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Not Yet RecruitingNCT07271355

Pressurized Intraperitoneal Aerosolized Chemotherapy With Mitomycin for the Treatment of Unresectable Appendix or Colorectal Cancer With Peritoneal Metastases, The IMPACT Trial

Investigation of Mitomycin C PIPAC - FOLFIRI Combination for Unresectable Appendiceal or Colorectal Peritoneal Metastases Treatment (IMPACT): A Multicenter, Randomized, Open-Label, Phase 3 Trial

Status
Not Yet Recruiting
Phase
Phase 3
Study type
Interventional
Enrollment
129 (estimated)
Sponsor
City of Hope Medical Center · Academic / Other
Sex
All
Age
18 Years
Healthy volunteers
Not accepted

Summary

This phase III trial studies how well pressurized intraperitoneal aerosolized chemotherapy (PIPAC) with mitomycin works versus (vs) standard chemotherapy (leucovorin calcium, fluorouracil, and irinotecan hydrochloride \[FOLFIRI regimen\] plus bevacizumab) in treating patients with appendix or colorectal cancer that cannot be removed by surgery (unresectable) and has spread from where it first started (primary site) to the abdominal cavity (peritoneal metastases). PIPAC is a new therapeutic approach that is minimally invasive, does not require surgery (laparotomy), and can be frequently repeated. Chemotherapy is delivered as a pressurized mist directly inside the abdominal cavity (peritoneum) during a minimally invasive surgery called a laparoscopy. The pressure helps the chemotherapy absorb into the cancer tissue and spread more evenly. Mitomycin is an antibiotic used as a chemotherapy drug. It stops or slows the growth of cancer cells and other rapidly growing cells by damaging their deoxyribonucleic acid (DNA). Standard chemotherapy drugs, such as those in the FOLFIRI regimen, are given via infusion into a vein (intravenously), and work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Another standard intravenous drug, bevacizumab, is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Giving mitomycin via PIPAC in combination with the standard FOLFIRI regimen, with or without bevacizumab, may work better than standard FOLFIRI plus bevacizumab alone in treating patients with unresectable appendix or colorectal cancer with peritoneal metastases.

Detailed description

PRIMARY OBJECTIVE: I. Evaluate the overall survival of patients treated with mitomycin PIPAC (MMC-PIPAC) in combination with systemic FOLFIRI in comparison to those treated with systemic FOLFIRI/bevacizumab as a 2nd line therapy in patients with appendiceal or colorectal cancer with peritoneal metastases. SECONDARY OBJECTIVES: I. Compare progression-free survival between the two arms. II. Rate of completion of cytoreductive surgery. III. Evaluate the Objective response rate by arm, assessed by: IIIa. Peritoneal Regression Grading Score (PRGS) via histologic assessment of biopsies performed at each PIPAC cycle; IIIb. Laparoscopic Peritoneal Carcinomatosis Index (PCI) reduction; IIIc. Radiographic response by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1; IIId. Tumor marker (CEA) response rate. IV. Patient-reported health state/quality of life and symptoms before treatment, at 6 months and at 1-year, as measured by European Organisation for the Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ30) and EORTC-Colorectal Cancer (CR29) for each arm. EXPLORATORY OBJECTIVES: I. Characterization of sub-clonal and tumor microenvironment evolution in response to therapy with a particular focus on immune and fibroblast subsets in the tumor and immune subsets in peripheral blood. II. Correlating cell free DNA, ribonucleic acid (RNA), proteins and/or metabolites in blood and peritoneal fluid with burden of disease, survival and response to therapy. III. Develop artificial intelligence and machine learning approaches for the characterization of peritoneal metastases by correlating video/photographic imaging features of peritoneal metastases to histologic features. IV. Establish the feasibility of generating patient-derived xenografts, organoids, and cell lines from pre-treated colorectal and appendiceal cancer peritoneal metastases (City of Hope \[COH\] only). V. Characterization of stool and tissue microbiome of patients on the study protocol. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive mitomycin via PIPAC during on day 1 of each cycle. Cycles repeat every 6 weeks for 3 cycles in the absence of disease progression or unacceptable toxicity. Beginning 2 weeks after each mitomycin PIPAC treatment, patients receive FOLFIRI regimen, consisting of irinotecan intravenously (IV) over 90 minutes on day 1 of each cycle, leucovorin IV over 30 minutes on day 1 of each cycle, and fluorouracil IV over 46-48 hours on day 1 of each cycle (i.e., weeks 2, 4, 8, 10, 14, 16, etc). Cycles of FOLFIRI regimen repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after last cycle of mitomycin PIPAC, patients may also receive bevacizumab IV over 30-90 minutes at the discretion of the treating physician. Cycles of bevacizumab repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive FOLFIRI regimen, consisting of irinotecan IV over 90 minutes on day 1 of each cycle, leucovorin IV over 30 minutes on day 1 of each cycle, and fluorouracil IV over 46-48 hours on day 1 of each cycle. Cycles repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after standard laparoscopy, patients also receive bevacizumab IV over 30-90 minutes on day 1 of each cycle. Cycles of bevacizumab repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression may cross-over to Arm I (NOTE: Cross-over patients do not receive FOLFIRI regimen). All patients also undergo computed tomography (CT), collection of blood, ascites, and urine samples, as well as biopsies throughout the study. Patients may also undergo magnetic resonance imaging (MRI) during screening. After completion of study treatment, patients are followed up at 4 weeks and then every 8-12 weeks until death.

Conditions

Interventions

TypeNameDescription
BIOLOGICALBevacizumabGiven IV
PROCEDUREBiopsy ProcedureUndergo biopsy
PROCEDUREBiospecimen CollectionUndergo collection of blood, urine, and ascites
PROCEDUREComputed TomographyUndergo CT
DRUGFluorouracilGiven IV
DRUGIrinotecan HydrochlorideGiven IV
DRUGLeucovorin CalciumGiven IV
PROCEDUREMagnetic Resonance ImagingUndergo MRI
DRUGMitomycinGiven via PIPAC
OTHERQuestionnaire AdministrationAncillary studies

Timeline

Start date
2026-07-01
Primary completion
2031-02-28
Completion
2031-02-28
First posted
2025-12-09
Last updated
2025-12-09

Locations

5 sites across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT07271355. Inclusion in this directory is not an endorsement.