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

NCT07271355 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: 24756NCI-2025-08527P30CA033572
• Study Type: interventional
• Target: 129
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Metastatic Appendix Carcinoma; Metastatic Colorectal Carcinoma; Metastatic Malignant Neoplasm in the Peritoneum; Stage IV Appendix Carcinoma AJCC v8; Stage IVC Colorectal Cancer AJCC v8; Unresectable Colorectal Carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  The primary analysis will follow the intention-to-treat principle. OS will be summarized by the Kaplan-Meier method, and a one-sided stratified log-rank test will be used to compare treatment arms, with hazard ratios and 95 percent confidence intervals (CIs) estimated from Cox proportional hazards models.

  From randomization to death from any cause, assessed up to 5 years

Secondary Outcomes (7)

• Progression-free survival (PFS)

  From randomization to time of progression or death, whichever occurs first, assessed up to 5 years

• Win ratio

  Up to 5 years

• Objective response rate

  Up to 5 years

• Incidence of post-operative surgical complications

  Up to 4 weeks after final pressurized intraperitoneal aerosolized chemotherapy (PIPAC)

• Rate of patients who have cytoreductive surgery

  Up to 5 years

Study Arms (2)

Arm I (mitomycin PIPAC, FOLFIRI, bevacizumab)

EXPERIMENTAL

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 IV over 90 minutes, leucovorin IV over 30 minutes, 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. Patients also undergo CT, collection of blood, ascites, and urine samples, as well as biopsies throughout the study. Patients may also undergo MRI during screening.

Biological: Bevacizumab; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Fluorouracil; Drug: Irinotecan Hydrochloride; Drug: Leucovorin Calcium; Procedure: Magnetic Resonance Imaging; Drug: Mitomycin; Other: Questionnaire Administration

Arm II (FOLFIRI, bevacizumab)

ACTIVE COMPARATOR

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). Patients also undergo CT, collection of blood, ascites, and urine samples, as well as biopsies throughout the study. Patients may also undergo MRI during screening.

Biological: Bevacizumab; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Fluorouracil; Drug: Irinotecan Hydrochloride; Drug: Leucovorin Calcium; Procedure: Magnetic Resonance Imaging; Other: Questionnaire Administration

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of blood, urine, and ascites

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm I (mitomycin PIPAC, FOLFIRI, bevacizumab); Arm II (FOLFIRI, bevacizumab)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Arm I (mitomycin PIPAC, FOLFIRI, bevacizumab); Arm II (FOLFIRI, bevacizumab)

Fluorouracil DRUG

Given IV

Also known as: 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-Fu, 5FU, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757

Arm I (mitomycin PIPAC, FOLFIRI, bevacizumab); Arm II (FOLFIRI, bevacizumab)

Irinotecan Hydrochloride DRUG

Given IV

Also known as: Campto, Camptosar, Camptothecin 11, Camptothecin-11, CPT 11, CPT-11, CPT11, Irinomedac, Irinotecan Hydrochloride Trihydrate, Irinotecan Monohydrochloride Trihydrate, U 101440E, U-101440E, U101440E

Arm I (mitomycin PIPAC, FOLFIRI, bevacizumab); Arm II (FOLFIRI, bevacizumab)

Leucovorin Calcium DRUG

Given IV

Also known as: Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate, Calcium Leucovorin, Calfolex, Calinat, Cehafolin, Citofolin, Citrec, Citrovorum Factor, Cromatonbic Folinico, Dalisol, Disintox, Divical, Ecofol, Emovis, Factor, Citrovorum, Flynoken A, Folaren, Folaxin, FOLI-cell, Foliben, Folidan, Folidar, Folinac, Folinate Calcium, folinic acid, Folinic Acid Calcium Salt Pentahydrate, Folinoral, Folinvit, Foliplus, Folix, Imo, Lederfolat, Lederfolin, Leucosar, leucovorin, Rescufolin, Rescuvolin, Tonofolin, Wellcovorin

Arm I (mitomycin PIPAC, FOLFIRI, bevacizumab); Arm II (FOLFIRI, bevacizumab)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Arm I (mitomycin PIPAC, FOLFIRI, bevacizumab); Arm II (FOLFIRI, bevacizumab)

Mitomycin DRUG

Given via PIPAC

Also known as: Ametycine, Jelmyto, MITO, Mito-C, Mito-Medac, Mitocin, Mitocin-C, Mitolem, Mitomycin C, Mitomycin pyelocalyceal, Mitomycin-C, Mitomycin-X, Mitomycine C, Mitosol, Mitozytrex, Mutamycin, Mutamycine, NCI-C04706

Arm I (mitomycin PIPAC, FOLFIRI, bevacizumab)

Questionnaire Administration OTHER

Ancillary studies

Arm I (mitomycin PIPAC, FOLFIRI, bevacizumab); Arm II (FOLFIRI, bevacizumab)

Bevacizumab BIOLOGICAL

Given IV

Also known as: ABP 215, ABP-215, ABP215, Alymsys, Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF Monoclonal Antibody SIBP04, Anti-VEGF rhuMAb, Avastin, Avzivi, Aybintio, BAT 1706, BAT-1706, BAT1706, BAT1706 Biosimilar, Bevacizumab awwb, Bevacizumab Biosimilar ABP 215, Bevacizumab Biosimilar BAT1706, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar CBT 124, Bevacizumab Biosimilar CT-P16, Bevacizumab Biosimilar FKB238, Bevacizumab Biosimilar GB-222, Bevacizumab Biosimilar HD204, Bevacizumab Biosimilar HLX04, Bevacizumab Biosimilar IBI305, Bevacizumab Biosimilar LY01008, Bevacizumab Biosimilar MB02, Bevacizumab Biosimilar MIL60, Bevacizumab Biosimilar Mvasi, Bevacizumab Biosimilar MYL-1402O, Bevacizumab Biosimilar QL 1101, Bevacizumab Biosimilar QL1101, Bevacizumab Biosimilar RPH-001, Bevacizumab Biosimilar SCT501, Bevacizumab Biosimilar Zirabev, Bevacizumab-adcd, Bevacizumab-awwb, Bevacizumab-aybi, Bevacizumab-bvzr, Bevacizumab-equi, Bevacizumab-maly, Bevacizumab-onbe, Bevacizumab-tnjn, BP102, BP102 Biosimilar, CT P16, CT-P16, CTP16, Equidacent, FKB 238, FKB-238, FKB238, HD204, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, MB 02, MB-02, MB02, Mvasi, MYL-1402O, Onbevzi, Oyavas, PF 06439535, PF-06439535, PF06439535, QL1101, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF, SCT501, SIBP 04, SIBP-04, SIBP04, Vegzelma, Zirabev

Arm I (mitomycin PIPAC, FOLFIRI, bevacizumab); Arm II (FOLFIRI, bevacizumab)

Biopsy Procedure PROCEDURE

Undergo biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Arm I (mitomycin PIPAC, FOLFIRI, bevacizumab); Arm II (FOLFIRI, bevacizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Assent, when appropriate, will be obtained per institutional guidelines
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• If unavailable, exceptions may be granted with study principal investigator (PI) approval
• Age: ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Histologically or cytologically confirmed appendiceal or colorectal cancer peritoneal metastases
• No extraperitoneal metastases except lung ≤ 5 lesions with largest ≤ 1cm as identified on CT imaging or MRI. CT scan or MRI to assess measurable disease must have been completed within 28 days prior to registration
• Visible peritoneal metastatic disease on cross-sectional imaging or diagnostic laparoscopy (does not have to be measurable by RECIST (v1.1)
• Completed at least 4 months (8 cycles) of first-line standard-of-care oxaliplatin-based systemic therapy without progression of disease. Or completed less than 4 months of oxaliplatin based therapy due to intolerance and without progressive disease. Or progressed on first-line standard-of-care oxaliplatin-based systemic therapy. Permissible first-line systemic therapies include leucovorin calcium, fluorouracil, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (XELOX) or fluorouracil, leucovorin, oxaliplatin and irinotecan (FOLFOXIRI). Receipt of anti-EGFR, anti-VEGF, or anti-BRAF therapy in the first-line is acceptable. Mismatch repair-deficient patients are permissible if they have progressed on first-line immunotherapy
• Not a candidate for cytoreductive surgery as determined by site investigator
• Fully recovered from the acute toxic effects of prior anti-cancer therapy to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or lower except alopecia, hearing loss, neuropathy, or non-clinically significant laboratory abnormalities
• Complete medical history and physical exam (To be performed within 28 days prior to Day 1 of protocol therapy)
• Absolute neutrophil count (ANC) ≥ 1,500/mcL (To be performed within 28 days prior to Day 1 of protocol therapy)
• Platelets ≥ 100,000/mcL (To be performed within 28 days prior to Day 1 of protocol therapy)

You may not qualify if:

• More than 8 cycles of first line irinotecan therapy
• Progression on irinotecan
• Receipt of any second-line systemic chemotherapy (Note: Sequential administration of FOLFOX followed by FOLFIRI is considered second line therapy. However, FOLFOXIRI followed by FOLFIRI is considered first line as long as no more than 8 cycles of irinotecan are given)
• Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable
• Strong CYP3A4 inducers/inhibitors within 14 days prior to Day 1 of protocol therapy
• Prior peritoneal-directed chemotherapy (Prior cytoreductive surgery is permitted)
• Participation in another clinical study with an investigational product administered in the last 2 months
• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
• Low-grade appendiceal mucinous neoplasm or low-grade appendiceal mucinous adenocarcinoma
• Extraperitoneal metastases (except lung ≤ 5 lesions with largest being ≤ 1cm)
• Any history of bowel obstruction requiring nasogastric tube, percutaneous endoscopic gastrostomy, or need for total parenteral nutrition. Even if the bowel obstruction resolved with conservative measures, the patient would be excluded. The exception is if the bowel obstruction was surgically addressed with ostomy, resection or bypass. This exception should be documented
• Fused mesenteric disease-causing mesenteric shortening and bowel sequestration ("cauliflowering")
• Bulky mesenteric disease where chemotherapy is unlikely to penetrate the tumor
• Contraindication to laparoscopy
• Rapid weight loss (\> 10% in \< 3 months)

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (5)

CTCA at Western Regional Medical Center

Goodyear, Arizona, 85338, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

City of Hope at Irvine Lennar

Irvine, California, 92618, United States

Location

City of Hope Atlanta Cancer Center

Newnan, Georgia, 30265, United States

Location

City of Hope at Chicago

Zion, Illinois, 60099, United States

Location

MeSH Terms

Conditions

Appendiceal Neoplasms; Colorectal Neoplasms

Interventions

Bevacizumab; Immunoglobulin G; Disulfides; Biopsy; Specimen Handling; Fluorouracil; dehydroftorafur; Irinotecan; Leucovorin; Magnetic Resonance Spectroscopy; Mitomycin; Mitozytrex

Condition Hierarchy (Ancestors)

Cecal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Cecal Diseases; Intestinal Diseases; Colonic Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Spectrum Analysis; Chemistry Techniques, Analytical; Mitomycins; Indolequinones; Quinones; Azirines; Indoles

Study Officials

• Mustafa Raoof

  City of Hope Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2025
• First Posted: December 9, 2025
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): February 28, 2031
• Study Completion (Estimated): February 28, 2031
• Last Updated: December 9, 2025

Record last verified: 2025-11

Locations

US (5)