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
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- R0 Resection Rate
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •(Excluded if any criterion is met)
- •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.
研究组 & 干预措施
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.
干预措施: ICI-HIPET (Drug)
结局指标
主要结局
R0 Resection Rate
时间窗: At interval debulking surgery (approximately 9-12 weeks after treatment initiation)
R0 resection rate refers to the proportion of patients achieving complete macroscopic tumor removal (no visible residual disease) during interval debulking surgery after three cycles of neoadjuvant chemotherapy. This is determined by the surgeon's intraoperative assessment of the pelvic and abdominal cavities for any gross residual lesions.
次要结局
- Rate of progression-free survival(From day 1 of treatment until progression/death, through study completion (up to 24months))
- Rate of overall survival(From completion of first neoadjuvant therapy until death from any cause, assessed up to 24 months)
- Pathological response rate(During pathological examination of omental tissue (within 2 weeks post-surgery))
- Radiological Response Rate(After 3 cycles of neoadjuvant therapy (approximately 9 weeks))
研究者
Jing Li
Chief Physician
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University