Efficacy of Hyperthermic Intraperitoneal Chemotherapy

NCT04861558 | Recruiting Phase 3 DMC

• 1 other identifier: EFFIPECv5
• Study Type: interventional
• Target: 213
• Locations: 2 countries
• Sites: 5

Brief Summary

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).

Conditions

Colorectal Cancer; Peritoneal Metastases

Outcome Measures

Primary Outcomes (1)

• Recurrence-free survival

  To study the recurrence-free survival (RFS) of patients

  24 months after treatment

Secondary Outcomes (4)

• Overall survival

  5 years after treatment

• Recurrence-free survival

  5 years after treatment

• Postoperative complication rate

  Within 30 days after treatment

• Patient evaluations of quality of life

  3 years after treatment

Study Arms (2)

Standard HIPEC

ACTIVE COMPARATOR

Injection of oxaliplatin 460 mg/m2 and an intraoperational IV of 5-fluorouracil 400 mg/m2, and calcium folinate 60 mg/m2.

Drug: Oxaliplatin

Intensified HIPEC+EPIC

EXPERIMENTAL

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; Drug: Irinotecan; Drug: Oxaliplatin

Interventions

5Fluorouracil DRUG

Injection of 250-850 mg/m2.

Also known as: Fluorouracil Accord, Fluorouracil Tevo

Intensified HIPEC+EPIC

Irinotecan DRUG

Injection of 360 mg/m2

Also known as: Irinotecan Accord, Irinotecan Actavis, Irinotecan Fresenius Kabi

Intensified HIPEC+EPIC

Oxaliplatin DRUG

Injection of 460 mg/m2

Also known as: Oxaliplatin Accord, Oxaliplatin Teva, Oxaliplatin Fresenius Kabi

Intensified HIPEC+EPIC; Standard HIPEC

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of written informed consent prior to any study specific procedures.
• ECOG Performance Status Score 0,1 or 2 alternatively Karnofsky 60-100
• 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 ≤78 years old
• Colorectal cancer with peritoneal metastases +/- liver metastases (maximum 3)
• Concomitant resectable pulmonary metastases are allowed
• 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.

You may not qualify if:

• 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 or liver or lung
• Complex liver-perenchymal sparing surgery or hemihepatectomy procedures are to be excluded.
• Previous CRS or HIPEC
• 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 2-3
• Histopathology of other origin than colorectal cancer

Sponsors & Collaborators

• Uppsala University: lead

Study Sites (5)

INDEPSO

Ahmedabad, India

RECRUITING

Sahlgrenska östra sjukhuset

Gothenburg, Sweden

RECRUITING

Skånes universitetssjukhus

Malmo, Sweden

RECRUITING

Karolinska sjukhuset

Stockholm, Sweden

RECRUITING

Akademiska sjukhuset

Uppsala, 75185, Sweden

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Fluorouracil; Irinotecan; Oxaliplatin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids; Coordination Complexes; Organic Chemicals

Study Officials

• Peter Cashin, MD, PhD

  Uppsala University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Peter Cashin, MD, PhD

CONTACT

+46 (0)18 6174304; peter.cashin@surgsci.uu.se

Lana Ghanipour, MD, PhD

CONTACT

+46 (0)18 6110000; lana.ghanipour@surgsci.uu.se

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2021
• First Posted: April 27, 2021
• Study Start: May 1, 2021
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2029
• Last Updated: May 30, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: To be shared at the time of phase 3 trial publication. Available for 10 years.
• Access Criteria: Access by request only from the corresponding author. Study protocol, SAP, ICF will be publicly available without request.

Locations

SE (4); IN (1)