NCT04126655

Modelle 001, TS-inhibition in Colorectal Liver Metastases Comparing Arfolitixorin and Calciumfolinate

A Randomised Phase II Study Investigating Two Doses of Arfolitixorin Compared to Calciumfolinate Together With 5- Fluorouracil on TS Inhibition in Tumour and Adjacent Hepatic Tissue for Patients With Liver Metastases From Colorectal Cancer

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Vastra Gotaland Region · Other Government
• Sex: All
• Age: 18 Years – 100 Years
• Healthy volunteers: Not accepted

Summary

A study that is blinded to the patient and the investigator where the combination of Arfolitixorin + 5-FU is compared to Calciumfolinate + 5-FU. The patients will be randomised and will receive the above described combination as IV bolus injections, peroperatively in conjuction with collection of the first tissue sample. A low dose (30 mg) and a high dose (120) mg of Arfolitixorin will be used in order to investigate the relation between dose of Arfolitixorin and TS-inhibition.

Detailed description

Arfolitixorin (\[6R\] 5,10-methylenetetrahydrofolate) is a folate based biomodulator designed to replace leucovorin. Arfolitixorin is the key active metabolite of leucovorin (LV) and does in contrast to LV not require enzymatic metabolic activation. In clinical practice, LV is administered in the form of Calciumfolinate. A hypothesis is therefore that patients which are not capable of metabolizing LV could have a better antitumoral effect with Arfolitixorin administration. The antitumoural effect could be measured as inhibition of the enzyme thymidylate synthase, an enzyme essential for DNA synthesis. Primary objective The primary objective is to compare the properties of Arfolitixorin and Calciumfolinate together with 5-fluorouracil (5-FU) on thymidylate synthase (TS) (i.e. measured as thymidylate synthase inhibition) in tumour and adjacent liver tissue in patients with liver metastases from colorectal cancer receiving a peroperative intravenous administration of Arfolitixorin or Calciumfolinate. Secondary objectives To study safety in terms of adverse events and laboratory measurements; haematology and clinical chemistry. To explore differences in pharmacokinetics of folates and folate metabolites in plasma. To study gene expression in tumour and adjacent hepatic tissue and its correlation to tissue concentration. To investigate the relation between the levels of deoxyuridine (dU) in plasma with the amount of TS inhibition in tumour tissue, in order to evaluate dU as a surrogate marker for TS-inhibition. Study population: Thirty adult patients with colorectal cancer and liver metastases, indicated for surgical removal will be randomised.

Conditions

• Metastatic Colorectal Cancer

Interventions

Type	Name	Description
DRUG	Arfolitixorin	Per operative administration of 5-FU with Arfolitixorin or Calciumfolinate

Timeline

• Start date: 2020-02-05
• Primary completion: 2021-10-01
• Completion: 2021-11-01
• First posted: 2019-10-15
• Last updated: 2020-08-27

Locations

1 site across 1 country: Sweden