Using heated chemotherapy during surgery for ovarian cancer treatment

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 study is testing whether using heated chemotherapy during surgery can help women with ovarian cancer live longer and have fewer problems after treatment.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 362 (estimated)
• Ages: 18 Years to 76 Years
• Sex: Female
• Sponsor: Centre Oscar Lambret (other)
• Drugs / interventions: bevacizumab, chemotherapy
• Locations: 17 sites (Bruxelles and 16 other locations)
• Trial ID: NCT03842982 on ClinicalTrials.gov

What this trial studies

This phase III, multicenter, interventional study evaluates the effectiveness of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) when combined with either Primary Debulking Surgery (PDS) or Interval Debulking Surgery (IDS) in patients diagnosed with ovarian cancer. The primary goal is to assess disease-free survival (DFS) rates, while secondary objectives include evaluating overall survival (OS), morbidity associated with HIPEC, and its impact on quality of life. The study also aims to explore the residual viable cell count in abdominal drainage fluids and establish a biobank for future research.

Who should consider this trial

Good fit: Ideal candidates are women aged 18 to 76 with histologically confirmed primary epithelial ovarian carcinoma at FIGO stage III eligible for PDS or IDS.

Not a fit: Patients with non-epithelial ovarian tumors or those outside the specified age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve disease-free survival and overall quality of life for patients with ovarian cancer.

How similar studies have performed: Previous studies have shown promising results with HIPEC in similar contexts, indicating potential for success in this approach.

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

Where this trial is running

Bruxelles and 16 other locations

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

Study contacts

• Study coordinator: Marie VANSEYMORTIER

Conditions: Ovary Neoplasms, Ovarian Cancer, Ovarian Carcinoma, Ovarian cancer, Hyperthermic intraperitoneal chemotherapy, HIPEC, Primary Debulking Surgery, Interval Debulking Surgery