Tolerance, Safety, Efficacy, and Pharmacokinetics of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) Using Paclitaxel for Platinum-resistant Recurrent Ovarian Cancer

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)

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.

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.

Inclusion Criteria:

1. Age: Women aged 19-85 years.

2. Diagnosis: Histologically confirmed ovarian, fallopian tube, or peritoneal cancer.

3. Platinum Status:

   • Refractory: Disease progression during platinum-based chemotherapy.
   • Resistant: Progression within 6 months (24 weeks) post-platinum therapy.

4. Prior Therapies: ≥2 prior intravenous chemotherapies (may include paclitaxel).

5. Treatment Options: Unresponsive to/ineligible for standard therapies (e.g., intolerance, hypersensitivity) and ineligible for surgical resection.

6. Measurable Disease: ≥1 measurable/evaluable peritoneal lesion per RECIST 1.1.

7. Metastasis: ≤1 asymptomatic distant metastasis (excluding retroperitoneal lymph nodes, pleural effusion, localized skin metastases).

8. Imaging Confirmation: Peritoneal carcinomatosis confirmed by PET-CT/CT.

9. Performance Status: ECOG 0-2.

10. Pregnancy/Contraception:

    • Non-pregnant/non-lactating.
    • Contraception: Effective methods (IUD, sterilization) for 6 months post-PIPAC (childbearing potential only).

11. 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.

12. Consent: Signed informed consent.

Exclusion Criteria:

1. ≥2 distant metastases (excluding retroperitoneal lymph nodes, pleural effusion, and localized skin metastases).

2. Contraindications to paclitaxel per approved domestic labeling.

3. Hypersensitivity history to paclitaxel or PIPAC devices.

4. 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.

5. IV chemotherapy within 4 weeks prior to Cycle 1 PIPAC.

6. Life expectancy <3 months.

7. Prior PIPAC therapy.

8. Medically unfit for general anesthesia or laparoscopic surgery.

9. Refusal of contraception:

   - Medically acceptable methods:

   • Intrauterine device (failure rate <1%)
   • Surgical sterilization (tubal ligation, hysterectomy, vasectomy; failure rate <0.5%).

10. Participation in another clinical trial within 1 month of screening.

11. Other exclusionary factors per investigator discretion.