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

Ovarian Cancer Clinical Trial

— CHIPPI  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03842982
• Other study ID #: CHIPPI-1808
• Secondary ID: 2018-003680-62
• Status: Recruiting
• Phase: Phase 3
• Start date: April 1, 2019
• Est. completion date: August 1, 2028

Study information

• Verified date: December 2022
• Source: Centre Oscar Lambret
• Contact: Marie VANSEYMORTIER
• Phone: +33 3 20 29 59 18
• Email: promotion[@]o-lambret.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 362
• Est. completion date: August 1, 2028
• Est. primary completion date: August 1, 2027
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 76 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Fever
• Hyperthermia
• Ovarian Cancer
• Ovarian Carcinoma
• Ovarian Neoplasms
• Ovary Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Belgium	Cliniques universitaires St-Luc, Institut Roi Albert II	Bruxelles
France	Institut de Cancérologie de l'Ouest	Angers
France	Institut Bergonié	Bordeaux
France	Centre François Baclesse	Caen
France	Centre Jean Perrin	Clermont-Ferrand
France	Centre Oscar Lambret	Lille
France	Hôpital Jeanne de Flandre	Lille
France	Institut Paoli Calmettes	Marseille
France	ICM-Val d'Aurelle	Montpellier
France	Hôpital Européen Georges Pompidou	Paris
France	Centre Hospitalier Lyon Sud	Pierre-Bénite
France	Centre Henri Becquerel	Rouen
France	Clinique Mathilde	Rouen
France	Institut de Cancérologie de l'Ouest	Saint-Herblain
France	Hôpital de Hautepierre	Strasbourg
France	Institut de Cancérologie de Lorraine	Vandœuvre-lès-Nancy
France	Institut Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
Centre Oscar Lambret

Countries where clinical trial is conducted

Belgium,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall survival	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..
Secondary	Adverse events (AE)	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.
Secondary	Q-TWiST	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
Secondary	Quality of life of the patient (QLQC30)	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)
Secondary	Quality of life of the patient (QLQOV28)	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)