About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Parallel
Treatments tested in this trial
Bevacizumab
Biological/VaccineGiven IV
Biopsy Procedure
Procedure/SurgeryUndergo biopsy
Biospecimen Collection
Procedure/SurgeryUndergo collection of blood, urine, and ascites
Computed Tomography
Procedure/SurgeryUndergo CT
Fluorouracil
DrugGiven IV
Irinotecan Hydrochloride
DrugGiven IV
Leucovorin Calcium
DrugGiven IV
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Mitomycin
DrugGiven via PIPAC
Questionnaire Administration
Other interventionAncillary studies
Treatment groups
Trial outcomes
Primary outcomes
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.
Secondary outcomes
Progression-free survival (PFS)
Progression is as assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 via contrast-enhanced computed tomography scan. CIs for the true success proportion will be calculated according to the approach of Clopper and Pearson.
Win ratio
Will be based on OS events being more clinically meaningful than PFS events.
Objective response rate
Will be measured by RECIST 1.1, Peritoneal Regression Grading Score (PRGS), Peritoneal Carcinomatosis Index (PCI) on diagnostic laparoscopy, and biochemical response with serum tumor marker. For RECIST criteria, efficacy can be defined as the percentage of evaluable patients who have achieved complete response (CR), partial response (PR), or stable disease (SD). For PCI, efficacy can be defined as the percentage of evaluable patients who have achieved CR, PR, or SD. For PRGS, efficacy can be defined as the percentage of evaluable patients who have achieved a decrease in average PRGS over successive biopsies. The proportion of successes will be estimated by the number of successes divided by the total number of patients initiating therapy. Confidence intervals for the true success proportion will be calculated according to the approach of Clopper and Pearson.
Incidence of post-operative surgical complications
Will be measured by Clavien-Dindo classification 4 weeks after each PIPAC. Results will be strictly descriptive in nature.
Sponsors and contacts
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City of Hope Medical Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator