Overview

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).

Eligibility

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