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

Centre Oscar Lambret

Status and phase: Enrolling; Phase 3

Conditions: Ovary Neoplasms; Ovarian Carcinoma; Ovarian Cancer

Treatments: Drug: HIPEC

Study type: Interventional

Funder types: Other

Identifiers

NCT03842982

2018-003680-62 (EudraCT Number)

CHIPPI-1808

Details and patient eligibility

About

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.

Full 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

Enrollment: 362 estimated patients

Sex: Female

Ages: 18 to 76 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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362 participants in 2 patient groups

Arm A (PDS or IDS + HIPEC)

Experimental group

Description:

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.

Treatment:

Drug: HIPEC

Arm B (PDS or IDS)

No Intervention group

Description:

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.