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.

Study Overview

• Status: Not yet recruiting
• Conditions: Ovarian Neoplasms; Peritoneal Neoplasms
• Intervention / Treatment: Drug: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) using paclitaxel

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.

• Study Type: Interventional
• Enrollment (Estimated): 53
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Hee Seung Kim, MD, PhD; Phone Number: 82-02-2072-4863; Email: bboddi0311@snu.ac.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: PIPAC-OVPAC group

Drug: 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); Phase 1 DesignDose Escalation: Standard 3+3 design across 5 paclitaxel cohorts (20 → 40 → 67 → 100 → 140 mg/m²) using modified Fibonacci increments (100%, 67%, 50%, 40%).Maximum tolerated dose(MTD) DeterminationIf ≥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.Dose ReductionDLTs 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.; Phase 2 Design : Evaluates efficacy/safety of PIPAC at the RP2D in 23 patients, adjusting for 5-17% laparoscopic access failure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose limiting toxicities	Dose limiting toxicities	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.	During phase 1 study (up to 6 weeks)
Recommended Phase 2 Dose	Recommended Phase 2 Dose determined by dose limiting toxicities	During phase 1 study
Disease control rate	Disease control rate at the 9-week time point	During phase 2 study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum concentration (Cmax)	Cmax on pharmacokinetic evaluation of paclitaxel administered via pressurized intraperitoneal aerosol chemotherapy	During phase 1 study
Time at which Cmax is observed (Tmax)	Tmax on pharmacokinetic evaluation of paclitaxel administered via pressurized intraperitoneal aerosol chemotherapy	During phase 1 study
Area under the curve (AUC)	AUC on pharmacokinetic evaluation of paclitaxel administered via pressurized intraperitoneal aerosol chemotherapy	During phase 1 study
Disease control rate	Disease control rate at the 9-week time point	During phase 1 study
Progression-free survival	Time from the treatment start of pressurized intraperitoneal aerosol chemotherapy to the identification of progressive disease or the end of the study	During phase 1 and 2a studies
Overall survival	Time from the treatment start of pressurized intraperitoneal aerosol chemotherapy to cancer-related death or the end of the study	During phase 1 and 2a studies
Peritoneal cancer index	Peritoneal cancer index scores identified during pressurized intraperitoneal aerosol chemotherapy, which range from 0 to 39	During phase 1 and 2a studies
Peritoneal Regression Grading Score	Peritoneal Regression Grading Score examined by pathologic review; Peritoneal Regression Grading Score 1, complete response: Peritoneal Regression Grading Score 2, major response: Peritoneal Regression Grading Score 3, minor response; Peritoneal Regression Grading Score 4, no response	During phase 1 and 2a studies
Changes in ascites volume	Changes in ascites volume measured during pressurized intraperitoneal aerosol chemotherapy	During phase 1 and 2a studies
CA-125	Seum CA-125 levels, which are related to disease progression when more than 35 U/ml	Assessed at every visit during the study period
human epididymis protein 4 (HE4)	Serum HE4 levels, which are related to disease progression when more than 140 pmol/L	Assessed at every visit during the study period
The Risk of Ovarian Malignancy Algorithm (ROMA) score	ROMA score using serum CA-125 and HE4 levels, which are related to disease progression when more than 30%	Assessed at every visit during the study period
EORTC QLQ-C30 questionnaire	EORTC QLQ-C30 questionnaires measured during the study. The evaluation range for each item is from 0 to 100.	During phase 1 and 2a studies
EORTC QLQ-OV28 questionnaire measured during the study	EORTC QLQ-OV28 questionnaire measured during the study. The evaluation range for each item is from 0 to 100.	During phase 1 and 2a studies
Safety evaluation	Safety evaluation per CTCAE v5.0, including treatment-related adverse events and surgical complications. The evaluation range for each item is from grade 1 to grade 5.	During phase 1 and 2a studies

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Investigators: Principal Investigator: Hee Seung Kim, MD, PhD, Seoul National University College of Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): April 30, 2030
• Study Completion (Estimated): August 31, 2030

Study Registration Dates

• First Submitted: May 5, 2025
• First Submitted That Met QC Criteria: November 27, 2025
• First Posted (Estimated): December 9, 2025

Study Record Updates

• Last Update Posted (Estimated): December 9, 2025
• Last Update Submitted That Met QC Criteria: November 27, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: paclitaxel; ovarian cancer; platinum-resistant recurrent; Pressurized intraperitoneal aerosol chemotherapy
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Digestive System Neoplasms; Digestive System Diseases; Genital Diseases, Female; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Peritoneal Diseases; Abdominal Neoplasms; Ovarian Neoplasms; Peritoneal Neoplasms
• Other Study ID Numbers: PIPAC-OVPAC-1/2a

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No