mEPIC for Peritoneal Cancer

Recruiting at 1 trial location

Overseen By Mikael Soucisse, MD, FRCSC

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ciusss de L'Est de l'Île de Montréal

Disqualifiers: Other malignancies, Pregnancy, Allergic to Fluorouracil, others

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

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of administering chemotherapy after surgery for individuals with peritoneal cancer from colorectal or appendicular tumors. The goal is to determine if a shorter, modified chemotherapy schedule is safe and effective compared to the usual method. Participants will receive chemotherapy directly in the abdomen over two days instead of five. Individuals with colorectal or appendicular cancer that has spread to the peritoneum (the lining of the abdomen) and who have been recommended for surgery and chemotherapy might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer care.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What prior data suggests that the mEPIC protocol is safe?

Research shows that mEPIC aims to improve standard chemotherapy by altering the timing and delivery of the drug. This new method uses 5-FU, a drug already employed in cancer treatment. Studies have found that intraperitoneal chemotherapy, like mEPIC, can effectively target tumors while reducing systemic side effects.

Since mEPIC is in the second phase of trials, it has undergone testing in some patients. Safety is monitored closely, though some side effects might still require further understanding. Previous findings suggest it is generally well-tolerated, but monitoring for adverse effects remains important.

Overall, mEPIC seeks to enhance treatment effectiveness and manageability by utilizing the known properties of 5-FU in a novel way. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for peritoneal cancer, which often involve systemic chemotherapy, mEPIC is administered directly into the abdominal cavity. This direct delivery allows the chemotherapy to target cancer cells more precisely and potentially with less systemic toxicity. Researchers are excited about this approach because it combines the benefits of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with an early post-operative treatment, possibly improving the effectiveness and outcomes for patients with appendicular or colorectal cancer with peritoneal carcinomatosis.

What evidence suggests that mEPIC might be an effective treatment for peritoneal cancer?

Research has shown that early post-operative intraperitoneal chemotherapy (EPIC) can be safely administered after surgery to remove abdominal cancer, particularly colorectal and appendicular cancers. A review of studies found that EPIC helps manage these cancers by targeting any remaining cancer cells in the abdomen post-surgery. In this trial, participants will receive a modified version, mEPIC, which aims to enhance these benefits by adjusting the timing and dosage. This modification reduces the treatment duration from five days to two, potentially making it easier for patients while maintaining effectiveness. The goal is to use the well-known cancer drug fluorouracil (5-FU) more efficiently to improve outcomes. ^{6 7 8 9 10}

Who Is on the Research Team?

Mikael Soucisse, MD, FRCSC

Principal Investigator

CIUSSS de l'Est-de-l'Île-de-Montréal - Hôpital Maisonneuve-Rosemont

Are You a Good Fit for This Trial?

Adults with peritoneal tumors from appendiceal or colorectal cancer, who are in good health and have a low ECOG score (0-1), indicating they can perform daily activities without significant restrictions. They must have completed necessary imaging studies, possibly received neoadjuvant therapy, and be able to undergo surgery followed by mEPIC. Exclusions include allergies to Fluorouracil, other cancers, conditions preventing IP therapy, pregnancy, hemodynamic/respiratory compromise post-surgery.

Inclusion Criteria

Hematology: Absolute neutrophil count (ANC) ≥ 1,500/ μL; Platelets > 75,000/ μL

My surgery is scheduled 4-6 weeks after my last treatment or after joining if I didn't need prior treatment.

My cancer started in the appendix or colon and has spread to the lining of my abdomen.

Exclusion Criteria

I have had surgery to remove as much of the cancer as possible.

Known allergic reaction or major toxicity to Fluorouracil

I do not have uncontrolled bleeding disorders or low blood platelet or white cell counts.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cytoreductive Surgery and HIPEC

Participants undergo cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy

1 day

Treatment (mEPIC)

Participants receive modified early post-operative intraperitoneal chemotherapy (mEPIC) on post-operative days 1 and 2

2 days

In-hospital treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Modified early post-operative intraperitoneal chemotherapy (mEPIC)

Trial Overview The trial is testing the feasibility of a modified chemotherapy regimen called mEPIC after cytoreductive surgery and HIPEC for patients with peritoneal carcinomatosis from colorectal or appendicular tumors. It aims to simplify treatment by reducing it to two days using fluorouracil bolus plus infusion based on De Gramont regimen.

How Is the Trial Designed?

Group I: mEPIC Experimental Treatment 1 Intervention

Adults (male and female) with a diagnosis of appendicular or colorectal cancer with peritoneal carcinomatosis will undergo mEPIC on post-operative days 1 and 2 following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Modified early post-operative intraperitoneal chemotherapy (mEPIC) is already approved in Canada for the following indications:

Approved in Canada as mEPIC for:

• Peritoneal carcinomatosis from colorectal and appendicular neoplasms

Who Is Running the Clinical Trial?

Ciusss de L'Est de l'Île de Montréal

Lead Sponsor

Trials

81

Recruited

6,400+

Maisonneuve-Rosemont Hospital

Collaborator

Trials

102

Recruited

38,300+

Published Research Related to This Trial

In a study of 921 patients with mucinous appendiceal carcinoma, both hyperthermic intraperitoneal chemotherapy (HIPEC) and early post-operative intraperitoneal chemotherapy (EPIC) showed similar rates of serious complications and long-term survival outcomes.

Although HIPEC had a higher readmission rate compared to EPIC (21.2% vs. 8.8%), neither treatment method was found to significantly impact overall survival or recurrence-free survival, suggesting both are viable options for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of HIPEC vs. EPIC for the treatment of mucinous appendiceal carcinoma: a study from the US HIPEC collaborative. Leiting, JL., Day, CN., Harmsen, WS., et al.[2021]

In a study of 390 patients with peritoneal metastases, combining hyperthermic intraperitoneal chemotherapy (HIPEC) with early postoperative intraperitoneal chemotherapy (EPIC) resulted in a longer hospital stay (30 days vs. 24 days) compared to HIPEC alone, indicating a potential increase in recovery time.

Despite the longer hospital stay, there was no significant increase in postoperative morbidity, reoperation rates, or readmission rates, suggesting that HIPEC+EPIC may be safe in terms of these outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Morbidity following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal metastases with or without early postoperative intraperitoneal chemotherapy: A propensity score matched study. Dranichnikov, P., Graf, W., Cashin, PH.[2022]

In a study of 262 patients undergoing cytoreduction for peritoneal carcinomatosis, the combination of hyperthermic intraperitoneal chemotherapy (HIPEC) and early postoperative intraperitoneal chemotherapy (EPIC) showed improved recurrence-free survival (RFS) in colorectal peritoneal carcinomatosis, with a median RFS of 33 months compared to 19 months for HIPEC alone.

For patients with pseudomyxoma peritonei, both HIPEC and EPIC regimens resulted in a 5-year survival rate of 86%, indicating that while the regimen did not affect recurrence-free survival, it may still provide significant survival benefits without increasing perioperative risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative analysis of perioperative intraperitoneal chemotherapy regimen in appendiceal and colorectal peritoneal carcinomatosis. Chua, TC., Liauw, W., Zhao, J., et al.[2022]

In a 25-year study involving 1564 patients undergoing cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy for appendiceal neoplasms, early postoperative intraperitoneal chemotherapy (EPIC) was found to be safely administered, particularly in younger patients and those with complete cytoreduction.

Despite longer hospital stays for patients receiving EPIC, the incidence of major postoperative complications was lower, suggesting that EPIC may be beneficial in carefully selected cases, although further randomized trials are necessary to confirm its impact on long-term survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early postoperative intraperitoneal chemotherapy (EPIC) following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in 632 patients with pseudomyxoma peritonei of appendiceal origin: A single institution experience. Fung, X., Li, IC., Chandrakumaran, K., et al.[2022]

In a study of 206 patients with resectable appendiceal peritoneal metastases, early post-operative intraperitoneal chemotherapy (EPIC) did not improve overall survival or recurrence-free survival compared to those who did not receive EPIC, particularly in patients with low-grade tumors.

Patients receiving EPIC experienced longer hospital and ICU stays, and those with high-grade tumors had significantly worse overall survival when treated with EPIC, suggesting that EPIC may not be beneficial and could lead to increased healthcare resource use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with or without early post-operative intraperitoneal chemotherapy for appendix neoplasms with peritoneal metastases: A propensity score analysis. Soucisse, ML., Fisher, O., Liauw, W., et al.[2021]

In a study of 250 patients with low-grade appendiceal mucinous neoplasms (LAMNs) and pseudomyxoma peritonei (PMP), the combination of hyperthermic intraperitoneal chemotherapy (HIPEC) and early postoperative intraperitoneal chemotherapy (EPIC) was associated with significantly better survival outcomes without increasing postoperative complications.

The study found no significant differences in hospital mortality or major morbidity rates between patients receiving HIPEC alone and those receiving HIPEC + EPIC, suggesting that EPIC can be safely integrated into treatment protocols for LAMNs with PMP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Postoperative Intraperitoneal Chemotherapy for Low-Grade Appendiceal Mucinous Neoplasms with Pseudomyxoma Peritonei: Is it Beneficial? Huang, Y., Alzahrani, NA., Liauw, W., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6812220/

Early postoperative intraperitoneal chemotherapy for lower ... The present study is a systematic review to evaluate the role of EPIC after CRS + HIPEC for appendiceal and colorectal cancers with PC.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0748798322000750

Early postoperative intraperitoneal chemotherapy (EPIC) ... EPIC can be administered safely following CRS and HIPEC for PMP of appendix origin when used in carefully selected patients in a high-volume centre.

3. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT05913674?keyword=%22Neoplasms%2C%20Colorectal%22

San Mateo Clinical Trial Technical Feasibility of Modified ... Our phase II trial proposes a modified schedule of EPIC (mEPIC) designed to maximize therapeutic advantages and reduce logistical barriers. This modified EPIC ( ...

4. ctv.veeva.com ctv.veeva.com/study/technical-feasibility-of-modified-early-post-operative-intraperitoneal-chemotherapy-mepic

Technical Feasibility of Modified Early Post-Operative ... The primary objective of this study is to confirm the feasibility of mEPIC by evaluating its completion rate compared to the one of historical ...

5. jgo.amegroups.org jgo.amegroups.org/article/view/5503/5760

a review of hyperthermic intraperitoneal chemotherapy and ... This review details chemotherapeutic agent selection and modality of treatment for peritoneal-based malignancies.

6. omicsdi.org omicsdi.org/dataset/ecrin-mdr-crc/64145

Technical Feasibility of Modified Early Post-Operative ... The primary objective of this study is to confirm the feasibility of mEPIC by evaluating its completion rate compared to the one of historical standard early ...

7. careacross.com careacross.com/clinical-trials/trial/NCT05913674

Technical Feasibility of Modified Early PostOperative ... The primary objective of this study is to confirm the feasibility of mEPIC by evaluating its completion rate compared to the one of historical standard early ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4754301/

Chemotherapy for intraperitoneal use: a review of ... The role of intraperitoneal chemotherapy is to maximize tumor penetration and optimize cell death while minimizing systemic toxicity. Hyperthermic ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT02040142

NCT02040142 | HIPEC for Peritoneal Carcinomatosis This is a clinical study investigating the new treatment of surgery combined with intraperitoneal mitomycin-C for patients with gastrointestinal cancer that ...

10. withpower.com withpower.com/trial/mepic-for-peritoneal-cancer-ddaba

mEPIC for Peritoneal Cancer The primary objective of this study is to confirm the feasibility of mEPIC by evaluating its completion rate compared to the one of historical standard early ...