Pressurized Intraperitoneal Chemotherapy for Colorectal Cancer

Not yet recruiting at 4 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: City of Hope Medical Center

Must not be taking: CYP3A4 inducers/inhibitors, others

Disqualifiers: Irinotecan progression, Second-line chemotherapy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 2

Duration: 18 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of delivering chemotherapy for individuals with appendix or colorectal cancer that has spread within the abdomen and cannot be surgically removed. It compares a technique called PIPAC, which sprays chemotherapy directly into the abdomen, with standard chemotherapy administered intravenously. The goal is to determine if this new method enhances the effectiveness of chemotherapy. Individuals with appendix or colorectal cancer that has spread in the abdomen, who have not responded to standard treatments, may be suitable candidates for this trial. As a Phase 3 trial, it represents the final step before FDA approval, providing patients an opportunity to access potentially groundbreaking treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that pressurized intraperitoneal aerosolized chemotherapy (PIPAC) using mitomycin is generally well-tolerated. Research indicates a very low risk of death related to this treatment, at just 0.1%, making it quite safe for most patients. One study found that chemotherapy with PIPAC and mitomycin is both feasible and safe for treating advanced abdominal cancers.

The FOLFIRI regimen, a standard chemotherapy treatment, includes leucovorin, fluorouracil, and irinotecan. It is often combined with bevacizumab, a drug that inhibits tumor growth by cutting off their blood supply. These treatments are widely used and approved for colorectal cancer. Many patients tolerate these drugs well, although side effects can occur, as with any chemotherapy. Discuss any concerns with the healthcare team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for colorectal cancer?

Researchers are excited about the treatment featuring pressurized intraperitoneal chemotherapy (PIPAC) with mitomycin for colorectal cancer because it delivers chemotherapy directly to the cancerous area in the abdomen, potentially increasing its effectiveness while minimizing systemic side effects. Unlike standard treatments such as FOLFIRI with bevacizumab, which are administered intravenously and affect the entire body, PIPAC targets the tumor site more precisely. This targeted approach could lead to better outcomes and fewer side effects, making it a promising advancement in colorectal cancer treatment.

What evidence suggests that this trial's treatments could be effective for colorectal cancer?

Research has shown that using mitomycin in a method called pressurized intraperitoneal aerosol chemotherapy (PIPAC) appears promising for treating colorectal cancer that has spread to the abdominal lining. In this trial, one group of participants will receive mitomycin via PIPAC along with FOLFIRI and bevacizumab. Some studies reported that about 21% of patients experienced a complete response, meaning their cancer was no longer detectable after treatment. On average, these patients lived for about 15 months, with their cancer remaining under control for about 6 months. This method delivers chemotherapy directly to the cancerous area, potentially increasing its effectiveness. The use of PIPAC with mitomycin is still under investigation, but early results suggest it could be a beneficial option for those with advanced colorectal cancer. ^{3 6 7 8 9}

Who Is on the Research Team?

Mustafa Raoof

Principal Investigator

City of Hope Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with appendix or colorectal cancer that can't be surgically removed and has spread to the lining of the abdomen. Participants should not have had prior chemotherapy for metastatic disease and must be able to undergo medical imaging and biopsies.

Inclusion Criteria

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

Exclusion Criteria

Various medical conditions and history that contraindicate participation in the study

CROSS-OVER ARM EXCLUSION: Various exclusions specific to the cross-over arm

I have received second-line chemotherapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients receive mitomycin via PIPAC and FOLFIRI regimen, with optional bevacizumab, in cycles

18 weeks

Multiple visits (in-person) for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Long-term follow-up

Participants are followed up every 8-12 weeks until death

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Mitomycin

Trial Overview The trial tests a new method called PIPAC with mitomycin, delivered as an aerosol during laparoscopy, against standard intravenous chemotherapy (FOLFIRI regimen) plus bevacizumab. It aims to see if PIPAC leads to better outcomes in treating peritoneal metastases from colorectal or appendix cancer.

How Is the Trial Designed?

Group I: Arm I (mitomycin PIPAC, FOLFIRI, bevacizumab) Experimental Treatment 10 Interventions

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.

Group II: Arm II (FOLFIRI, bevacizumab) Active Control 9 Interventions

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.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9742457/

Multicenter dose-escalation Phase I trial of mitomycin C ... Another retrospective study of 74 PIPAC–oxaliplatin procedures in 24 patients with CRC-PM demonstrated 21% had complete response and a median ...

2. jamanetwork.com jamanetwork.com/journals/jamasurgery/fullarticle/2804110

Efficacy and Safety of Intraoperative Hyperthermic ... This phase 3 randomized clinical trial assesses locoregional control rates after hyperthermic intraperitoneal chemotherapy with mitomycin C ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1533002824001154

Oncological Outcomes From Cytoreductive Surgery and ... This study evaluates outcomes for CRPM patients undergoing CRS+HIPEC with Oxaliplatin (Ox) 368mg/m 2 (30 min), versus Mitomycin C (MMC) 35mg/m 2 (90min).

4. link.springer.com link.springer.com/article/10.1007/s44178-025-00194-0

a meta-analysis of feasibility, efficacy, and safety The median survival time observed was 15.15 months, while median progression-free survival (PFS) was 6.08 months. However, most of the patients ...

5. vivo.weill.cornell.edu vivo.weill.cornell.edu/display/pubid36560966

Multicenter dose-escalation Phase I trial of mitomycin C ... We aim to conduct a dose-escalation trial of mitomycin C (MMC)-PIPAC combined with systemic chemotherapy (FOLFIRI) in patients with PM from ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11544814/

Pressurized Intraperitoneal Aerosol Chemotherapy for ... Only four studies reported a decrease in the average PCI score for 50% of the patients. Median overall survival ranged from 8 to 37.8 months.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT07271355

Pressurized Intraperitoneal Aerosolized Chemotherapy ... This phase III trial studies how well pressurized intraperitoneal aerosolized chemotherapy (PIPAC) with mitomycin works versus (vs) standard ...

8. cancernetwork.com cancernetwork.com/view/pipac-mmc-plus-folfiri-shows-feasibility-safety-in-peritoneal-metastases

PIPAC-MMC Plus FOLFIRI Shows Feasibility, Safety in ... Of 19 patients treated with chemotherapy plus PIPAC-MMC across 3 dose levels, 1 (5.3%) attained a complete response, 2 (10.5%) attained a ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12345692/

Advances in Bidirectional Therapy for Peritoneal Metastases Among studies reporting survival outcomes, the median overall survival (OS) from the first PIPAC was 10.5 months, while the median OS from the ...