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

Phase 2Not Yet RecruitingNCT07273396

Seoul National University Hospital53 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Ovarian Neoplasms Peritoneal Neoplasms

Interventions

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) using paclitaxelDRUG

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.

Eligibility

Sex: FEMALEMin age: 19 YearsMax age: 85 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Dose limiting toxicities

Time frame: Till 6 weeks after the first PIPAC in phase 1 study

Maximum tolerated dose

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.

Time frame: During phase 1 study (up to 6 weeks)

Recommended Phase 2 Dose

Recommended Phase 2 Dose determined by dose limiting toxicities

Time frame: During phase 1 study

Disease control rate

Disease control rate at the 9-week time point

Time frame: During phase 2 study

Secondary Outcomes

Maximum concentration (Cmax)

Cmax on pharmacokinetic evaluation of paclitaxel administered via pressurized intraperitoneal aerosol chemotherapy

Time frame: During phase 1 study

Time at which Cmax is observed (Tmax)

Tmax on pharmacokinetic evaluation of paclitaxel administered via pressurized intraperitoneal aerosol chemotherapy

Time frame: During phase 1 study

Area under the curve (AUC)

AUC on pharmacokinetic evaluation of paclitaxel administered via pressurized intraperitoneal aerosol chemotherapy

Central Contacts

Hee Seung Kim, MD, PhD

CONTACT

82-02-2072-4863 bboddi0311@snu.ac.kr

Data from ClinicalTrials.gov

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