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

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

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 Overview

• Status: Recruiting
• Conditions: Neoadjuvant Chemotherapy; Hyperthermic Intraperitoneal Chemotherapy
• Intervention / Treatment: Procedure: HIPEC; Procedure: intravenous chemotherapy

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: miaofang Wu, Doctor; Phone Number: +8613828494674; Email: wmiaofang@mail.sysu.edu.cn

Study Locations

• China
  • Other (Non U.s.)
    • Guangzhou, Other (Non U.s.), China, 510000
      • Recruiting
      • Sun Yat-sen Memorial Hospital
      • Contact: miaofang Wu; Phone Number: +8613828494674; Email: wmiaofang@mail.sysu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NHIPEC; Treatment: Four tubes will be placed via the laparoscopic ports and HIPEC will be given within 24 hours after laparoscopic evaluation.	Procedure: HIPEC; 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.
Active Comparator: Intravenous NACT; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Investigators: Principal Investigator: Jing Li, Doctor, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: January 24, 2022
• First Submitted That Met QC Criteria: February 17, 2022
• First Posted (Actual): February 18, 2022

Study Record Updates

• Last Update Posted (Actual): February 18, 2022
• Last Update Submitted That Met QC Criteria: February 17, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: HIPEC; Neoadjuvant chemotherapy; High-grade serous ovarian cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Wounds and Injuries; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Body Temperature Changes; Heat Stress Disorders; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Hyperthermia; Fever
• Other Study ID Numbers: 2020-KY-050

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: After data publication

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No