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

Phase 2

Recruiting

• Conditions: Hyperthermic Intraperitoneal Chemotherapy; Neoadjuvant Chemotherapy
• Interventions: Procedure: intravenous chemotherapy; Procedure: HIPEC

• Registration Number: NCT05246020
• Lead Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-12-01
• Status Verified: 2022-01
• Study First Submitted: 2022-01-24
• Study First Submitted QC: 2022-02-17
• Last Update Submitted: 2022-02-17
• Study First Posted: 2022-02-18
• Last Update Posted: 2022-02-18
• Primary Completion: 2022-12-01
• Study Completion: 2024-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 80

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intravenous NACT	intravenous chemotherapy	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.
NHIPEC	HIPEC	Treatment: Four tubes will be placed via the laparoscopic ports and HIPEC will be given within 24 hours after laparoscopic evaluation.

Primary Outcome Measures

Name	Time	Method
chemotherapy response score(CRS) 3	At the end of cycle 3 NACT (each cycle is 21 days)	the proportion of chemotherapy response score 3, which means a better outcome

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Sun Yat-sen Memorial Hospital; 🇨🇳 Guangzhou, Other (Non U.s.), China