NCT02244632

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
105

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Sep 2014

Longer than P75 for phase_1

Geographic Reach
4 countries

10 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2014

Completed
16 days until next milestone

First Submitted

Initial submission to the registry

September 17, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 19, 2014

Completed
5.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 30, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 30, 2020

Completed
Last Updated

September 9, 2020

Status Verified

September 1, 2020

Enrollment Period

5.4 years

First QC Date

September 17, 2014

Last Update Submit

September 7, 2020

Conditions

Colorectal Neoplasm

Keywords

Colorectal cancerColorectal carcinomaColorectal tumorsIntestinal NeoplasmGastrointestinal NeoplasmGastrointestinal disease5,10-methylenetetrahydrofolateTetrahydrofolatesTherapeutic usesPharmacokineticsPharmacodynamicsSafety assessments

Outcome Measures

Primary Outcomes (1)

  • 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.

    The patients will be followed during 4 cycles of treatment (8 weeks).

Study Arms (6)

Modufolin / Nordic FLV

EXPERIMENTAL

Modufolin in combination with 5-Fluorouracil only.

Drug: Modufolin (arfolitixorin)Drug: Fluorouracil

Modufolin / Nordic FLOX

EXPERIMENTAL

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

Drug: Modufolin (arfolitixorin)Drug: FluorouracilDrug: Oxaliplatin

Modufolin / Nordic FLIRI

EXPERIMENTAL

Modufolin in combination with 5-Fluorouracil and Irinotecan.

Drug: Modufolin (arfolitixorin)Drug: FluorouracilDrug: Irinotecan

MOFOX

EXPERIMENTAL

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

Drug: Modufolin (arfolitixorin)Drug: FluorouracilDrug: Oxaliplatin

MOFOX / Bevacizumab

EXPERIMENTAL

Modufolin in combination with 5-Fluorouracil, Oxaliplatin and Bevacizumab

Drug: Modufolin (arfolitixorin)Drug: FluorouracilDrug: OxaliplatinDrug: Bevacizumab

MOFIRI

EXPERIMENTAL

Modufolin in combination with 5-Fluorouracil and Irinotecan

Drug: Modufolin (arfolitixorin)Drug: FluorouracilDrug: Irinotecan

Interventions

Modufolin (arfolitixorin)DRUG

IV injection every second week for 8 weeks.

Also known as: [6R] 5,10-methylenetetrahydrofolate, 6R-MTHF, 6R-methylene THF, ISO-901, arfolitixorin
MOFIRIMOFOXMOFOX / BevacizumabModufolin / Nordic FLIRIModufolin / Nordic FLOXModufolin / Nordic FLV
FluorouracilDRUG

IV injection every second week for 8 weeks.

Also known as: 5-FU, 5-Flourouacil, 5-Fluoro-1H,3H-pyrimidine-2,4-dione, Adrucil
MOFIRIMOFOXMOFOX / BevacizumabModufolin / Nordic FLIRIModufolin / Nordic FLOXModufolin / Nordic FLV
OxaliplatinDRUG

IV infusion every second week for 8 weeks.

Also known as: Eloxatin, [(1R,2R)-cyclohexane-1,2-diamine](ethanedioato-O,O')platinum(II), Olatin, Oxamed, Oxitropic
MOFOXMOFOX / BevacizumabModufolin / Nordic FLOX
IrinotecanDRUG

IV infusion every second week for 8 weeks.

Also known as: (+)-(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
MOFIRIModufolin / Nordic FLIRI
BevacizumabDRUG

IV infusion every second week for 8 weeks.

Also known as: Avastin
MOFOX / Bevacizumab

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Advanced metastatic colorectal (Stage IV) cancer verified by biopsy

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

Odense University Hospital

Odense, Denmark

Location

251 General Airforce Hospital

Athens, Greece

Location

Medical School University of Athens, Aretaieio Hospital

Athens, Greece

Location

Metropolitan General Hospital

Athens, Greece

Location

University Genral Hospital Attikon

Athens, Greece

Location

University General Hospital of Heraklion

Irakleio, Greece

Location

Oslo University Hospital - Radiumhospitalet

Oslo, Norway

Location

Oslo University Hospital - Ullevål

Oslo, Norway

Location

Sahlgrenska University Hospital

Gothenburg, 461 85, Sweden

Location

Skaraborg hospital

Skövde, Sweden

Location

Related Publications (2)

  • 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.

    PMID: 36183444DERIVED

  • 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.

    PMID: 33099678DERIVED

MeSH Terms

Conditions

Colorectal NeoplasmsIntestinal NeoplasmsGastrointestinal NeoplasmsGastrointestinal Diseases

Interventions

5,10-methylenetetrahydrofolic acidFluorouracilOxaliplatinIrinotecanBevacizumab

Condition Hierarchy (Ancestors)

Digestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesColonic DiseasesIntestinal DiseasesRectal Diseases

Intervention Hierarchy (Ancestors)

UracilPyrimidinonesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsCoordination ComplexesOrganic ChemicalsCamptothecinAlkaloidsAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Göran Carlsson, MD

    Sahlgrenska University Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 17, 2014

First Posted

September 19, 2014

Study Start

September 1, 2014

Primary Completion

January 30, 2020

Study Completion

January 30, 2020

Last Updated

September 9, 2020

Record last verified: 2020-09

Data Sharing

IPD Sharing
Will not share

Locations

SE(2)GR(5)DK(1)NO(2)