Technical Feasibility of Modified Early Post-Operative Intraperitoneal Chemotherapy (mEPIC)

Summary

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.

Timeline

Start

2026-05-01

Primary completion

2028-05

Completion

2028-09

Publications

• Background Soucisse ML, Liauw W, Hicks G, Morris DL. Early postoperative intraperitoneal chemotherapy for lower gastrointestinal neoplasms with peritoneal metastasis: a systematic review and critical analysis. Pleura Peritoneum. 2019 Oct 4;4(3):20190007. doi: 10.1515/pp-2019-0007. eCollection 2019 Sep 1.
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• Background Cashin PH, Mahteme H, Spang N, Syk I, Frodin JE, Torkzad M, Glimelius B, Graf W. Cytoreductive surgery and intraperitoneal chemotherapy versus systemic chemotherapy for colorectal peritoneal metastases: A randomised trial. Eur J Cancer. 2016 Jan;53:155-62. doi: 10.1016/j.ejca.2015.09.017. Epub 2016 Jan 2.
• Background Huang Y, Alzahrani NA, Liauw W, Traiki TB, Morris DL. Early Postoperative Intraperitoneal Chemotherapy for Low-Grade Appendiceal Mucinous Neoplasms with Pseudomyxoma Peritonei: Is it Beneficial? Ann Surg Oncol. 2017 Jan;24(1):176-183. doi: 10.1245/s10434-016-5529-0. Epub 2016 Oct 7.
• Background Lam JY, McConnell YJ, Rivard JD, Temple WJ, Mack LA. Hyperthermic intraperitoneal chemotherapy + early postoperative intraperitoneal chemotherapy versus hyperthermic intraperitoneal chemotherapy alone: assessment of survival outcomes for colorectal and high-grade appendiceal peritoneal carcinomatosis. Am J Surg. 2015 Sep;210(3):424-30. doi: 10.1016/j.amjsurg.2015.03.008. Epub 2015 May 12.
• Background Hayler R, Lockhart K, Barat S, Cheng E, Mui J, Shamavonian R, Ahmadi N, Alzahrani N, Liauw W, Morris D. Survival benefits with EPIC in addition to HIPEC for low grade appendiceal neoplasms with pseudomyxoma peritonei: a propensity score matched study. Pleura Peritoneum. 2023 Mar 16;8(1):27-35. doi: 10.1515/pp-2022-0205. eCollection 2023 Mar.
• Background Van der Speeten K, Govaerts K, Stuart OA, Sugarbaker PH. Pharmacokinetics of the perioperative use of cancer chemotherapy in peritoneal surface malignancy patients. Gastroenterol Res Pract. 2012;2012:378064. doi: 10.1155/2012/378064. Epub 2012 Jun 13.
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• Background Kerr DJ, Young AM, Neoptolemos JP, Sherman M, Van-Geene P, Stanley A, Ferry D, Dobbie JW, Vincke B, Gilbert J, el Eini D, Dombros N, Fountzilas G. Prolonged intraperitoneal infusion of 5-fluorouracil using a novel carrier solution. Br J Cancer. 1996 Dec;74(12):2032-5. doi: 10.1038/bjc.1996.672.

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