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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Isofol Medical AB
ClinicalTrials.gov Identifier:
NCT01681472
First received: September 5, 2012
Last updated: March 5, 2014
Last verified: March 2014
  Purpose

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® Compared to Levoleucovorin 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:
  • To explore if there is a 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 ]
  • To study safety in terms of 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 ]
  • To study gene expression in tumor and mucosa. [ Time Frame: Sample taken Day 1 (Day of Surgery) ] [ Designated as safety issue: No ]
  • To study 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
  • [6R] 5,10-methylenetetrahydrofolate
Experimental: 6R-MTHF 60 mg/m2 Drug: [6R] 5,10-methylenetetrahydrofolate
i.v. bolus injection
Other Names:
  • Modufolin®
  • 6R-MTHF
  • ISO-901
  • [6R] 5,10-methylenetetrahydrofolate

  Eligibility

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

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®).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01681472

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

No publications provided

Responsible Party: Isofol Medical AB
ClinicalTrials.gov Identifier: NCT01681472     History of Changes
Other Study ID Numbers: ISO-CC-002, 2012-000522-22
Study First Received: September 5, 2012
Last Updated: March 5, 2014
Health Authority: Sweden: Regional Ethical Review Board
Sweden: Medical Products Agency
Sweden: Swedish Data Inspection Board

Keywords provided by Isofol Medical AB:
Colon cancer
5,10-methylenetetrahydrofolate
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Gastrointestinal Diseases
Therapeutic Uses
Pharmacokinetics
Pharmacodynamics

Additional relevant MeSH terms:
Neoplasms
Colonic Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Levoleucovorin
Leucovorin
Tetrahydrofolates
Antidotes
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on April 17, 2014