Clinical trial NCT02244632: Modufolin (Arfolitixorin) in Combination With 5-Fluorouracil Alone or Together With Oxaliplatin or Irinotecan in Colorectal Cancer
Official title: An Open-label, Multiple-site, Phase I/II Dose Cohort Trial of [6R] 5,10-Methylene Tetrahydrofolate (Modufolin®) in Combination With a Fixed Dose of 5-Fluorouracil (5-FU) Alone or Together With a Fixed Dose of Oxaliplatin or Irinotecan in Patients With Stage IV Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Colorectal Neoplasm
Keywords: Colorectal cancer
Colorectal carcinoma
Colorectal tumors
Intestinal Neoplasm
Gastrointestinal Neoplasm
Gastrointestinal disease
5,10-methylenetetrahydrofolate
Tetrahydrofolates
Therapeutic uses
Pharmacokinetics
Pharmacodynamics
Safety assessments
Lead sponsor: Isofol Medical AB
Sponsor class: INDUSTRY
First posted: 2014-09-19
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose is to characterise the tolerability of Modufolin (arfolitixorin) in combination with 5-FU alone, in combination with 5-FU and Oxaliplatin, in combination with 5-FU and Irinotecan and in combination with 5-FU, Oxaliplatin and Bevacizumab.

Another purpose is to investigate 4 doses of Modufolin to identify the best dose for further assessment.

Detailed description: The study will investigate the tolerability of Modufolin at four (4) different dose levels (30 to 240 mg/m2) in therapy combinations with the chemotherapeutic agents 5-FU, Oxaliplatin +/- bevcizumab, and Irinotecan.

When the selected phase 2 dose is determined, 40 additional patients, will be included in the study in order to acquire more data on the safety and tolerability of Modufolin at this dose level. Twenty (20) of these additional patients will be treated in with Oxaliplatin, 20 with Irinotecan.

Eligibility criteria: Inclusion Criteria:

Advanced metastatic colorectal (Stage IV) cancer verified by biopsy

Primary outcomes:
measure: Frequency and severity of dose limiting toxicity (DLT) or other Adverse Events (AE)
timeFrame: The patients will be followed during 4 cycles of treatment (8 weeks).
Secondary outcomes:
Other outcomes:
Locations:
city: Odense
country: Denmark
facility: Odense University Hospital
city: Athens
country: Greece
facility: 251 General Airforce Hospital
city: Athens
country: Greece
facility: Medical School University of Athens, Aretaieio Hospital
city: Athens
country: Greece
facility: Metropolitan General Hospital
city: Athens
country: Greece
facility: University Genral Hospital Attikon
city: Iráklion
country: Greece
facility: University General Hospital of Heraklion
city: Oslo
country: Norway
facility: Oslo University Hospital - Radiumhospitalet
city: Oslo
country: Norway
facility: Oslo University Hospital - Ullevål
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: Skövde
country: Sweden
facility: Skaraborg hospital
Study officials:
affiliation: Sahlgrenska University Hospital
name: Göran Carlsson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Carlsson G, Koumarianou A, Guren TK, Haux J, Katsaounis P, Kentepozidis N, Pfeiffer P, Braendengen M, Mavroudis D, Taflin H, Skintemo L, Tell R, Papadimitriou C. A phase I/II study of arfolitixorin and 5-fluorouracil in combination with oxaliplatin (plus or minus bevacizumab) or irinotecan in metastatic colorectal cancer. ESMO Open. 2022 Oct;7(5):100589. doi: 10.1016/j.esmoop.2022.100589. Epub 2022 Sep 29.
citation: Taflin H, Odin E, Carlsson G, Tell R, Gustavsson B, Wettergren Y. Plasma deoxyuridine as a surrogate marker for toxicity and early clinical response in patients with metastatic colorectal cancer after 5-FU-based therapy in combination with arfolitixorin. Cancer Chemother Pharmacol. 2021 Jan;87(1):31-41. doi: 10.1007/s00280-020-04173-2. Epub 2020 Oct 24.