Colorectal NeoplasmPhase 1/2NCT02244632
Modufolin (Arfolitixorin) in Combination With 5-Fluorouracil Alone or Together With Oxaliplatin or Irinotecan in Colorectal Cancer
A Phase 1/2 study testing Modufolin (arfolitixorin), Fluorouracil and Oxaliplatin in people with Colorectal Neoplasm, run by Isofol Medical AB at 10 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Neoplasm
- What is being tested?
- Modufolin (arfolitixorin), Fluorouracil and Oxaliplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 105 participants
- Where
- 10 sitesin 4 countries
- Study dates
- Sep 2014to 30 Jan 2020
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Advanced metastatic colorectal (Stage IV) cancer verified by biopsy
Who cannot join
None listed.
Trial locations and contacts
10 sites in 4 countries.
10 sites in 4 countries
Greece5 sites
251 General Airforce Hospital
Athens
Medical School University of Athens, Aretaieio Hospital
Athens
Metropolitan General Hospital
Athens
University Genral Hospital Attikon
Athens
University General Hospital of Heraklion
Irakleio
Norway2 sites
Oslo University Hospital - Radiumhospitalet
Oslo
Oslo University Hospital - Ullevål
Oslo
Sweden2 sites
Sahlgrenska University Hospital
Gothenburg, 461 85
Skaraborg hospital
Skövde
About this study
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
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.
Read the 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.
- Conditions
- Colorectal Neoplasm
- Being tested
- Modufolin (arfolitixorin), Fluorouracil, Oxaliplatin, Irinotecan, Bevacizumab
- Keywords
- Colorectal cancer, Colorectal carcinoma, Colorectal tumors, Intestinal Neoplasm, Gastrointestinal Neoplasm, Gastrointestinal disease, 5,10-methylenetetrahydrofolate, Tetrahydrofolates, Therapeutic uses, Pharmacokinetics, Pharmacodynamics, Safety assessments
- Medical subject headings
- Colorectal Neoplasms, Intestinal Neoplasms, Gastrointestinal Neoplasms, Gastrointestinal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Modufolin (arfolitixorin)Drug
Also called [6R] 5,10-methylenetetrahydrofolate, 6R-MTHF, 6R-methylene THF, ISO-901
IV injection every second week for 8 weeks.
FluorouracilDrug
Also called 5-FU, 5-Flourouacil, 5-Fluoro-1H,3H-pyrimidine-2,4-dione, Adrucil
IV injection every second week for 8 weeks.
OxaliplatinDrug
Also called Eloxatin, [(1R,2R)-cyclohexane-1,2-diamine](ethanedioato-O,O')platinum(II), Olatin, Oxamed
IV infusion every second week for 8 weeks.
IrinotecanDrug
Also called (+)-(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
IV infusion every second week for 8 weeks.
BevacizumabDrug
Also called Avastin
IV infusion every second week for 8 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Modufolin / Nordic FLV | Experimental | Modufolin in combination with 5-Fluorouracil only. Receives: Drug: Modufolin (arfolitixorin); Drug: Fluorouracil |
| Modufolin / Nordic FLOX | Experimental | Modufolin in combination with 5-Fluorouracil and Oxaliplatin according to Nordic FLOX regime Receives: Drug: Modufolin (arfolitixorin); Drug: Fluorouracil; Drug: Oxaliplatin |
| Modufolin / Nordic FLIRI | Experimental | Modufolin in combination with 5-Fluorouracil and Irinotecan. Receives: Drug: Modufolin (arfolitixorin); Drug: Fluorouracil; Drug: Irinotecan |
| MOFOX | Experimental | Modufolin in combination with 5-Fluorouracil and Oxaliplatin according to mFOLFOX-6 regime Receives: Drug: Modufolin (arfolitixorin); Drug: Fluorouracil; Drug: Oxaliplatin |
| MOFOX / Bevacizumab | Experimental | Modufolin in combination with 5-Fluorouracil, Oxaliplatin and Bevacizumab Receives: Drug: Modufolin (arfolitixorin); Drug: Fluorouracil; Drug: Oxaliplatin; Drug: Bevacizumab |
| MOFIRI | Experimental | Modufolin in combination with 5-Fluorouracil and Irinotecan Receives: Drug: Modufolin (arfolitixorin); Drug: Fluorouracil; Drug: Irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: The patients will be followed during 4 cycles of treatment (8 weeks).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2014 (estimated)
- Study startSep 2014
- Primary completion30 Jan 2020
- Study completion30 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Colorectal NeoplasmStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 105 participants (actual)
Sponsor and investigators
- Lead sponsor
- Isofol Medical AB
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Göran Carlsson, MD, Principal investigator, Sahlgrenska University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02244632
- Sponsor's protocol ID
- ISO-CC-005
- Other IDs
- 2014-001862-84, 2014
- Status last verified
- Sep 2020
- First submitted
- 17 Sep 2014
- Last updated
- 9 Sep 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 36183444Taflin 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.
PubMed 33099678
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02244632
- Acronym / sponsor ID
- ISO-CC-005
- Conditions
- Colorectal Neoplasm
- Keywords
- Colorectal cancer, Colorectal carcinoma, Colorectal tumors, Intestinal Neoplasm, Gastrointestinal Neoplasm, Gastrointestinal disease, 5,10-methylenetetrahydrofolate, Tetrahydrofolates
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 105 participants (actual)
- Lead sponsor
- Isofol Medical ABIndustry (pharma, biotech, devices)
- Study start
- Sep 2014 (actual)
- Primary completion
- 30 Jan 2020 (actual)
- Study completion
- 30 Jan 2020 (actual)
- First posted
- 19 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Modufolin / Nordic FLV | Experimental | Drug: Modufolin (arfolitixorin), Drug: FluorouracilModufolin in combination with 5-Fluorouracil only. |
| Modufolin / Nordic FLOX | Experimental | Drug: Modufolin (arfolitixorin), Drug: Fluorouracil, Drug: OxaliplatinModufolin in combination with 5-Fluorouracil and Oxaliplatin according to Nordic FLOX regime |
| Modufolin / Nordic FLIRI | Experimental | Drug: Modufolin (arfolitixorin), Drug: Fluorouracil, Drug: IrinotecanModufolin in combination with 5-Fluorouracil and Irinotecan. |
| MOFOX | Experimental | Drug: Modufolin (arfolitixorin), Drug: Fluorouracil, Drug: OxaliplatinModufolin in combination with 5-Fluorouracil and Oxaliplatin according to mFOLFOX-6 regime |
| MOFOX / Bevacizumab | Experimental | Drug: Modufolin (arfolitixorin), Drug: Fluorouracil, Drug: Oxaliplatin, Drug: BevacizumabModufolin in combination with 5-Fluorouracil, Oxaliplatin and Bevacizumab |
| MOFIRI | Experimental | Drug: Modufolin (arfolitixorin), Drug: Fluorouracil, Drug: IrinotecanModufolin in combination with 5-Fluorouracil and Irinotecan |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Advanced metastatic colorectal (Stage IV) cancer verified by biopsy
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Modufolin (arfolitixorin)Also: [6R] 5,10-methylenetetrahydrofolate, 6R-MTHF, 6R-methylene THF, ISO-901IV injection every second week for 8 weeks. | Drug | MOFIRI, MOFOX, MOFOX / Bevacizumab, Modufolin / Nordic FLIRI, Modufolin / Nordic FLOX, Modufolin / Nordic FLV |
| FluorouracilAlso: 5-FU, 5-Flourouacil, 5-Fluoro-1H,3H-pyrimidine-2,4-dione, AdrucilIV injection every second week for 8 weeks. | Drug | MOFIRI, MOFOX, MOFOX / Bevacizumab, Modufolin / Nordic FLIRI, Modufolin / Nordic FLOX, Modufolin / Nordic FLV |
| OxaliplatinAlso: Eloxatin, [(1R,2R)-cyclohexane-1,2-diamine](ethanedioato-O,O')platinum(II), Olatin, OxamedIV infusion every second week for 8 weeks. | Drug | MOFOX, MOFOX / Bevacizumab, Modufolin / Nordic FLOX |
| IrinotecanAlso: (+)-(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, NamedicaIV infusion every second week for 8 weeks. | Drug | MOFIRI, Modufolin / Nordic FLIRI |
| BevacizumabAlso: AvastinIV infusion every second week for 8 weeks. | Drug | MOFOX / Bevacizumab |
Primary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2020.
- Derived from this study: PubMed 36183444Carlsson 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.
- Derived from this study: PubMed 33099678Taflin 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Göran Carlsson, MD principal investigator
Sahlgrenska University Hospital
10 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Modufolin (arfolitixorin), Fluorouracil and Oxaliplatin in people with Colorectal Neoplasm, run by Isofol Medical AB at 10 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Greece, Norway, Sweden, Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02244632, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2020.