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

NCT05913674 | Recruiting Phase 2 DMC

• 1 other identifier: CER-CEMTL 2023-3236
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Peritoneal Carcinomatosis; Appendiceal Neoplasms; Colorectal Cancer Metastatic

Keywords

Intraperitoneal chemotherapy; Early post-operative intraperitoneal chemotherapy; Fluorouracil; Hyperthermic intraperitoneal chemotherapy; Cytoreductive surgery; mEPIC

Outcome Measures

Primary Outcomes (1)

• Feasibility of mEPIC

  Evaluate mEPIC completion rate in patients with colorectal and appendicular cancer with peritoneal carcinomatosis treated with CRS and HIPEC and followed by mEPIC in a tertiary Canadian centre.

  2 days (assessed at the end of mEPIC protocol).

Secondary Outcomes (2)

• Safety of mEPIC

  Up to 3 weeks (assessed during the hospitalization following the participant's surgery).

• Satisfaction of care team

  2 days (assessed during mEPIC protocol)

Study Arms (1)

mEPIC

EXPERIMENTAL

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.

Drug: Modified early post-operative intraperitoneal chemotherapy (mEPIC)

Interventions

Modified early post-operative intraperitoneal chemotherapy (mEPIC) DRUG

On post-operative days 1 and 2, an abdominal reservoir is obtained by administering 1000 mL of plasmalyte with 50 mEq NaHCO3 via a Tenckhoff catheter. Participants will then receive an intraperitoneal fluorouracil bolus of 400 mg/m2 administered over 1 to 2 minutes followed by a continuous intraperitoneal fluorouracil infusion of 1200 mg/m2 over the next 24 hours. During the continuous intraperitoneal infusion of fluorouracil, 50 mg of folinic acid is administered intravenously. After completion of mEPIC day 1, the perfusate is drained out before starting mEPIC day 2.

Also known as: mEPIC

mEPIC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient's age 18 years or older, both genders.
• In good general health as evidenced by an ECOG score of 0 or 1.
• Histological diagnosis of appendicular or colorectal tumors with peritoneal carcinomatosis, either synchronous (\< 12 months after primary diagnosis) or metachronous (\>12 months after the primary diagnosis)
• Complete staging defined as: (1)Computed tomography (CT) scan of the chest, abdomen and pelvis. (2) Positron emission tomography (PET) scan when clinically appropriate. (3) Diagnostic laparoscopy reporting Peritoneal carcinomatosis index (PCI) +/- biopsy
• Meets criteria for recommendation by combined multidisciplinary team and tumor board for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) followed by mEPIC
• Surgery must be performed within 4-6 weeks following the end of neoadjuvant therapy or 4-6 weeks following the patient's enrollment if no neoadjuvant therapy needed.
• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the study duration
• Hematology: Absolute neutrophil count (ANC) ≥ 1,500/ μL; Platelets \> 75,000/ μL.
• Adequate Renal function Creatinine \<1.5 x the upper limit of normal (ULN) or calculated creatinine clearance of ≥ 50ml/min.
• Adequate Hepatic function: Bilirubin less than 1.5mg/dL; (except in patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0mg/dL).

You may not qualify if:

• Pre-cytoreductive surgery:
• Other malignancies other than appendicular and colorectal neoplasms with peritoneal involvement
• Inability to complete cytoreductive surgery (ECOG 2 or above) or any patient deemed unfit for surgery
• Known allergic reaction or major toxicity to Fluorouracil
• Contraindications to Fluorouracil, including history of coronary spasm and/or known dihydropyrimidine dehydrogenase deficiency
• Pregnancy
• Evidence of extensive intraperitoneal adhesions at the time of surgery which prohibits intraperitoneal therapy, as determined by the operating surgeon.
• Any condition that would preclude the ability to deliver appropriate intraperitoneal (IP) therapy.
• Post-cytoreductive surgery:
• Patient deemed not medically suitable to receive mEPIC protocol according to surgical team
• Uncorrected coagulopathy and/or thrombocytopenia and/or neutropenia
• Active infection
• Hemodynamic and / or respiratory compromise
• Evidence of extensive intraperitoneal adhesions at the time of surgery which prohibits intraperitoneal therapy, as determined by the operating surgeon.
• Any condition that would preclude the ability to deliver appropriate IP therapy.

Sponsors & Collaborators

• Ciusss de L'Est de l'Île de Montréal: lead
• Maisonneuve-Rosemont Hospital: collaborator

Study Sites (1)

Hôpital Maisonneuve-Rosemont

Montreal, Quebec, H1T 2M4, Canada

RECRUITING

Related Publications (15)

• 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.

  PMID: 31667329 BACKGROUND

• Cunliffe WJ, Sugarbaker PH. Gastrointestinal malignancy: rationale for adjuvant therapy using early postoperative intraperitoneal chemotherapy. Br J Surg. 1989 Oct;76(10):1082-90. doi: 10.1002/bjs.1800761030.

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• Sugarbaker PH, Graves T, DeBruijn EA, Cunliffe WJ, Mullins RE, Hull WE, Oliff L, Schlag P. Early postoperative intraperitoneal chemotherapy as an adjuvant therapy to surgery for peritoneal carcinomatosis from gastrointestinal cancer: pharmacological studies. Cancer Res. 1990 Sep 15;50(18):5790-4.

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• Pestieau SR, Schnake KJ, Stuart OA, Sugarbaker PH. Impact of carrier solutions on pharmacokinetics of intraperitoneal chemotherapy. Cancer Chemother Pharmacol. 2001 Mar;47(3):269-76. doi: 10.1007/s002800000214.

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• 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.

  PMID: 26751236 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.

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• 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.

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MeSH Terms

Conditions

Peritoneal Neoplasms; Appendiceal Neoplasms

Condition Hierarchy (Ancestors)

Abdominal Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Peritoneal Diseases; Cecal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Cecal Diseases; Intestinal Diseases

Study Officials

• Mikael Soucisse, MD, FRCSC

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mikael Soucisse, MD, FRCSC

CONTACT

514-252-3400; mikael.lefebvre.soucisse@umontreal.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2023
• First Posted: June 22, 2023
• Study Start: August 1, 2024
• Primary Completion: January 1, 2026
• Study Completion: January 1, 2026
• Last Updated: August 21, 2024

Record last verified: 2024-08

Locations

CA (1)