dr Cyril ABDEDDAIM, MD         
Sub-Investigator: Dr Annick CHEVALIER-PLACE, MD         
ICM-Val d'Aurelle Not yet recruiting
Montpellier, France, 34298
Contact: Dr Pierre-Emmanuel COLOMBO, MD       Pierre-Emmanuel.Colombo@icm.unicancer.fr   
Principal Investigator: Dr Pierre-Emmanuel COLOMBO, MD         
Sub-Investigator: Dr Sébastien CARRERE, MD         
Sub-Investigator: Dr Anne MOURREGOT, MD         
Sub-Investigator: Dr François QUENET, MD         
Sub-Investigator: Dr Philippe ROUANET, MD         
Sub-Investigator: Dr Olivia SGARBURA, MD         
Sub-Investigator: Dr Véronique D'HONDT, MD         
Sub-Investigator: Dr Michel FABBRO, MD         
Centre Hospitalier Lyon Sud Not yet recruiting
Pierre-Bénite, France, 69495
Contact: Dr Naoual BAKRIN, MD       naoual.bakrin@chu-lyon.fr   
Contact: Dr Witold GERTYCH, MD       witold.gertych@chu-lyon.fr   
Principal Investigator: Dr Naoual BAKRIN, MD         
Principal Investigator: Dr Witold GERTYCH, MD         
Sub-Investigator: Dr Olivier GLEHEN, MD         
Sub-Investigator: Dr Vahan KEPENEKIAN, MD         
Sub-Investigator: Dr Benoit YOU, MD         
Institut de Cancérologie de l'Ouest Not yet recruiting
Saint-Herblain, France, 44800
Contact: Dr Charlotte BOURGIN, MD       charlotte.bourgin@ico.unicancer.fr   
Principal Investigator: Dr Charlotte BOURGIN, MD         
Sub-Investigator: Dr Jean-Marc CLASSE, MD         
Sub-Investigator: Dr Cécile LOAEC, MD         
Sub-Investigator: Dr Dominique BERTON-RIGAUD, MD         
Sub-Investigator: Dr Emmanuelle BOURBOULOUX, MD         
Sub-Investigator: Dr Jean-Sébastien FRENEL, MD         
Sub-Investigator: Dr Carole GOURMELON, MD         
Institut de Cancérologie de Lorraine Not yet recruiting
Vandœuvre-lès-Nancy, France, 54519
Contact: Dr Frédéric MARCHAL, MD       f.marchal@nancy.unicancer.fr   
Principal Investigator: Dr Frédéric MARCHAL, MD         
Sub-Investigator: Dr Yolanda FERNANDEZ DIEZ, MD         
Sub-Investigator: Dr Céline GAVOILLE, MD         
Sub-Investigator: Dr Marie-Christine KAMINSKY, MD         
Institut Gustave Roussy Not yet recruiting
Villejuif, France, 94805
Contact: Dr Sébastien GOUY, MD       sebastien.gouy@gustaveroussy.fr   
Principal Investigator: Dr Sébastien GOUY, MD         
Sub-Investigator: Dr Alexandra LEARY, MD         
Sponsors and Collaborators
Centre Oscar Lambret
Investigators
Layout table for investigator information
Study Director: Dr Fabrice NARDUCCI, MD Centre Oscar Lambret, Lille, France

Layout table for additonal information
Responsible Party: Centre Oscar Lambret
ClinicalTrials.gov Identifier: NCT03842982     History of Changes
Other Study ID Numbers: CHIPPI-1808
2018-003680-62 ( EudraCT Number )
First Posted: February 15, 2019    Key Record Dates
Last Update Posted: May 15, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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:
Layout table for MeSH terms
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Fever
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Body Temperature Changes
Signs and Symptoms