A Phase 1/2a Study to Evaluate the Tolerance, Safety, Efficacy, and Pharmacokinetics of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) Using Paclitaxel for Platinum-resistant Recurrent Ovarian Cancer With Peritoneal Metastasis (PIPAC-OVPAC 1/2a)
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 53
- 主要终点
- Dose limiting toxicities
研究概览
简要总结
The purpose of this study is to evaluate the tolerance, safety, efficacy, and pharmacokinetics of pressurized intraperitoneal aerosol chemotherapy (PIPAC) with paclitaxel in patients with platinum-resistant recurrent ovarian cancer and peritoneal carcinomatosis.
详细描述
The Study Design is an interventional, non-randomized, sequential Phase 1/2a trial, where patients with platinum-resistant recurrent ovarian cancer(PROC) and radiologically confirmed peritoneal carcinomatosis will be enrolled.
All patients included in this study will receive PIPAC, laparoscopic aerosolization of paclitaxel under 12 mmHg pressure at 6-week intervals (up to 9 cycles) for treating PROC with peritoneal metastasis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 85 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Age: Women aged 19-85 years.
- •Diagnosis: Histologically confirmed ovarian, fallopian tube, or peritoneal cancer.
- •Platinum Status:
- •Refractory: Disease progression during platinum-based chemotherapy.
- •Resistant: Progression within 6 months (24 weeks) post-platinum therapy.
- •Prior Therapies: ≥2 prior intravenous chemotherapies (may include paclitaxel).
- •Treatment Options: Unresponsive to/ineligible for standard therapies (e.g., intolerance, hypersensitivity) and ineligible for surgical resection.
- •Measurable Disease: ≥1 measurable/evaluable peritoneal lesion per RECIST 1.
- •Metastasis: ≤1 asymptomatic distant metastasis (excluding retroperitoneal lymph nodes, pleural effusion, localized skin metastases).
- •Imaging Confirmation: Peritoneal carcinomatosis confirmed by PET-CT/CT.
- •Performance Status: ECOG 0-
- •Pregnancy/Contraception:
- •Non-pregnant/non-lactating.
- •Contraception: Effective methods (IUD, sterilization) for 6 months post-PIPAC (childbearing potential only).
- •Organ Function:
- •Bone Marrow: ANC >1,500/mm³, platelets >100,000/mm³, hemoglobin >8.0 g/dL.
- •Liver: Bilirubin ≤1.5×ULN, AST/ALT ≤1.5×ULN.
- •Kidney: Creatinine ≤1.5×ULN, creatinine clearance >60 mL/min.
- •Lungs: FVC/FEV1 ≥70% predicted.
- •Coagulation: INR ≤1.5, aPTT ≤1.5×ULN.
- •Consent: Signed informed consent.
排除标准
- •≥2 distant metastases (excluding retroperitoneal lymph nodes, pleural effusion, and localized skin metastases).
- •Contraindications to paclitaxel per approved domestic labeling.
- •Hypersensitivity history to paclitaxel or PIPAC devices.
- •Uncontrolled comorbidities per investigator judgment:
- •NYHA Class ≥II heart failure
- •Clinically significant cardiovascular disease (e.g., arrhythmia, myocardial infarction)
- •Immunosuppressive conditions (AIDS, autoimmune diseases, immunosuppressive therapy)
- •Active HBV/HCV infection
- •Uncontrolled hypertension (systolic >160 mmHg or diastolic >100 mmHg)
- •Uncontrolled diabetes (HbA1c >8%)
- •Radiographic/clinical bowel obstruction.
- •IV chemotherapy within 4 weeks prior to Cycle 1 PIPAC.
- •Life expectancy <3 months.
- •Prior PIPAC therapy.
- •Medically unfit for general anesthesia or laparoscopic surgery.
- •Refusal of contraception:
- •- Medically acceptable methods:
- •Intrauterine device (failure rate <1%)
- •Surgical sterilization (tubal ligation, hysterectomy, vasectomy; failure rate <0.5%).
- •Participation in another clinical trial within 1 month of screening.
- •Other exclusionary factors per investigator discretion.
研究组 & 干预措施
PIPAC-OVPAC group
干预措施: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) using paclitaxel (Drug)
结局指标
主要结局
Dose limiting toxicities
时间窗: Till 6 weeks after the first PIPAC in phase 1 study
Dose limiting toxicities
Maximum tolerated dose
时间窗: During phase 1 study (up to 6 weeks)
We consider dose escalation if 3 consecutive DLTs do not occur, or less than 1 in 6 DLTs occur, per standard 3+3 design. If DLT occurs in 2 or more of 6, the lower dose is considered the MTD if 1 or fewer DLTs are identified. In addition, the highest dose (140 mg/m2) is considered the MTD when 3 to 0 DLTs or 6 to 1 DLTs are identified at the highest dose. On the other hand, if the initial dose (20 mg/m2) is reduced to 10 mg/m2 to account for DLT, it is considered the MTD if no more than 1 in 6 develop DLT at that reduced dose.
Recommended Phase 2 Dose
时间窗: During phase 1 study
Recommended Phase 2 Dose determined by dose limiting toxicities
Disease control rate
时间窗: During phase 2 study
Disease control rate at the 9-week time point
次要结局
- Peritoneal Regression Grading Score(During phase 1 and 2a studies)
- The Risk of Ovarian Malignancy Algorithm (ROMA) score(Assessed at every visit during the study period)
- Safety evaluation(During phase 1 and 2a studies)
- Maximum concentration (Cmax)(During phase 1 study)
- Time at which Cmax is observed (Tmax)(During phase 1 study)
- Area under the curve (AUC)(During phase 1 study)
- Disease control rate(During phase 1 study)
- Peritoneal cancer index(During phase 1 and 2a studies)
- Changes in ascites volume(During phase 1 and 2a studies)
- EORTC QLQ-C30 questionnaire(During phase 1 and 2a studies)
- Progression-free survival(During phase 1 and 2a studies)
- Overall survival(During phase 1 and 2a studies)
- CA-125(Assessed at every visit during the study period)
- EORTC QLQ-OV28 questionnaire measured during the study(During phase 1 and 2a studies)
- human epididymis protein 4 (HE4)(Assessed at every visit during the study period)
研究者
Hee Seung Kim
Professor
Seoul National University Hospital