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

Official title

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)

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.

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.

Interventions

• 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) 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

Primary outcome measures

• Dose limiting toxicities [Time frame: Till 6 weeks after the first PIPAC in phase 1 study]
• Maximum tolerated dose [Time frame: During phase 1 study (up to 6 weeks)]
• Recommended Phase 2 Dose [Time frame: During phase 1 study]
• Disease control rate [Time frame: During phase 2 study]

Secondary outcome measures (12)

• Maximum concentration (Cmax) [Time frame: During phase 1 study]
• Time at which Cmax is observed (Tmax) [Time frame: During phase 1 study]
• Area under the curve (AUC) [Time frame: During phase 1 study]
• Disease control rate [Time frame: During phase 1 study]
• Progression-free survival [Time frame: During phase 1 and 2a studies]
• Overall survival [Time frame: During phase 1 and 2a studies]
• Peritoneal cancer index [Time frame: During phase 1 and 2a studies]
• Peritoneal Regression Grading Score [Time frame: During phase 1 and 2a studies]
• Changes in ascites volume [Time frame: During phase 1 and 2a studies]
• CA-125 [Time frame: Assessed at every visit during the study period]
• human epididymis protein 4 (HE4) [Time frame: Assessed at every visit during the study period]
• The Risk of Ovarian Malignancy Algorithm (ROMA) score [Time frame: Assessed at every visit during the study period]

Eligibility criteria

Inclusion criteria

• 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 1.1.
• 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 0-2.
• 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.

Exclusion criteria

• ≥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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07273396 · PIPAC-OVPAC-1/2a

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗