NCT06675136

Nab-Paclitaxel PIPAC in Combination With Paclitaxel and Ramucirumab for the Treatment of Stomach Cancer With Peritoneal Metastases

Phase 1 Trial of Nab-Paclitaxel PIPAC (Pressurized Intraperitoneal Aerosolized Chemotherapy) Given in Combination With Second-Line Therapy for Gastric Cancer With Peritoneal Metastases

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial tests the safety, side effects and best dose of nab-paclitaxel pressurized intraperitoneal aerosolized chemotherapy (PIPAC) in combination with second-line chemotherapy, paclitaxel and ramucirumab, and tests how well they work in treating stomach cancer that has spread from where it first started to the tissue that lines the abdominal wall and organs (peritoneal metastases). Paclitaxel is in a class of medications called antimicrotubule agents. It stops tumor cells from growing and dividing and may kill them. Nab-paclitaxel is an albumin-stabilized nanoparticle formulation of paclitaxel which may have fewer side effects and work better than other forms of paclitaxel. PIPAC delivers chemotherapy, such as nab-paclitaxel, that has been turned into a fine mist (aerosolized) at a high pressure directly into the abdominal cavity. Aerosolized chemotherapy delivered directly into the peritoneal space has been shown to deliver higher drug concentrations to the tumor. Ramucirumab is a monoclonal antibody that may prevent the growth of new blood vessels that tumors need to grow. Giving nab-paclitaxel PIPAC in combination with paclitaxel and ramucirumab may be safe, tolerable, and/or effective in treating gastric cancer patients with peritoneal metastases.

Detailed description

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of nab-paclitaxel PIPAC when given in combination with standard-of-care second-line systemic therapy (paclitaxel, ramucirumab). II. To assess the safety and tolerability of nab-paclitaxel PIPAC plus systemic paclitaxel and ramucirumab, and accompanying dose modification plan, by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration. SECONDARY OBJECTIVES: I. To evaluate the anti-tumor activity of nab-paclitaxel when given in combination with standard-of-care second-line systemic therapy (paclitaxel, ramucirumab), as assessed by: Ia. Response Evaluation Criteria in Solid Tumors (RECIST), if available, version 1.1 via computed tomography (CT) scan at baseline and every 8 weeks until disease progression; Ib. Peritoneal Regression Grading Score (PRGS) via biopsy at each PIPAC cycle (both pre-PIPAC and post-PIPAC peritoneal samples will be obtained); Ic. Peritoneal Carcinomatosis Index (PCI) at the time of laparoscopy; and Id. Overall survival (OS) and progression-free survival (PFS) estimates at 6-months, 1-year and 2-years. II. To estimate the PIPAC technical failure rate. III. To characterize and evaluate peritoneal tumor associated complications. IV. To characterize and evaluate post-operative surgical complications by Clavien-Dindo classification evaluated at 30 days after each PIPAC technical failure rate. V. To evaluate patient-reported health state/quality of life and symptoms before treatment and at 6, 12, 18, and 24 weeks/off study, as measured by the European Quality of Life Five Dimension Five Level Scale (EQ-5D-5L) and MD Anderson Symptom Inventory (MDASI). EXPLORATORY OBJECTIVES: I. Characterize the peritoneal tumor and immune tumor microenvironment changes in response to therapy. II. Evaluate the pharmacokinetics of nab-paclitaxel PIPAC. III. Evaluate patients' quality of life during nab-paclitaxel PIPAC plus systemic therapy. OUTLINE: This is a dose-escalation study of nab-paclitaxel PIPAC in combination with paclitaxel and ramucirumab followed by a dose-expansion study. Patients receive nab-paclitaxel PIPAC intraperitoneally (IP) over 40 minutes on day 1 and standard of care (SOC) paclitaxel intravenously (IV) over 60 minutes on days 15, 22, 29, 43, and 50 and ramucirumab IV over 30-60 minutes on days 15, 29 and 43 of each cycle. Cycles repeat every 8 weeks (56 days) for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients may then continue SOC paclitaxel IV on days 1, 8, and 15 and ramucirumab IV on days 1 and 15 of each cycle per physician as deemed appropriate. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, tumor biopsy, and CT or magnetic resonance imaging (MRI) throughout the study. After completion of study treatment, patients are followed up at 4 weeks, then every 3 months for year 1 followed by every 6 months until progression or initiation of a new systemic anti-cancer therapy or death, whichever occurs first.

Conditions

• Clinical Stage IVB Gastric Cancer AJCC v8
• Metastatic Gastric Adenocarcinoma
• Metastatic Malignant Neoplasm in the Peritoneum

Interventions

Type	Name	Description
PROCEDURE	Biopsy	Undergo tumor biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Computed Tomography	Undergo CT
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
OTHER	Medical Device Usage and Evaluation	Given PIPAC
DRUG	Nab-paclitaxel	Given IP
DRUG	Paclitaxel	Given IV
OTHER	Questionnaire Administration	Ancillary studies
BIOLOGICAL	Ramucirumab	Given IV

Timeline

• Start date: 2025-10-29
• Primary completion: 2029-01-14
• Completion: 2029-01-14
• First posted: 2024-11-05
• Last updated: 2025-11-10

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study