Efficacy of Hyperthermic Intraperitoneal Chemotherapy (EFFIPEC)

EFFIPEC - Efficacy of Hyperthermic Intraperitoneal Chemotherapy, Single-arm Phase I Study, Followed by an Open-label, Randomized, Controlled Registry-based Phase III Trial

A dose titration study and a combined superiority registry-based open-label randomized control trial is planned to answer the trial objectives. The study will be registry-based to allow simpler and more comprehensive follow-up. Patients with colorectal cancer will be treated with cytoreductive surgery (CRS) together with either standard oxaliplatin HIPEC (the control for the efficacy study) or oxaliplatin/irinotecan HIPEC in combination with 5-FU 24-hour EPIC. The 5-FU will be administered postoperatively when the abdomen is completely sutured. The drug is divided equally into 2 injections of 200 ml each and injected through two abdominal drains that are clamped for 16 hours.

For dose escalation, the titration groups (á 3 or 6 patients) are followed for 30 days postoperatively after which the Data Monitoring Committee (DMC) will determine whether or not to increase the 5-FU dose for the following group of patients.

To study efficacy, randomization is performed intraoperatively. The patient is followed up postoperatively for a total of 3 years for the secondary endpoints which may be extended by the study committee to 5 years. Since the trial is registry based, the long-term follow-up does not require separate eCRF evaluations. These evaluations can be automatically retrieved from the registry - both recurrence data, quality of life, and morbidity data. Some specific eCRF evaluations will be integrated as a separate study part of the HIPEC registry, such as inclusion/exclusion criteria and adverse event reporting (including SUSAR reporting).

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Peritoneal Metastases
• Intervention / Treatment: Drug: Oxaliplatin; Drug: 5Fluorouracil; Drug: Irinotecan

Detailed Description

Not detailed description entered.

• Study Type: Interventional
• Enrollment (Estimated): 356
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Peter Cashin, MD, PhD; Phone Number: +46 (0)18 6174304; Email: peter.cashin@surgsci.uu.se
• Study Contact Backup: Name: Lana Ghanipour, MD, PhD; Phone Number: +46 (0)18 6110000; Email: lana.ghanipour@surgsci.uu.se

Study Locations

• Sweden
  • Gothenburg, Sweden
    • Recruiting
    • Sahlgrenska östra sjukhuset
    • Contact: Elinor Bexe-Lindskog, MD,PhD; Email: elinor.bexe_lindskog@vgregion.se
    • Principal Investigator: Elinor ö Bexe-Lindskog, MD, PhD
  • Malmö, Sweden
    • Recruiting
    • Skånes universitetssjukhus
    • Contact: Ingvar Syk, MD, PhD; Email: ingvar_syk@telia.com
    • Principal Investigator: Ingvar Syk, MD, PhD
  • Stockholm, Sweden
    • Recruiting
    • Karolinska Sjukhuset
    • Contact: Gabriella Jansson Palmer; Email: gabriella.jansson-palmer@sll.se
    • Principal Investigator: Gabriella Jansson Palmer, MD, PhD
  • Uppsala, Sweden, 75185
    • Recruiting
    • Akademiska sjukhuset
    • Contact: Lana Ghanipour; Email: lana.ghanipour@akademiska.se
    • Principal Investigator: Lana Ghanipour, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Provision of written informed consent prior to any study specific procedures.
• ECOG Performance Status Score 0,1 or 2
• Adequate kidney, liver, bone marrow function according to laboratory tests
• For females of childbearing potential, a negative pregnancy test must be documented
• ≥ 18 years old and <75 years old
• Colorectal cancer with peritoneal metastases
• All patients deemed eligible for CRS and HIPEC according to clinical routine management during a HIPEC multidisciplinary board at each respective hospital can be included.

Exclusion Criteria:

• Previous severe toxicity/allergic reactions to systemic chemotherapy agents oxaliplatin or irinotecan or 5-fluorouracil
• Unable to tolerate intensified HIPEC treatment due to comorbidity
• Metastasis other than peritoneum
• Pregnant or lactating (nursing) women
• Active infections requiring antibiotics
• Active liver disease with positive serology for active hepatitis B, C, or known HIV
• Concurrent administration of any cancer therapy other than planned study treatment within 4 weeks prior to and up to 4 weeks after study treatment
• Incomplete cytoreduction defined as completeness of cytoreduction score 1-3
• Histopathology of other origin than colorectal cancer

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard HIPEC; Injection of oxaliplatin 460 mg/m2 and an intraoperational IV of 5-fluorouracil 400 mg/m2, and calcium folinate 60 mg/m2.	Drug: Oxaliplatin; Injection of 460 mg/m2; Other Names: Oxaliplatin Accord; Oxaliplatin Teva; Oxaliplatin Fresenius Kabi
Experimental: Intensified HIPEC+EPIC; Injection of irinotecan 360 mg/m2 and 5-fluorouracil 24-hr EPIC 250-850 mg/m2 in combination with Oxaliplatin 360 mg/m2 and an intraoperational IV of 5-fluorouracil bolus 400 mg/m2 with calcium folinate 60mg/m2. The EPIC treatment is given after the abdomen is completely sutured in the operating theater. The dose will be divided equally into 2 injections á 200ml each through two abdominal drains.	Drug: 5Fluorouracil; Injection of 250-850 mg/m2.; Other Names: Fluorouracil Accord; Fluorouracil Tevo; Drug: Irinotecan; Injection of 360 mg/m2; Other Names: Irinotecan Accord; Irinotecan Actavis; Irinotecan Fresenius Kabi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence-free survival	To study the recurrence-free survival (RFS) of patients	12 months after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Survival is followed through the HIPEC registry.	5 years after treatment
Recurrence-free survival	Survival is followed through the HIPEC registry. The RECIST criteria are used to determine recurrence and site of first recurrence	5 years after treatment
Postoperative complication rate	Morbidity is registered in the HIPEC registry within 30 days of treatment administration.	Within 30 days after treatment
Patient evaluations of quality of life	EORTC QLQ questionnaire filled out at baseline, 12 and 36 months after surgery using the established QoL database.	3 years after treatment

Collaborators and Investigators

• Sponsor: Uppsala University
• Investigators: Principal Investigator: Peter Cashin, MD, PhD, Uppsala University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2021
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: April 6, 2021
• First Submitted That Met QC Criteria: April 26, 2021
• First Posted (Actual): April 27, 2021

Study Record Updates

• Last Update Posted (Actual): December 8, 2023
• Last Update Submitted That Met QC Criteria: December 1, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Body Temperature Changes; Heat Stress Disorders; Hyperthermia; Fever; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Fluorouracil; Oxaliplatin; Irinotecan
• Other Study ID Numbers: EFFIPEC01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Completely anonymized IPD will be shared. All dates, HIPEC center treatment, referral city, and personal identification will be removed.
• IPD Sharing Time Frame: To be shared at the time of phase 3 trial publication. Available for 10 years.
• IPD Sharing Access Criteria: Access by request only from the corresponding author. Study protocol, SAP, ICF will be publicly available without request.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No