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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Colorectal Neoplasm

Intervention / Treatment
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* Drug: Modufolin (arfolitixorin)
* Drug: Fluorouracil
* Drug: Oxaliplatin
* Drug: Irinotecan
* Drug: Bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced metastatic colorectal (Stage IV) cancer verified by biopsy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Modufolin / Nordic FLV<br>Modufolin in combination with 5-Fluorouracil only. | Drug: Modufolin (arfolitixorin)<br>* IV injection every second week for 8 weeks.<br>* Other names: arfolitixorin;Drug: Fluorouracil<br>* IV injection every second week for 8 weeks.<br>* Other names: Adrucil;|
| Experimental: Modufolin / Nordic FLOX<br>Modufolin in combination with 5-Fluorouracil and Oxaliplatin according to Nordic FLOX regime | Drug: Modufolin (arfolitixorin)<br>* IV injection every second week for 8 weeks.<br>* Other names: arfolitixorin;Drug: Fluorouracil<br>* IV injection every second week for 8 weeks.<br>* Other names: Adrucil;Drug: Oxaliplatin<br>* IV infusion every second week for 8 weeks.<br>* Other names: Oxitropic;|
| Experimental: Modufolin / Nordic FLIRI<br>Modufolin in combination with 5-Fluorouracil and Irinotecan. | Drug: Modufolin (arfolitixorin)<br>* IV injection every second week for 8 weeks.<br>* Other names: arfolitixorin;Drug: Fluorouracil<br>* IV injection every second week for 8 weeks.<br>* Other names: Adrucil;Drug: Irinotecan<br>* IV infusion every second week for 8 weeks.<br>* Other names: Namedica;|
| Experimental: MOFOX<br>Modufolin in combination with 5-Fluorouracil and Oxaliplatin according to mFOLFOX-6 regime | Drug: Modufolin (arfolitixorin)<br>* IV injection every second week for 8 weeks.<br>* Other names: arfolitixorin;Drug: Fluorouracil<br>* IV injection every second week for 8 weeks.<br>* Other names: Adrucil;Drug: Oxaliplatin<br>* IV infusion every second week for 8 weeks.<br>* Other names: Oxitropic;|
| Experimental: MOFOX / Bevacizumab<br>Modufolin in combination with 5-Fluorouracil, Oxaliplatin and Bevacizumab | Drug: Modufolin (arfolitixorin)<br>* IV injection every second week for 8 weeks.<br>* Other names: arfolitixorin;Drug: Fluorouracil<br>* IV injection every second week for 8 weeks.<br>* Other names: Adrucil;Drug: Oxaliplatin<br>* IV infusion every second week for 8 weeks.<br>* Other names: Oxitropic;Drug: Bevacizumab<br>* IV infusion every second week for 8 weeks.<br>* Other names: Avastin;|
| Experimental: MOFIRI<br>Modufolin in combination with 5-Fluorouracil and Irinotecan | Drug: Modufolin (arfolitixorin)<br>* IV injection every second week for 8 weeks.<br>* Other names: arfolitixorin;Drug: Fluorouracil<br>* IV injection every second week for 8 weeks.<br>* Other names: Adrucil;Drug: Irinotecan<br>* IV infusion every second week for 8 weeks.<br>* Other names: Namedica;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety assessments, Colorectal cancer, Colorectal carcinoma, Colorectal tumors, Intestinal Neoplasm, Gastrointestinal Neoplasm, Gastrointestinal disease, 5,10-methylenetetrahydrofolate, Tetrahydrofolates, Therapeutic uses, Pharmacokinetics, Pharmacodynamics