mEPIC for Peritoneal Cancer

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

Trial Summary

What is the purpose of this trial?

The goal of this prospective phase II unicentric Canadian clinical trial is to clarify the feasibility of modified early post-operative intraperitoneal chemotherapy (mEPIC) following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in the clinical context of peritoneal carcinomatosis from colorectal and appendicular neoplasms. 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 post-operative intraperitoneal chemotherapy (EPIC) cohorts. The secondary objectives of the study are to evaluate the safety of the mEPIC protocol by monitoring adverse events arising during the protocol and to assess logistical implementation barriers for the nursing and Oncology pharmacy teams, respectively. Participants will undergo a modified schedule of EPIC (mEPIC) designed to maximize therapeutic benefit by exploiting the known pharmacokinetics and pharmacodynamics properties of fluorouracil (5-FU) while limiting the logistical issues of the standard protocol. mEPIC consists in shortening the original protocol from five to two days of postoperative intraperitoneal chemotherapy. Additionally, instead of solely administering a singular 5-FU bolus per 24 hours-period, mEPIC is based on the De Gramont intravenous regimen and consists of administering one intraperitoneal bolus of 5-FU (400 mg/m2) followed by a 24 hours-intraperitoneal infusion of 5-FU (1200 mg/m2) on postoperative days 1 and 2.

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 data supports the effectiveness of the treatment Modified early post-operative intraperitoneal chemotherapy (mEPIC) for peritoneal cancer?

The research suggests that while early postoperative intraperitoneal chemotherapy (EPIC) is used after surgery for certain types of cancer, its benefits are still debated, with some studies indicating increased complications without clear evidence of improved cancer outcomes. ^{1 2 3 4 5}

How is the mEPIC treatment different from other treatments for peritoneal cancer?

The mEPIC treatment is unique because it involves administering chemotherapy directly into the abdominal cavity shortly after surgery, which is different from standard chemotherapy that is usually given through the bloodstream. This approach aims to target cancer cells more directly in the peritoneal area, potentially improving outcomes for patients with peritoneal cancer. ^{1 2 3 5 6}

Research Team

Mikael Soucisse, MD, FRCSC

Principal Investigator

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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 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]

References

1. England 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. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Early Postoperative Intraperitoneal Chemotherapy for Low-Grade Appendiceal Mucinous Neoplasms with Pseudomyxoma Peritonei: Is it Beneficial? [2018]

3. England 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. [2021]

4. England 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. [2022]

5. Japan pubmed.ncbi.nlm.nih.gov

Comparative analysis of perioperative intraperitoneal chemotherapy regimen in appendiceal and colorectal peritoneal carcinomatosis. [2022]

6. England 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. [2021]