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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02244632
Recruitment Status : Completed
First Posted : September 19, 2014
Last Update Posted : September 9, 2020
Sponsor:
Information provided by (Responsible Party):
Isofol Medical AB

Tracking Information
First Submitted Date  ICMJE September 17, 2014
First Posted Date  ICMJE September 19, 2014
Last Update Posted Date September 9, 2020
Actual Study Start Date  ICMJE September 2014
Actual Primary Completion Date January 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 31, 2017)
Frequency and severity of dose limiting toxicity (DLT) or other Adverse Events (AE) [ Time Frame: The patients will be followed during 4 cycles of treatment (8 weeks). ]
Primary safety variables will consist of monitoring and recording of DLTs and any significant AE that have led to adjustments in the therapy administration.
Original Primary Outcome Measures  ICMJE
 (submitted: September 17, 2014)
  • Frequency and severity of dose limiting toxicity (DLT) or other Adverse Events (AE) (Part 1) [ Time Frame: The patients will be followed during 4 cycles of treatment (8 weeks). ]
    Primary outcome measure of Part 1: Characterization (frequency and severity) of dose limiting toxicity (DLT) or other AEs associated with the administration of 5-FU/Modufolin at each Modufolin dose level
  • Number of patients with adjusted Oxaliplatin/5-FU dose due to presence of dose limiting toxicity (DLT) (Part 2) [ Time Frame: The patients will be followed during 4 cycles of treatment (8 weeks). ]
    Primary outcome measure of Part 2: Number patients with adjusted Oxaliplatin/5-FU dose due to presence of related toxicity
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: September 17, 2014)
  • Number and severity of AEs or abnormal laboratory test [ Time Frame: Lab tests performed on Day 7 and Day 12 of each cycle. The patients will be followed during 4 cycles of treatment (8 weeks). ]
  • CT scan or MRI [ Time Frame: Before start and after 8 weeks of treatment (4 cycles) ]
    Determination of Objective Response Rate (ORR) after 4 cycles of chemotherapy
  • Deoxyuridine (dU) levels before and 24 hours after treatment [ Time Frame: On Day 1 of treatment cycle 1 and in cycle 4 ]
  • Analyse of levels of 5,10- MTHF, 5-methyl-THF, and THF [ Time Frame: Samples will be collected on Day 1 of cycle 1 and Day 1 of Cycle 4 ]
    For analysis of plasma pharmacokinetics
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: September 17, 2014)
Number and severity of AEs or abnormal laboratory test [ Time Frame: Lab tests performed on Day 7 and Day 12 of each cycle. The patients will be followed during 4 cycles of treatment (8 weeks). ]
Exploratory endpoints: Association between the presence of DLTs and other AEs or abnormal laboratory test results and the pharmacokinetics of folates following administration of Modufolin
 
Descriptive Information
Brief Title  ICMJE Modufolin (Arfolitixorin) in Combination With 5-Fluorouracil Alone or Together With Oxaliplatin or Irinotecan in Colorectal Cancer
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Neoplasm
Intervention  ICMJE
  • Drug: Modufolin (arfolitixorin)
    IV injection every second week for 8 weeks.
    Other Names:
    • [6R] 5,10-methylenetetrahydrofolate
    • 6R-MTHF
    • 6R-methylene THF
    • ISO-901
    • arfolitixorin
  • Drug: Fluorouracil
    IV injection every second week for 8 weeks.
    Other Names:
    • 5-FU
    • 5-Flourouacil
    • 5-Fluoro-1H,3H-pyrimidine-2,4-dione
    • Adrucil
  • Drug: Oxaliplatin
    IV infusion every second week for 8 weeks.
    Other Names:
    • Eloxatin
    • [(1R,2R)-cyclohexane-1,2-diamine](ethanedioato-O,O')platinum(II)
    • Olatin
    • Oxamed
    • Oxitropic
  • Drug: Irinotecan
    IV infusion every second week for 8 weeks.
    Other Names:
    • (+)-(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
  • Drug: Bevacizumab
    IV infusion every second week for 8 weeks.
    Other Name: Avastin
Study Arms  ICMJE
  • Experimental: Modufolin / Nordic FLV
    Modufolin in combination with 5-Fluorouracil only.
    Interventions:
    • Drug: Modufolin (arfolitixorin)
    • Drug: Fluorouracil
  • Experimental: Modufolin / Nordic FLOX
    Modufolin in combination with 5-Fluorouracil and Oxaliplatin according to Nordic FLOX regime
    Interventions:
    • Drug: Modufolin (arfolitixorin)
    • Drug: Fluorouracil
    • Drug: Oxaliplatin
  • Experimental: Modufolin / Nordic FLIRI
    Modufolin in combination with 5-Fluorouracil and Irinotecan.
    Interventions:
    • Drug: Modufolin (arfolitixorin)
    • Drug: Fluorouracil
    • Drug: Irinotecan
  • Experimental: MOFOX
    Modufolin in combination with 5-Fluorouracil and Oxaliplatin according to mFOLFOX-6 regime
    Interventions:
    • Drug: Modufolin (arfolitixorin)
    • Drug: Fluorouracil
    • Drug: Oxaliplatin
  • Experimental: MOFOX / Bevacizumab
    Modufolin in combination with 5-Fluorouracil, Oxaliplatin and Bevacizumab
    Interventions:
    • Drug: Modufolin (arfolitixorin)
    • Drug: Fluorouracil
    • Drug: Oxaliplatin
    • Drug: Bevacizumab
  • Experimental: MOFIRI
    Modufolin in combination with 5-Fluorouracil and Irinotecan
    Interventions:
    • Drug: Modufolin (arfolitixorin)
    • Drug: Fluorouracil
    • Drug: Irinotecan
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 18, 2020)
105
Original Estimated Enrollment  ICMJE
 (submitted: September 17, 2014)
24
Actual Study Completion Date  ICMJE January 30, 2020
Actual Primary Completion Date January 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Advanced metastatic colorectal (Stage IV) cancer verified by biopsy

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Denmark,   Greece,   Norway,   Sweden
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02244632
Other Study ID Numbers  ICMJE ISO-CC-005
2014-001862-84 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Isofol Medical AB
Study Sponsor  ICMJE Isofol Medical AB
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Göran Carlsson, MD Sahlgrenska University Hospital, Sweden
PRS Account Isofol Medical AB
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP