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

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University80 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Interventions

HIPECPROCEDURE

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.

intravenous chemotherapyPROCEDURE

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.

Eligibility

Sex: FEMALEMin age: 17 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. International Federation of Gynecology and Obstetrics(FIGO) stage IIIC-IVA, HGSOC 2. Patients with Fagotti score ≥8 3. Adequate kidney function (blood creatinine 58-96 µmol/L) 4. Adequate haematological function (haemoglobin ≥110g/L, leucocytes ≥4.0×109/L, neutrophils ≥2.0×109/L, platelets≥100×109/L) 5. 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) 6. World Health Organization(WHO) score 0-2 Exclusion Criteria: 1. Patients who had received chemotherapy, radiotherapy or any kind of targeted therapy. 2. Patients with complete intestine obstruction. 3. Expected life span ≤8 weeks. 4. Complicated with any other known malignancies. 5. Patients with poor cardiopulmonary function, which would limit compliance with study requirements.

Outcomes

Primary Outcomes

chemotherapy response score(CRS) 3

the proportion of chemotherapy response score 3, which means a better outcome

Time frame: At the end of cycle 3 NACT (each cycle is 21 days)

Secondary Outcomes

progression-free survival(PFS)

progression-free survival

Time frame: From date of randomization until the date of first documented progression, assessed up to 3 years

overall survival(OS)

overall survival

Time frame: 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)

Time frame: 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

Time frame: during the procedure