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Trial record 12 of 4159 for:    colon cancer AND Intestinal Neoplasms

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

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ClinicalTrials.gov Identifier: NCT01681472
Recruitment Status : Completed
First Posted : September 10, 2012
Results First Posted : July 17, 2015
Last Update Posted : July 10, 2019
Sponsor:
Information provided by (Responsible Party):
Isofol Medical AB

Brief Summary:
The purpose of this study is to compare the concentration of four different metabolites in the tumor, in adjacent mucosa and in plasma in patients with colon cancer receiving two different doses of Modufolin® and Levoleucovorin (Isovorin®), respectively (60 and 200 mg/m2).

Condition or disease Intervention/treatment Phase
Colonic Neoplasms Drug: 6R-MTHF 200 mg/m2 Drug: Levoleucovorin 200 mg/m2 Drug: 6R-MTHF 60 mg/m2 Drug: Levoleucovorin 60 mg/m2 Phase 1 Phase 2

Detailed Description:
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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Primary Purpose: Treatment
Official Title: A Single-Blind, Randomized Phase I/II Study of Pharmacokinetic and Pharmacodynamic Investigation of Modufolin® (60 or 200mg/m2) Compared to Levoleucovorin (60 or 200mg/m2) in Tumor, Adjacent Mucosa and Plasma for Patients With Colon Cancer
Study Start Date : September 2012
Actual Primary Completion Date : August 2013
Actual Study Completion Date : August 2013

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Levoleucovorin 200 mg/m2
One i.v. bolus injection of study drug after the patient has been anaesthetized.
Drug: Levoleucovorin 200 mg/m2
i.v. bolus injection
Other Name: Isovorin®

Active Comparator: Levoleucovorin 60 mg/m2
One i.v. bolus injection of study drug after the patient has been anaesthetized.
Drug: Levoleucovorin 60 mg/m2
i.v. bolus injection
Other Name: Isovorin®

Experimental: 6R-MTHF 200 mg/m2
One i.v. bolus injection of study drug after the patient has been anaesthetized.
Drug: 6R-MTHF 200 mg/m2
i.v. bolus injection
Other Names:
  • Modufolin®
  • ISO-901
  • [6R] 5,10-methylenetetrahydrofolate

Experimental: 6R-MTHF 60 mg/m2
One i.v. bolus injection of study drug after the patient has been anaesthetized.
Drug: 6R-MTHF 60 mg/m2
i.v. bolus injection
Other Names:
  • Modufolin®
  • ISO-901
  • [6R] 5,10-methylenetetrahydrofolate




Primary Outcome Measures :
  1. Concentration of [6R]-5,10-methylene-THF in Tumor Tissue [ Time Frame: Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration ]
    Comparison of concentration of the active substance in Modufolin: [6R]-5,10-methylene-THF in tumor tissue after the different treatments.

  2. Concentration of [6R]-5,10-methylene-THF in Adjacent Mucosa Tissue [ Time Frame: Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration ]
    Comparison of concentration of the active substance in Modufolin: [6R]-5,10-methylene-THF in mucosa adjacent to the tumor after the different treatments.

  3. Concentration of [6S]-5-THF in Tumor Tissue [ Time Frame: Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration ]
    Comparison of concentration of the metabolite [6S]-5-THF in tumor after the different treatments.

  4. Concentration of [6S]-5-THF in Adjacent Mucosa Tissue [ Time Frame: Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration ]
    Comparison of concentration of the metabolite [6S]-5-THF in mucosa adjacent to the tumor after the different treatments.

  5. Concentration of [6S]-5-methyl-THF in Tumor Tissue [ Time Frame: Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration ]
    Comparison of concentration of the metabolite [6S]-5-methyl-THF in tumor after the different treatments.

  6. Concentration of [6S]-5-methyl-THF in Adjacent Mucosa Tissue [ Time Frame: Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration ]
    Comparison of concentration of the metabolite [6S]-5-methyl-THF in mucosa adjacent to the tumor after the different treatments.

  7. Concentration of [6S]-5-formyl-THF in Tumor Tissue [ Time Frame: Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration ]
    Comparison of concentration of the metabolite [6S]-5-formyl-THF in tumor after the different treatments.

  8. Concentration of [6S]-5-formyl-THF in Adjacent Mucosa Tissue [ Time Frame: Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration ]
    Comparison of concentration of the metabolite [6S]-5-formyl-THF in mucosa adjacent to the tumor after the different treatments.


Secondary Outcome Measures :
  1. AUC(0-2h) of [6R]-5,10-methylene-THF [ Time Frame: Samples taken Day 1 (Day of surgery) ]
    Area under the plasma concentration versus time curve from time 0 to 2 hours, for the active substance in Modufolin: [6R]-5,10-methylene-THF

  2. AUC(0-2h) of [6S]-5-THF [ Time Frame: Samples taken Day 1 (Day of surgery) ]
    Area under the plasma concentration versus time curve from time 0 to 2 hours, for the metabolite [6S]-5-THF

  3. AUC(0-2h) of [6S]-5-methyl-THF [ Time Frame: Samples taken Day 1 (Day of surgery) ]
    Area under the plasma concentration versus time curve from time 0 to 2 hours, for the metabolite: [6S]-5-methyl-THF

  4. AUC(0-2h) of [6SR]-5-formyl-THF [ Time Frame: Samples taken Day 1 (Day of surgery) ]
    Area under the plasma concentration versus time curve from time 0 to 2 hours, for the metabolite [6S]-5-formyl-THF

  5. AUC(Last) of [6R]-5,10-methylene-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Area under the plasma concentration versus time curve, from time 0 to the last time point, for the active substance in Modufolin: [6R]-5,10-methylene-THF

  6. AUC(Last) of [6S]-5-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Area under the plasma concentration versus time curve, from time 0 to the last time point, for the metabolite [6S]-5-THF

  7. AUC(Last) of [6S]-5-methyl-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Area under the plasma concentration versus time curve, from time 0 to the last time point, for the metabolite [6S]-5-methyl-THF

  8. AUC(Last) of [6S]-5-formyl-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Area under the plasma concentration versus time curve, from time 0 to the last time point, for the metabolite [6S]-5-formyl-THF

  9. Cmax of [6R]-5,10-methylene-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Maximum concentration (Cmax) in plasma of the active substance in Modufolin: [6R]-5,10-methylene-THF

  10. Cmax of [6S]-5-THF in Plasma [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Maximum concentration (Cmax) in plasma of the metabolite [6S]-5-THF

  11. Cmax of [6S]-5-methyl-THF in Plasma [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Maximum concentration (Cmax) in plasma of the metabolite [6S]-5-methyl-THF

  12. Cmax of [6S]-5-formyl-THF in Plasma [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Maximum concentration (Cmax) in plasma of the active substance in Modufolin: [6R] 5,10- methylene-THF and the metabolites: [6S]-5-THF, [6S]-5-methyl-THF, and [6S]-5-formyl-THF

  13. Tmax of [6R]-5,10-methylene-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Timepoint (tmax) when Cmax in plasma occurs of the active substance in Modufolin: [6R]-5,10-methylene-THF

  14. Tmax of [6S]-5-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Timepoint (tmax) when Cmax in plasma occurs for the metabolite [6S]-5-THF

  15. Tmax of [6S]-5-methyl-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Timepoint (tmax) when Cmax in plasma occurs for the metabolite [6S]-5-methyl-THF

  16. Tmax of [6S]-5-formyl-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Timepoint (tmax) when Cmax in plasma occurs for the metabolite [6S]-5-formyl-THF

  17. T(1/2) of [6R]-5,10-methylene-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Terminal plasma elimination half-life time for the active substance in Modufolin: [6R]-5,10-methylene-THF

  18. T(1/2) of [6S]-5-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Terminal plasma elimination half-life time for the metabolite [6S]-5-THF

  19. T(1/2) of [6S]-5-methyl-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Terminal plasma elimination half-life time for the metabolite [6S]-5-methyl-THF

  20. T(1/2) of [6S]-5-formyl-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Terminal plasma elimination half-life time for the metabolite [6S]-5-formyl-THF

  21. T(Last) of [6R]-5,10-methylene-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    The time-point for the last measurable concentration of the active substance in Modufolin: [6R]-5,10-methylene-THF

  22. T(Last) of [6S]-5-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    The time-point for the last measurable concentration for the metabolite [6S]-5-TH in plasma

  23. T(Last) of [6S]-5-methyl-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    The time-point for the last measurable concentration for the metabolite [6S]-5-methyl-THF in plasma

  24. T(Last) of [6S]-5-formyl-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    The time-point for the last measurable concentration for the metabolite [6S]-5-formyl-THF in plasma

  25. Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6R]-5,10-methylene-THF [ Time Frame: Samples taken Day 1 (Day of surgery) ]
    Correlation between the exposure of [6R]-5,10-methylene-THF following 2 hours after dosing (AUC[0-2h]) and the concentration of [6R]-5,10-methylene-THF in the tumor or adjacent mucosa at surgery.

  26. Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6S]-5-THF [ Time Frame: Samples taken Day 1 (Day of surgery) ]
    Correlation between the exposure of [6S]-5-THF following 2 hours after dosing (AUC[0-2h]) and the concentration of [6S]-5-THF in the tumor or adjacent mucosa at surgery.

  27. Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6S]-5-methyl-THF [ Time Frame: Samples taken Day 1 (Day of surgery) ]
    Correlation between the exposure of [6S]-5-methyl-THF following 2 hours after dosing (AUC[0-2h]) and the concentration of [6S]-5-methyl-THF in the tumor or adjacent mucosa at surgery.

  28. Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6S]-5-formyl-THF [ Time Frame: Samples taken Day 1 (Day of surgery) ]
    Correlation between the exposure of [6S]-5-formyl-THF following 2 hours after dosing (AUC[0-2h]) and the concentration of [6S]-5-formyl-THF in the tumor or adjacent mucosa at surgery.

  29. Gene Expression Ratios (Mucosa:Tumor) [ Time Frame: Sample taken Day 1 (Day of Surgery) ]
    Concentration of different genes involved in folate transport and metabolism were analysed in both tumor and adjacent mucosa. The concentration in mucosa was divided by the concentration in tumor. A value above 1 indicate that the gene expression was higher in mucosa than in tumor and a value below 1 that the gene expression was higher in tumor than in mucosa.

  30. Correlation of Gene Expression in Tumor and Adjacent Mucosa [ Time Frame: Sample taken Day 1 (Day of Surgery) ]
    Concentration of the gene expression was analysed in both tumor and adjacent mucosa. The presence of any correlation between the results (i.e., concentration of the gene expression in tumor versus adjacent mucosa) was evaluated for each treatment. No evaluation was done between treatments.

  31. Homocystein Concentration [ Time Frame: Samples taken at Screening visit, Day 2, and End of Study (Day 5) ]
    Blood samples for folate biomarker (homocystein) analysis were collected at Screening, Day 2, and Day 5 (End of study visit).

  32. S-Folate Concentration [ Time Frame: Samples taken at Screening visit, Day 2 and End of Study (Day 5) ]
    Blood samples for folate biomarker (S-folate) analysis were collected at Screening, Day 2 and Day 5 (End of study visit).

  33. Change in Homocystein Concentration From Screening [ Time Frame: Samples taken at Screening visit, Day 2 and End of Study (Day 5) ]

    Blood samples for folate biomarker (homocystein) analysis were collected at Screening, Day 2 and Day 5 (End of study visit). Changes from screening to later visits were counted.

    The criteria for assessment categories "normal", "low" and "high" were based on the reference ranges for plasma-Homocystein as follows: "low" <4,7 mcmol/L; "normal" => 4,7 and <=16 mcmol/L; "high" >16 mcmol/L. Values were applicable for both male and female adults.


  34. Change in S-Folate Concentration From Screening [ Time Frame: Samples taken at Screening visit, Day 2 and End of Study (Day 5) ]
    Blood samples for folate biomarker (S-folate) analysis were collected at Screening, Day 2 and Day 5 (End of study visit). Changes from screening to later visits were counted.

  35. Number of AEs Per Severity [ Time Frame: Screening visit until end of study, Day 5 ]
    Number of reported AEs per treatment with respect to severity



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Main Inclusion Criteria:

  • Operable colon cancer amenable to curative surgery.
  • Performance status of 0 to 1
  • Informed consent form
  • Patients must be at least 18 years of age.

Main Exclusion Criteria:

  • Any concurrent other anti-tumor therapy
  • Any prohibited concomitant medication within 30 days of surgery
  • Pregnancy or breast-feeding.
  • Second primary malignancy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01681472


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

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Responsible Party: Isofol Medical AB
ClinicalTrials.gov Identifier: NCT01681472     History of Changes
Other Study ID Numbers: ISO-CC-002
2012-000522-22 ( EudraCT Number )
First Posted: September 10, 2012    Key Record Dates
Results First Posted: July 17, 2015
Last Update Posted: July 10, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

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