Safety of Pressurized Intraperitoneal Aerosolized Chemotherapy (PIPAC) in Biliary Tract Cancer Patients With Peritoneal Metastases

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Trial Details

Sponsor: City of Hope Medical Center (other)

Phase: 1

Start date: Sept. 19, 2022

Planned enrollment: 12

Trial ID: NCT05285358
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More trial details at ClinicalTrials.gov More info

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Goal: Assess the safety and tolerability of adding pressurized intraperitoneal aerosolized chemotherapy (PIPAC) delivery of nab-paclitaxel to standard systemic gemcitabine and cisplatin in biliary tract cancer with peritoneal metastases, and generate preliminary signals of efficacy and feasibility.

Patients: Adults (≥18 years) with histologically or cytologically confirmed intrahepatic or extrahepatic cholangiocarcinoma or gallbladder cancer, ECOG 0–1, radiologically or laparoscopically evident peritoneal metastases, adequate organ function, and no prior systemic therapy for advanced disease. Key exclusions include extensive liver involvement (≥50%), CNS metastases, significant neuropathy (≥grade 2), active infections requiring recent antibiotics, and recent adjuvant therapy (<6 months).

Design: Single-arm, open-label, phase 1 safety study with descriptive secondary efficacy and feasibility endpoints; planned enrollment 12. No randomization or blinding. Follow-up at 4 weeks post-treatment and then every 3 months.

Treatments: Systemic gemcitabine IV and cisplatin IV on days 1 and 8 of 21-day cycles, with intraperitoneal nab-paclitaxel delivered as PIPAC on day 3 of cycles 1, 3, and 5; up to 8 cycles unless progression or unacceptable toxicity. Nab-paclitaxel (albumin-bound paclitaxel) is a microtubule inhibitor facilitating paclitaxel delivery without solvents; when administered via PIPAC, it is aerosolized under pressure during laparoscopy to enhance peritoneal tissue penetration and distribution while potentially reducing systemic exposure. Clinical results for nab-paclitaxel via PIPAC in biliary tract cancer are not yet established; this trial seeks safety data and pharmacologic rationale rather than efficacy proof.

Outcomes: Primary: Incidence and characterization of treatment-related adverse events by NCI CTCAE v5.0 within the first 6 weeks. Secondary: Efficacy by PCI at laparoscopy, RECIST responses on CT, and PGRS on peritoneal biopsies at each PIPAC; postoperative complications by Clavien-Dindo within 4 weeks after each PIPAC; overall and progression-free survival; quality of life and symptoms by EQ-5D-5L and MDASI; functional status via daily step counts. Exploratory: Tumor subclonal evolution and microenvironment, with immune profiling; pharmacokinetic and pharmacodynamic assessments of intraperitoneal nab-paclitaxel.

Burden on patient: Moderate to high. Patients undergo standard-of-care IV chemotherapy on days 1 and 8 each cycle plus three scheduled laparoscopic procedures for PIPAC (cycles 1, 3, and 5), each requiring anesthesia, hospital visits, and peritoneal biopsies. Additional assessments include serial CT imaging, repeated laboratory monitoring, adverse event evaluations, and quality-of-life questionnaires at multiple time points. Functional monitoring with a wrist pedometer is low burden, but exploratory PK/PD sampling and tissue acquisition during laparoscopy add procedural and travel demands beyond standard gemcitabine/cisplatin care.

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City of Hope Medical Center

Duarte, California, 91010, United States

[email protected] / 626-471-9200

Status: Recruiting

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