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

NCT ID: NCT07273396

Last Updated: 2025-12-09

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-01
• Study Completion Date: 2030-08-31

Brief Summary

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.

Detailed Description

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.

Conditions

Ovarian Neoplasms; Peritoneal Neoplasms

Study Design

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

Study Groups

PIPAC-OVPAC group

Group Type: EXPERIMENTAL

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) using paclitaxel

Intervention Type: DRUG

All patients enrolled in this study receive PIPAC using paclitaxel under 12 mmHg at 6 weeks intervals (up to 9 cycles)

1. Phase 1 Design

1. Dose Escalation: Standard 3+3 design across 5 paclitaxel cohorts (20 → 40 → 67 → 100 → 140 mg/m²) using modified Fibonacci increments (100%, 67%, 50%, 40%).

2. Maximum tolerated dose(MTD) Determination

• If ≥2/6 patients in cohort χ experience dose limiting toxicities(DLTs; Grade ≥3 toxicity per CTCAE v5.0, excluding manageable pain) and ≤1/6 in cohort χ-1, MTD = χ-1.
• If no DLTs at 140 mg/m², Phase 1 concludes.

3. Dose Reduction

• DLTs in 20 mg/m² trigger de-escalation to 10 mg/m².
• If ≤1/6 DLTs in 10 mg/m² → RP2D; ≥2/6 DLTs → trial termination.

2. Phase 2 Design : Evaluates efficacy/safety of PIPAC at the RP2D in 23 patients, adjusting for 5-17% laparoscopic access failure.

Interventions

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) using paclitaxel

All patients enrolled in this study receive PIPAC using paclitaxel under 12 mmHg at 6 weeks intervals (up to 9 cycles)

1. Phase 1 Design

1. Dose Escalation: Standard 3+3 design across 5 paclitaxel cohorts (20 → 40 → 67 → 100 → 140 mg/m²) using modified Fibonacci increments (100%, 67%, 50%, 40%).

2. Maximum tolerated dose(MTD) Determination

• If ≥2/6 patients in cohort χ experience dose limiting toxicities(DLTs; Grade ≥3 toxicity per CTCAE v5.0, excluding manageable pain) and ≤1/6 in cohort χ-1, MTD = χ-1.
• If no DLTs at 140 mg/m², Phase 1 concludes.

3. Dose Reduction

• DLTs in 20 mg/m² trigger de-escalation to 10 mg/m².
• If ≤1/6 DLTs in 10 mg/m² → RP2D; ≥2/6 DLTs → trial termination.

2. Phase 2 Design : Evaluates efficacy/safety of PIPAC at the RP2D in 23 patients, adjusting for 5-17% laparoscopic access failure.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Seoul National University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Hee Seung Kim

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hee Seung Kim, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Seoul National University College of Medicine

Central Contacts

Hee Seung Kim, MD, PhD

Role: CONTACT

bboddi0311@snu.ac.kr

82-02-2072-4863

Other Identifiers

PIPAC-OVPAC-1/2a

Identifier Type: -

Identifier Source: org_study_id