PK/PD Investigation of Modufolin® in Plasma, Tumor and Adjacent Mucosa in Patients With Colon Cancer

This study has been completed.
Information provided by (Responsible Party):
Isofol Medical AB Identifier:
First received: September 5, 2012
Last updated: February 16, 2016
Last verified: February 2016
The purpose of this study is to compare the concentration of [6R] 5,10-methylene-THF, 5-formyl-THF, 5-methyl-THF and THF in the tumor, in adjacent mucosa and in plasma in patients with colon cancer receiving two different does of Modufolin® and Levoleucovorin (Isovorin®) respectively (60 and 200 mg/m2).

Condition Intervention Phase
Colonic Neoplasms
Drug: [6R] 5,10-methylenetetrahydrofolate
Drug: Levoleucovorin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
Official Title: A Single-Blind, Randomized Phase I/II Study of Pharmacokinetic and Pharmacodynamic Investigation of Modufolin® (60 or 200 mg/m2) Compared to Levoleucovorin (60 or 200 mg/m2) in Tumor, Adjacent Mucosa and Plasma for Patients With Colon Cancer

Resource links provided by NLM:

Further study details as provided by Isofol Medical AB:

Primary Outcome Measures:
  • Comparison of Folate Concentration in Tumor Tissue and Adjacent Mucosa Between Treatment Arms. [ Time Frame: Sample taken Day 1 (Day of surgery). ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Difference in Pharmacokinetic Parameters of [6R] 5,10- Methylene-THF, 5-formyl-THF, 5-methyl-THF and THF Calculated From Plasma Concentration [ Time Frame: Samples taken on Screening visit, Day 1 and Day 2. ] [ Designated as safety issue: No ]
  • Adverse Events and Laboratory Measurements; Haematology, Clinical Chemistry and Urinalysis. [ Time Frame: Screening visit until end of study, Day 5 ] [ Designated as safety issue: Yes ]
  • Gene Expression in Tumor and Mucosa. [ Time Frame: Sample taken Day 1 (Day of Surgery) ] [ Designated as safety issue: No ]
  • Homocystein and Serum Folate Levels. [ Time Frame: Samples taken at Screening visit, Day 2 and End of Study (Day 5) ] [ Designated as safety issue: No ]

Enrollment: 32
Study Start Date: September 2012
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Levoleucovorin 200 mg/m2 Drug: Levoleucovorin
i.v. bolus injection
Other Name: Isovorin®
Active Comparator: Levoleucovorin 60 mg/m2 Drug: Levoleucovorin
i.v. bolus injection
Other Name: Isovorin®
Experimental: 6R-MTHF 200 mg/m2 Drug: [6R] 5,10-methylenetetrahydrofolate
i.v. bolus injection
Other Names:
  • Modufolin®
  • 6R-MTHF
  • ISO-901
Experimental: 6R-MTHF 60 mg/m2 Drug: [6R] 5,10-methylenetetrahydrofolate
i.v. bolus injection
Other Names:
  • Modufolin®
  • 6R-MTHF
  • ISO-901


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients must have operable colon cancer that is amenable to curative surgery.
  2. Performance status of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG).
  3. Patients without contra indications for undergoing surgery.
  4. For women: Must be surgically sterile, postmenopausal, or compliant with a contraceptive regimen during and for 3 months after treatment; must have a negative serum or urine pregnancy test (within 7 days before enrolment) and must not be lactating.
  5. For men: Must be surgically sterile or compliant with a contraceptive regimen during and for 3 months after treatment.
  6. Patients must sign an informed consent document.
  7. Patient legally competent and able to communicate effectively with the study personnel as judged by the investigator.
  8. Patient likely to co-operate during the study.
  9. Patients must be at least 18 years of age.

Exclusion Criteria:

  1. Concurrent administration of any other anti-tumor therapy.
  2. Treatment within the last 30 days with a drug/device that has not received regulatory approval for any indication at the time of study entry.
  3. Any intake of medication which could influence homocysteine, folate, and vitamin B12 status, within 30 days of surgery
  4. Serious concomitant systemic disorders (e.g., active infection including HIV, cardiac disease) that in the opinion of the investigator would compromise the patient's ability to complete the study.
  5. Are pregnant or breast-feeding.
  6. Second primary malignancy that is clinically detectable at the time of consideration for study enrollment.
  7. History of significant neurological or mental disorder, including seizures or dementia.
  8. Presence of clinically relevant (i.e., detectable by physical examination) third-space fluid collection (e.g., ascites, pleural effusion) that cannot be controlled by drainage or other procedures prior to study entry.
  9. Inability or unwillingness to be given Modufolin® or Levoleucovorin (Isovorin®).
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Please refer to this study by its identifier: NCT01681472

Sahlgrenska University Hospital
Gothenburg, Sweden, 461 85
Sponsors and Collaborators
Isofol Medical AB
Principal Investigator: Kristoffer Derwinger, MD PhD Sahlgrenska University Hospital, Sweden
  More Information

Responsible Party: Isofol Medical AB Identifier: NCT01681472     History of Changes
Other Study ID Numbers: ISO-CC-002  2012-000522-22 
Study First Received: September 5, 2012
Results First Received: May 21, 2015
Last Updated: February 16, 2016
Health Authority: Sweden: Regional Ethical Review Board
Sweden: Medical Products Agency
Sweden: Swedish Data Inspection Board

Keywords provided by Isofol Medical AB:
Colon cancer
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Gastrointestinal Diseases
Therapeutic Uses

Additional relevant MeSH terms:
Colonic Neoplasms
Colonic Diseases
Colorectal Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms by Site
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Vitamin B Complex
Vitamins processed this record on May 03, 2016