Evaluating the Efficacy of Hyperthermic Intraperitoneal Treatment to Enhance the Sensitivity of Immune Checkpoint Inhibitor in Patients With Advanced Ovarian Cancer： A Single-arm Study

NCT ID: NCT07068178

Last Updated: 2025-07-16

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-31
• Study Completion Date: 2030-01-31

Brief Summary

Background:

Advanced ovarian cancer is a highly dangerous disease, and many patients lose their lives due to limited treatment effectiveness. Previous studies have shown that current immunotherapy (e.g., PD-1 inhibitors) has poor results in ovarian cancer. The research team discovered that adding "heated abdominal chemotherapy" (called HIPEC, which uses a heated drug solution to wash the abdomen) to standard chemotherapy helps patients better control tumors. Recent lab studies also found that HIPEC not only reduces "harmful cells" around tumors that block drug effectiveness but also makes immunotherapy drugs work better. Animal experiments further confirmed that combining HIPEC with immunotherapy improves outcomes. Therefore, the investigators aim to test a key question: Can HIPEC help immunotherapy drugs work more effectively in humans?

Study Details:

The study will conduct a small two-phase trial, planning to enroll 30 patients with advanced ovarian cancer (Stage IIIc-IVA). All participants will receive standard chemotherapy (paclitaxel + platinum drugs) combined with HIPEC and an immunotherapy drug (tislelizumab, a PD-1 inhibitor). The main goal is to check whether tumors are completely removed after surgery. Investigators will also track how long tumors stay under control, overall survival time, treatment safety, and use blood and tumor tissue tests to find biomarkers that predict treatment response.

Why This Matters:

The study hopes to identify a safe method to enhance immunotherapy effectiveness and offer improved outcomes for advanced ovarian cancer patients.

Detailed Description

Advanced ovarian cancer carries a high mortality rate, and improving prognosis remains a clinical challenge, particularly given the limited efficacy of immunotherapy observed in prior studies. Prior randomized controlled trial demonstrated that hyperthermic intraperitoneal chemotherapy (HIPEC) enhances the effects of neoadjuvant chemotherapy in ovarian cancer. Further preclinical studies revealed that HIPEC reduces cancer-associated fibroblasts (CAFs) in the tumor microenvironment, alleviates immunosuppressive phenotypes, and synergizes with immune checkpoint inhibitors (ICIs) in animal models. Building on this evidence, it is hypothesized that HIPEC sensitizes ovarian cancer to ICIs. This prospective single-arm trial employs a Simon's two-stage design to evaluate HIPEC combined with tislelizumab (an anti-PD-1 agent) and standard neoadjuvant chemotherapy (paclitaxel/platinum) in 30 patients with FIGO stage IIIc-IVA high-grade serous ovarian cancer. The primary endpoint is R0 resection rate, with secondary endpoints including progression-free survival, overall survival, safety, pathological response, and multi-omics biomarker exploration. The study aims to validate HIPEC's role in enhancing ICI efficacy and provide evidence for improving immunotherapy outcomes in advanced ovarian cancer.

Conditions

HIPEC; Ovarian Serous Adenocarcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ICI-HIPET

Patients received the following interventions: On Day 0, intravenous administration of tislelizumab (an anti-PD-1 immune checkpoint inhibitor) was initiated within 3 hours post-HIPEC. Tumor tissue samples were collected before HIPEC, at 30 minutes, 60 minutes, and 90 minutes (end of HIPEC). Serum samples were collected pre- and post-HIPEC. On Day 1, additional serum samples were collected 24 hours after HIPEC-ICI completion. From Days 2-3, patients underwent paclitaxel + carboplatin chemotherapy, with serum sampling repeated at 48 hours post-HIPEC-ICI. On Days 21 and 42, the second and third cycles of neoadjuvant chemotherapy (tislelizumab + paclitaxel + carboplatin) were administered intravenously.

Group Type: EXPERIMENTAL

ICI-HIPET

Intervention Type: DRUG

Patients received the following interventions: On Day 0, intravenous administration of tislelizumab (an anti-PD-1 immune checkpoint inhibitor) was initiated within 3 hours post-HIPEC. Tumor tissue samples were collected before HIPEC, at 30 minutes, 60 minutes, and 90 minutes (end of HIPEC). Serum samples were collected pre- and post-HIPEC. On Day 1, additional serum samples were collected 24 hours after HIPEC-ICI completion. From Days 2-3, patients underwent paclitaxel + carboplatin chemotherapy, with serum sampling repeated at 48 hours post-HIPEC-ICI. On Days 21 and 42, the second and third cycles of neoadjuvant chemotherapy (tislelizumab + paclitaxel + carboplatin) were administered intravenously.

Interventions

ICI-HIPET

Patients received the following interventions: On Day 0, intravenous administration of tislelizumab (an anti-PD-1 immune checkpoint inhibitor) was initiated within 3 hours post-HIPEC. Tumor tissue samples were collected before HIPEC, at 30 minutes, 60 minutes, and 90 minutes (end of HIPEC). Serum samples were collected pre- and post-HIPEC. On Day 1, additional serum samples were collected 24 hours after HIPEC-ICI completion. From Days 2-3, patients underwent paclitaxel + carboplatin chemotherapy, with serum sampling repeated at 48 hours post-HIPEC-ICI. On Days 21 and 42, the second and third cycles of neoadjuvant chemotherapy (tislelizumab + paclitaxel + carboplatin) were administered intravenously.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Diagnosed with FIGO stage IIIC-IVA high-grade serous ovarian adenocarcinoma (histologically confirmed).
• Aged 18-70 years.
• Life expectancy ≥12 months.
• CT Suidan score ≥7 and Fagotti score ≥8 (assessed by two independent gynecologic oncologists via laparoscopic evaluation).
• Adequate organ function:AST/ALT ≤2× upper limit of normal (ULN);Total bilirubin ≤1.5× ULN;Serum creatinine ≤1.5× ULN.
• No myelosuppression:Hemoglobin (Hb) ≥80 g/L,White blood cell count (WBC) ≥2.0×10⁹/L,Neutrophil count ≥1.0×10⁹/L,Platelet count ≥100×10⁹/L.
• Performance Status (PS) score 0-1.

Exclusion Criteria

• Partial or complete bowel obstruction.
• Intestinal fistula of any grade.
• Hydronephrosis unrelieved by ureteral stenting.
• History of organ transplantation.
• Inflammatory bowel disease.
• Active or history of autoimmune diseases (e.g., systemic lupus erythematosus).
• Prior immunotherapy (including cellular therapy) or use of immunomodulators.
• Brain metastases.
• Grade ≥3 venous thromboembolism.
• Active infections (e.g., tuberculosis).
• Prior pelvic/abdominal radiotherapy.
• Prior hyperthermic intraperitoneal chemotherapy (HIPEC) or thermotherapy.
• Grade ≥2 dysfunction of major organs (e.g., heart, liver, kidneys).
• Other malignancies within 5 years (except skin or thyroid cancer).
• Psychiatric disorders affecting compliance.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Jing Li

OTHER

Sponsor Role: lead

Responsible Party

Jing Li

Chief Physician

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guangzhou, Guangdong, China

Countries

China

Central Contacts

Jing Li, Doctor

Role: CONTACT

lijing228@mail.sysu.edu.cn

+86 17701927439

Facility Contacts

Erwei Song

Role: primary

lijing228@mail.sysu.edu.cn

Jing Li ext. +8615915893493

Other Identifiers

ICI-HIPET

Identifier Type: -

Identifier Source: org_study_id