Clinical trial NCT03842982: Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Ovarian Cancer (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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Ovary Neoplasms
Ovarian Cancer
Ovarian Carcinoma
Keywords: Ovarian cancer
Hyperthermic intraperitoneal chemotherapy
HIPEC
Primary Debulking Surgery
Interval Debulking Surgery
Lead sponsor: Centre Oscar Lambret
Sponsor class: OTHER
First posted: 2019-02-15
Enrollment: 362
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 76
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Eligibility 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

Primary outcomes:
measure: Disease-free Survival (DFS)
timeFrame: 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 outcomes:
measure: Overall survival
timeFrame: From randomization to first progression, relapse or death from any cause , whichever came first, assessed up to 5 years..
measure: Adverse events (AE)
timeFrame: Covers the whole treatment duration from Randomization up to the end of treatment (surgery or CT) plus 30 days.
measure: Q-TWiST
timeFrame: Over the 5 year surveillance period
measure: Quality of life of the patient (QLQC30)
timeFrame: Up to 2 years after the end of treatment (every 3 month)
measure: Quality of life of the patient (QLQOV28)
timeFrame: Up to 2 years after the end of treatment (every 3 month)
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Cliniques universitaires St-Luc, Institut Roi Albert II
city: Angers
country: France
facility: Institut de Cancérologie de l'Ouest
city: Bordeaux
country: France
facility: Institut Bergonié
city: Caen
country: France
facility: Centre François Baclesse
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lille
country: France
facility: Hôpital Jeanne de Flandre
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Montpellier
country: France
facility: ICM-Val d'Aurelle
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Rouen
country: France
facility: Clinique Mathilde
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint-Herblain
country: France
facility: Institut de Cancérologie de l'Ouest
city: Strasbourg
country: France
facility: Hôpital de Hautepierre
city: Vandœuvre-lès-Nancy
country: France
facility: Institut de Cancérologie de Lorraine
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Centre Oscar Lambret, Lille, France
name: Fabrice NARDUCCI, MD
role: STUDY_DIRECTOR
References: