Efficacy of Neoadjuvant Hyperthermic Intraperitoneal Chemotherapy in Advanced High-grade Serous Ovarian Cancer (the NHIPEC Trial)

Study Overview
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Brief Summary
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Background: Neoadjuvant chemotherapy (NACT) is an important treatment option for patients with ovarian cancer. Although intravenous NACT can improve optimal resection rates and decrease surgical morbidity and mortality, these advantages do not translate into a survival benefit. Ovarian carcinoma is mainly confined to the peritoneal cavity, which makes it a potential target for hyperthermic intraperitoneal chemotherapy (HIPEC). Our previous study showed that HIPEC could be used in the neoadjuvant setting, which was named neoadjuvant HIPEC (NHIPEC). Since hyperthermia is an excellent chemosensitiser, we hypothesised that the combination of NHIPEC and intravenous NACT could show superior efficacy to intravenous NACT alone. Methods: This study is a single-centre, open-label, randomised (1:1 allocation ratio) phase 2 trial. A total of 80 patients will be randomly assigned into an experimental group (NHIPEC+intravenous NACT) or a control group (intravenous NACT). Patients in the experimental group will receive NHIPEC following laparoscopic evaluation, and four tubes will be placed via the laparoscopic ports, which will be used to administer NHIPEC. Then, perfusion with docetaxel (60-75 mg/m2) will be performed (43°C for 60 min, Day 0) followed by cisplatin (75 mg/m2, Day 1) infusion (43°C for 60 min) 24 hours later. After NHIPEC, two cycles of intravenous NACT will be given. Patients in the control group will receive three cycles of intravenous NACT. The primary endpoint is the proportion of patients who achieve a Chemotherapy Response Score (CRS) of 3 according to the CRS system. The secondary endpoints include progression-free survival, overall survival and the rates of complete resection and NHIPEC-related adverse events.

Official Title
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Efficacy of Neoadjuvant Hyperthermic Intraperitoneal Chemotherapy in Advanced High-grade Serous Ovarian Cancer (the NHIPEC Trial)：a Randomised Controlled Trial

Conditions
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Hyperthermic Intraperitoneal Chemotherapy, Neoadjuvant Chemotherapy

Intervention / Treatment
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* Procedure: HIPEC
* Procedure: intravenous chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: International Federation of Gynecology and Obstetrics(FIGO) stage IIIC-IVA, HGSOC Patients with Fagotti score ≥8 Adequate kidney function (blood creatinine 58-96 µmol/L) Adequate haematological function (haemoglobin ≥110g/L, leucocytes ≥4.0×109/L, neutrophils ≥2.0×109/L, platelets≥100×109/L) Adequate liver function (serum total bilirubin 3.4-22.2µmol/L, alanine aminotransferase (ALT) 7-40U/L, aspartate aminotransferase (AST) 13-35U/L, AST/ALT ≤1.5) World Health Organization(WHO) score 0-2 Exclusion Criteria: Patients who had received chemotherapy, radiotherapy or any kind of targeted therapy. Patients with complete intestine obstruction. Expected life span ≤8 weeks. Complicated with any other known malignancies. Patients with poor cardiopulmonary function, which would limit compliance with study requirements.

Ages Eligible for Study
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Minimum Age: 17 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The eligible patients will be randomised into an experimental group (NHIPEC +intravenous NACT) or a control group (intravenous NACT). Patients in the NHIPEC experimental group will receive NHIPEC and two cycles of intravenous NACT, while patients in the control group will receive three cycles of intravenous NACT. All patients will undergo IDS within 4weeks after the last cycle of NACT.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NHIPEC<br>Treatment: Four tubes will be placed via the laparoscopic ports and HIPEC will be given within 24 hours after laparoscopic evaluation. | Procedure: HIPEC<br>* Docetaxel (60-75mg/m2) perfusion solution will be infused into the peritoneal cavity through the tubes within 24 hours after the laparoscopic evaluation. Then, perfusate containing cisplatin (75 mg/m2) will be infused 24 hours later. NHIPEC will be administered at 43°C for a duration of 60min. Saline solution (3000mL) will be used to dissolve the drug, and it will be heated and circulated at a flow rate of 300-500 mL/min.<br>|
| Active Comparator: Intravenous NACT<br>Drug:Three cycles of intravenous NACT will be given in this group. The regimen of intravenous NACT is docetaxel 60-75mg/m2 followed by carboplatin area under curve(AUC) 5 for a 21-day cycle. | Procedure: intravenous chemotherapy<br>* Patients in the control group will receive three cycles of intravenous NACT. The regimen of intravenous NACT is docetaxel 60-75mg/m2 followed by carboplatin AUC 5 for a 21-day cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| chemotherapy response score(CRS) 3 | the proportion of chemotherapy response score 3, which means a better outcome | At the end of cycle 3 NACT (each cycle is 21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival(PFS) | progression-free survival | From date of randomization until the date of first documented progression, assessed up to 3 years | 
| overall survival(OS) | overall survival | From date of randomization until the time of death from any cause, assessed up to 3 years | 
| Rate of R0 resection | the R0 resection rate of interval debulking surgery(IDS) | At the end of cycle 3 NACT (each cycle is 21 days),when IDS is conducted | 
| NHIPEC-related adverse effects | the adverse effects of NHIPEC | during the procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIPEC, Neoadjuvant chemotherapy, High-grade serous ovarian cancer