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Modufolin (Arfolitixorin) in Combination With 5-Fluorouracil Alone or Together With Oxaliplatin or Irinotecan in Colorectal Cancer

Primary Purpose

Colorectal Neoplasm

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Modufolin (arfolitixorin)
Fluorouracil
Oxaliplatin
Irinotecan
Bevacizumab
Sponsored by
Isofol Medical AB
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Neoplasm focused on measuring Colorectal cancer, Colorectal carcinoma, Colorectal tumors, Intestinal Neoplasm, Gastrointestinal Neoplasm, Gastrointestinal disease, 5,10-methylenetetrahydrofolate, Tetrahydrofolates, Therapeutic uses, Pharmacokinetics, Pharmacodynamics, Safety assessments

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Advanced metastatic colorectal (Stage IV) cancer verified by biopsy

Sites / Locations

  • Odense University Hospital
  • 251 General Airforce Hospital
  • Medical School University of Athens, Aretaieio Hospital
  • Metropolitan General Hospital
  • University Genral Hospital Attikon
  • University General Hospital of Heraklion
  • Oslo University Hospital - Radiumhospitalet
  • Oslo University Hospital - Ullevål
  • Sahlgrenska University Hospital
  • Skaraborg hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Modufolin / Nordic FLV

Modufolin / Nordic FLOX

Modufolin / Nordic FLIRI

MOFOX

MOFOX / Bevacizumab

MOFIRI

Arm Description

Modufolin in combination with 5-Fluorouracil only.

Modufolin in combination with 5-Fluorouracil and Oxaliplatin according to Nordic FLOX regime

Modufolin in combination with 5-Fluorouracil and Irinotecan.

Modufolin in combination with 5-Fluorouracil and Oxaliplatin according to mFOLFOX-6 regime

Modufolin in combination with 5-Fluorouracil, Oxaliplatin and Bevacizumab

Modufolin in combination with 5-Fluorouracil and Irinotecan

Outcomes

Primary Outcome Measures

Frequency and severity of dose limiting toxicity (DLT) or other Adverse Events (AE)
Primary safety variables will consist of monitoring and recording of DLTs and any significant AE that have led to adjustments in the therapy administration.

Secondary Outcome Measures

Full Information

First Posted
September 17, 2014
Last Updated
September 7, 2020
Sponsor
Isofol Medical AB
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1. Study Identification

Unique Protocol Identification Number
NCT02244632
Brief Title
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

2. Study Status

Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
September 2014 (Actual)
Primary Completion Date
January 30, 2020 (Actual)
Study Completion Date
January 30, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Isofol Medical AB

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
105 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Modufolin / Nordic FLV
Arm Type
Experimental
Arm Description
Modufolin in combination with 5-Fluorouracil only.
Arm Title
Modufolin / Nordic FLOX
Arm Type
Experimental
Arm Description
Modufolin in combination with 5-Fluorouracil and Oxaliplatin according to Nordic FLOX regime
Arm Title
Modufolin / Nordic FLIRI
Arm Type
Experimental
Arm Description
Modufolin in combination with 5-Fluorouracil and Irinotecan.
Arm Title
MOFOX
Arm Type
Experimental
Arm Description
Modufolin in combination with 5-Fluorouracil and Oxaliplatin according to mFOLFOX-6 regime
Arm Title
MOFOX / Bevacizumab
Arm Type
Experimental
Arm Description
Modufolin in combination with 5-Fluorouracil, Oxaliplatin and Bevacizumab
Arm Title
MOFIRI
Arm Type
Experimental
Arm Description
Modufolin in combination with 5-Fluorouracil and Irinotecan
Intervention Type
Drug
Intervention Name(s)
Modufolin (arfolitixorin)
Other Intervention Name(s)
[6R] 5,10-methylenetetrahydrofolate, 6R-MTHF, 6R-methylene THF, ISO-901, arfolitixorin
Intervention Description
IV injection every second week for 8 weeks.
Intervention Type
Drug
Intervention Name(s)
Fluorouracil
Other Intervention Name(s)
5-FU, 5-Flourouacil, 5-Fluoro-1H,3H-pyrimidine-2,4-dione, Adrucil
Intervention Description
IV injection every second week for 8 weeks.
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Other Intervention Name(s)
Eloxatin, [(1R,2R)-cyclohexane-1,2-diamine](ethanedioato-O,O')platinum(II), Olatin, Oxamed, Oxitropic
Intervention Description
IV infusion every second week for 8 weeks.
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Other Intervention Name(s)
(+)-(4S)-4,11-Dietyl-4-hydroxi-9-[(4-piperidinopiperidino)karbonyloxi]-1H-pyrano[3¢,4¢:6,7]indolizino[1,2-b]kinolin-3,14-(4H,12H)dion, Irinosor, Campto, Namedica
Intervention Description
IV infusion every second week for 8 weeks.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
IV infusion every second week for 8 weeks.
Primary Outcome Measure Information:
Title
Frequency and severity of dose limiting toxicity (DLT) or other Adverse Events (AE)
Description
Primary safety variables will consist of monitoring and recording of DLTs and any significant AE that have led to adjustments in the therapy administration.
Time Frame
The patients will be followed during 4 cycles of treatment (8 weeks).

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Advanced metastatic colorectal (Stage IV) cancer verified by biopsy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Göran Carlsson, MD
Organizational Affiliation
Sahlgrenska University Hospital, Sweden
Official's Role
Principal Investigator
Facility Information:
Facility Name
Odense University Hospital
City
Odense
Country
Denmark
Facility Name
251 General Airforce Hospital
City
Athens
Country
Greece
Facility Name
Medical School University of Athens, Aretaieio Hospital
City
Athens
Country
Greece
Facility Name
Metropolitan General Hospital
City
Athens
Country
Greece
Facility Name
University Genral Hospital Attikon
City
Athens
Country
Greece
Facility Name
University General Hospital of Heraklion
City
Iráklion
Country
Greece
Facility Name
Oslo University Hospital - Radiumhospitalet
City
Oslo
Country
Norway
Facility Name
Oslo University Hospital - Ullevål
City
Oslo
Country
Norway
Facility Name
Sahlgrenska University Hospital
City
Göteborg
ZIP/Postal Code
461 85
Country
Sweden
Facility Name
Skaraborg hospital
City
Skövde
Country
Sweden

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
36183444
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.
Results Reference
derived
PubMed Identifier
33099678
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.
Results Reference
derived

Learn more about this trial

Modufolin (Arfolitixorin) in Combination With 5-Fluorouracil Alone or Together With Oxaliplatin or Irinotecan in Colorectal Cancer

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