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

Starting soon · Phase 3

Conditions studied: 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

In brief

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.

Key facts

Study ID

NCT07271355

Run by

City of Hope Medical Center

People needed

129

Starts

2026-07-01

Expected to finish

2031-02-28

Last updated by the study team

2025-12-09

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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)
• Hemoglobin ≥ 8 g/dL (To be performed within 28 days prior to Day 1 of protocol therapy)
• Serum albumin ≥ 2.8 g/dL (To be performed within 28 days prior to Day 1 of protocol therapy)
• Total bilirubin ≤ 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease, then direct bilirubin < 1.5 mg/dL) (To be performed within 28 days prior to Day 1 of protocol therapy)
• Aspartate aminotransferase (AST) ≤ 5 x ULN (To be performed within 28 days prior to Day 1 of protocol therapy)
• Alanine aminotransferase (ALT) ≤ 5 x ULN (To be performed within 28 days prior to Day 1 of protocol therapy)
• Calculated creatinine clearance of ≥ 45 mL/min per 24-hour urine test or the Cockcroft-Gault formula (To be performed within 28 days prior to Day 1 of protocol therapy)
• Women of childbearing potential (WOCBP): Negative urine or serum pregnancy test (To be performed within 28 days prior to Day 1 of protocol therapy)
• If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Agreement by females and males of childbearing potential to use an effective method of birth control (e.g. licensed hormonal/barrier methods or surgery intended to prevent pregnancy [or with a side effect of pregnancy prevention]) or abstain from heterosexual activity for the course of the study through at least 14 months after the last dose of protocol therapy
• Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)

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)
• Ascites (> 2L drained per month)
• Adhesions involving > 50% of abdominal cavity on diagnostic laparoscopy
• Life expectancy < 6 months
• Treatment with therapeutic oral or IV antibiotics within 14 days prior to Day 1 Cycle 1 of treatment
• Patients receiving prophylactic antibiotics are eligible, provided the signs of active infection have resolved
• Any prior malignancy except adequately treated basal or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for two years
• History of allergic or hypersensitivity reactions attributed to compounds of similar chemical or biologic composition to study agents (platinum-based compounds, etc.)
• History of allogeneic organ transplantation or other active primary immunodeficiency
• Active and uncontrolled infection, including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), or human immunodeficiency virus (positive HIV 1/2 antibodies)
• Clinically significant uncontrolled illness, including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active interstitial lung disease (ILD), serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase the risk of incurring AEs, or compromise the ability of the patient to give written informed consent

Where it is running

• CTCA at Western Regional Medical Center — Goodyear, Arizona, United States
• City of Hope Comprehensive Cancer Center — Duarte, California, United States
• City of Hope at Irvine Lennar — Irvine, California, United States
• City of Hope Atlanta Cancer Center — Newnan, Georgia, United States
• City of Hope at Chicago — Zion, Illinois, United States

Full record on ClinicalTrials.gov

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