Back to resultsPK/PD Investigation of Modufolin (Arfolitixorin) in Plasma, Tumor and Adjacent Mucosa Adjacent Mucosa in Patients With Colon Cancer
Primary Purpose
Colonic Neoplasms
Status
Completed
Phase
Phase 1
Locations
Sweden
Study Type
Interventional
Intervention
6R-MTHF (arfolitixorin) 200 mg/m2
Levoleucovorin 200 mg/m2
6R-MTHF (arfolitixorin) 60 mg/m2
Levoleucovorin 60 mg/m2
Sponsored by
About this trial
This is an interventional treatment trial for Colonic Neoplasms focused on measuring Colon cancer, 5,10-methylenetetrahydrofolate, Rectal Neoplasms, Colorectal Neoplasms, Intestinal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms, Gastrointestinal Diseases, Therapeutic Uses, Pharmacokinetics, Pharmacodynamics
Eligibility 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
Sites / Locations
- Sahlgrenska University Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Active Comparator
Active Comparator
Experimental
Experimental
Arm Label
Levoleucovorin 200 mg/m2
Levoleucovorin 60 mg/m2
6R-MTHF 200 mg/m2
6R-MTHF 60 mg/m2
Arm Description
One i.v. bolus injection of study drug after the patient has been anaesthetized.
One i.v. bolus injection of study drug after the patient has been anaesthetized.
One i.v. bolus injection of study drug after the patient has been anaesthetized.
One i.v. bolus injection of study drug after the patient has been anaesthetized.
Outcomes
Primary Outcome Measures
Concentration of [6R]-5,10-methylene-THF in Tumor Tissue
Comparison of concentration of the active substance in Modufolin: [6R]-5,10-methylene-THF in tumor tissue after the different treatments.
Concentration of [6R]-5,10-methylene-THF in Adjacent Mucosa Tissue
Comparison of concentration of the active substance in Modufolin: [6R]-5,10-methylene-THF in mucosa adjacent to the tumor after the different treatments.
Concentration of [6S]-5-THF in Tumor Tissue
Comparison of concentration of the metabolite [6S]-5-THF in tumor after the different treatments.
Concentration of [6S]-5-THF in Adjacent Mucosa Tissue
Comparison of concentration of the metabolite [6S]-5-THF in mucosa adjacent to the tumor after the different treatments.
Concentration of [6S]-5-methyl-THF in Tumor Tissue
Comparison of concentration of the metabolite [6S]-5-methyl-THF in tumor after the different treatments.
Concentration of [6S]-5-methyl-THF in Adjacent Mucosa Tissue
Comparison of concentration of the metabolite [6S]-5-methyl-THF in mucosa adjacent to the tumor after the different treatments.
Concentration of [6S]-5-formyl-THF in Tumor Tissue
Comparison of concentration of the metabolite [6S]-5-formyl-THF in tumor after the different treatments.
Concentration of [6S]-5-formyl-THF in Adjacent Mucosa Tissue
Comparison of concentration of the metabolite [6S]-5-formyl-THF in mucosa adjacent to the tumor after the different treatments.
Secondary Outcome Measures
AUC(0-2h) of [6R]-5,10-methylene-THF
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
AUC(0-2h) of [6S]-5-THF
Area under the plasma concentration versus time curve from time 0 to 2 hours, for the metabolite [6S]-5-THF
AUC(0-2h) of [6S]-5-methyl-THF
Area under the plasma concentration versus time curve from time 0 to 2 hours, for the metabolite: [6S]-5-methyl-THF
AUC(0-2h) of [6SR]-5-formyl-THF
Area under the plasma concentration versus time curve from time 0 to 2 hours, for the metabolite [6S]-5-formyl-THF
AUC(Last) of [6R]-5,10-methylene-THF
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
AUC(Last) of [6S]-5-THF
Area under the plasma concentration versus time curve, from time 0 to the last time point, for the metabolite [6S]-5-THF
AUC(Last) of [6S]-5-methyl-THF
Area under the plasma concentration versus time curve, from time 0 to the last time point, for the metabolite [6S]-5-methyl-THF
AUC(Last) of [6S]-5-formyl-THF
Area under the plasma concentration versus time curve, from time 0 to the last time point, for the metabolite [6S]-5-formyl-THF
Cmax of [6R]-5,10-methylene-THF
Maximum concentration (Cmax) in plasma of the active substance in Modufolin: [6R]-5,10-methylene-THF
Cmax of [6S]-5-THF in Plasma
Maximum concentration (Cmax) in plasma of the metabolite [6S]-5-THF
Cmax of [6S]-5-methyl-THF in Plasma
Maximum concentration (Cmax) in plasma of the metabolite [6S]-5-methyl-THF
Cmax of [6S]-5-formyl-THF in Plasma
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
Tmax of [6R]-5,10-methylene-THF
Timepoint (tmax) when Cmax in plasma occurs of the active substance in Modufolin: [6R]-5,10-methylene-THF
Tmax of [6S]-5-THF
Timepoint (tmax) when Cmax in plasma occurs for the metabolite [6S]-5-THF
Tmax of [6S]-5-methyl-THF
Timepoint (tmax) when Cmax in plasma occurs for the metabolite [6S]-5-methyl-THF
Tmax of [6S]-5-formyl-THF
Timepoint (tmax) when Cmax in plasma occurs for the metabolite [6S]-5-formyl-THF
T(1/2) of [6R]-5,10-methylene-THF
Terminal plasma elimination half-life time for the active substance in Modufolin: [6R]-5,10-methylene-THF
T(1/2) of [6S]-5-THF
Terminal plasma elimination half-life time for the metabolite [6S]-5-THF
T(1/2) of [6S]-5-methyl-THF
Terminal plasma elimination half-life time for the metabolite [6S]-5-methyl-THF
T(1/2) of [6S]-5-formyl-THF
Terminal plasma elimination half-life time for the metabolite [6S]-5-formyl-THF
T(Last) of [6R]-5,10-methylene-THF
The time-point for the last measurable concentration of the active substance in Modufolin: [6R]-5,10-methylene-THF
T(Last) of [6S]-5-THF
The time-point for the last measurable concentration for the metabolite [6S]-5-TH in plasma
T(Last) of [6S]-5-methyl-THF
The time-point for the last measurable concentration for the metabolite [6S]-5-methyl-THF in plasma
T(Last) of [6S]-5-formyl-THF
The time-point for the last measurable concentration for the metabolite [6S]-5-formyl-THF in plasma
Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6R]-5,10-methylene-THF
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.
Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6S]-5-THF
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.
Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6S]-5-methyl-THF
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.
Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6S]-5-formyl-THF
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.
Gene Expression Ratios (Mucosa:Tumor)
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.
Correlation of Gene Expression in Tumor and Adjacent Mucosa
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.
Homocystein Concentration
Blood samples for folate biomarker (homocystein) analysis were collected at Screening, Day 2, and Day 5 (End of study visit).
S-Folate Concentration
Blood samples for folate biomarker (S-folate) analysis were collected at Screening, Day 2 and Day 5 (End of study visit).
Change in Homocystein Concentration From Screening
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.
Change in S-Folate Concentration From Screening
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.
Number of AEs Per Severity
Number of reported AEs per treatment with respect to severity
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01681472
Brief Title
PK/PD Investigation of Modufolin (Arfolitixorin) in Plasma, Tumor and Adjacent Mucosa Adjacent Mucosa in Patients With Colon Cancer
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 Type
Interventional
2. Study Status
Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
September 2012 (undefined)
Primary Completion Date
August 2013 (Actual)
Study Completion Date
August 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Isofol Medical AB
4. Oversight
Data Monitoring Committee
No
5. Study Description
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 (arfolitixorin) and Levoleucovorin (Isovorin®), respectively (60 and 200 mg/m2).
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colonic Neoplasms
Keywords
Colon cancer, 5,10-methylenetetrahydrofolate, Rectal Neoplasms, Colorectal Neoplasms, Intestinal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms, Gastrointestinal Diseases, Therapeutic Uses, Pharmacokinetics, Pharmacodynamics
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
Investigator
Allocation
Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Levoleucovorin 200 mg/m2
Arm Type
Active Comparator
Arm Description
One i.v. bolus injection of study drug after the patient has been anaesthetized.
Arm Title
Levoleucovorin 60 mg/m2
Arm Type
Active Comparator
Arm Description
One i.v. bolus injection of study drug after the patient has been anaesthetized.
Arm Title
6R-MTHF 200 mg/m2
Arm Type
Experimental
Arm Description
One i.v. bolus injection of study drug after the patient has been anaesthetized.
Arm Title
6R-MTHF 60 mg/m2
Arm Type
Experimental
Arm Description
One i.v. bolus injection of study drug after the patient has been anaesthetized.
Intervention Type
Drug
Intervention Name(s)
6R-MTHF (arfolitixorin) 200 mg/m2
Other Intervention Name(s)
Modufolin®, ISO-901, [6R] 5,10-methylenetetrahydrofolate, arfolitixorin
Intervention Description
i.v. bolus injection
Intervention Type
Drug
Intervention Name(s)
Levoleucovorin 200 mg/m2
Other Intervention Name(s)
Isovorin®
Intervention Description
i.v. bolus injection
Intervention Type
Drug
Intervention Name(s)
6R-MTHF (arfolitixorin) 60 mg/m2
Other Intervention Name(s)
Modufolin®, ISO-901, [6R] 5,10-methylenetetrahydrofolate, arfolitixorin
Intervention Description
i.v. bolus injection
Intervention Type
Drug
Intervention Name(s)
Levoleucovorin 60 mg/m2
Other Intervention Name(s)
Isovorin®
Intervention Description
i.v. bolus injection
Primary Outcome Measure Information:
Title
Concentration of [6R]-5,10-methylene-THF in Tumor Tissue
Description
Comparison of concentration of the active substance in Modufolin: [6R]-5,10-methylene-THF in tumor tissue after the different treatments.
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
Title
Concentration of [6R]-5,10-methylene-THF in Adjacent Mucosa Tissue
Description
Comparison of concentration of the active substance in Modufolin: [6R]-5,10-methylene-THF in mucosa adjacent to the tumor after the different treatments.
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
Title
Concentration of [6S]-5-THF in Tumor Tissue
Description
Comparison of concentration of the metabolite [6S]-5-THF in tumor after the different treatments.
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
Title
Concentration of [6S]-5-THF in Adjacent Mucosa Tissue
Description
Comparison of concentration of the metabolite [6S]-5-THF in mucosa adjacent to the tumor after the different treatments.
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
Title
Concentration of [6S]-5-methyl-THF in Tumor Tissue
Description
Comparison of concentration of the metabolite [6S]-5-methyl-THF in tumor after the different treatments.
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
Title
Concentration of [6S]-5-methyl-THF in Adjacent Mucosa Tissue
Description
Comparison of concentration of the metabolite [6S]-5-methyl-THF in mucosa adjacent to the tumor after the different treatments.
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
Title
Concentration of [6S]-5-formyl-THF in Tumor Tissue
Description
Comparison of concentration of the metabolite [6S]-5-formyl-THF in tumor after the different treatments.
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
Title
Concentration of [6S]-5-formyl-THF in Adjacent Mucosa Tissue
Description
Comparison of concentration of the metabolite [6S]-5-formyl-THF in mucosa adjacent to the tumor after the different treatments.
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
Secondary Outcome Measure Information:
Title
AUC(0-2h) of [6R]-5,10-methylene-THF
Description
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
Time Frame
Samples taken Day 1 (Day of surgery)
Title
AUC(0-2h) of [6S]-5-THF
Description
Area under the plasma concentration versus time curve from time 0 to 2 hours, for the metabolite [6S]-5-THF
Time Frame
Samples taken Day 1 (Day of surgery)
Title
AUC(0-2h) of [6S]-5-methyl-THF
Description
Area under the plasma concentration versus time curve from time 0 to 2 hours, for the metabolite: [6S]-5-methyl-THF
Time Frame
Samples taken Day 1 (Day of surgery)
Title
AUC(0-2h) of [6SR]-5-formyl-THF
Description
Area under the plasma concentration versus time curve from time 0 to 2 hours, for the metabolite [6S]-5-formyl-THF
Time Frame
Samples taken Day 1 (Day of surgery)
Title
AUC(Last) of [6R]-5,10-methylene-THF
Description
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
Time Frame
Samples taken Day 1 (Day of surgery) and Day 2
Title
AUC(Last) of [6S]-5-THF
Description
Area under the plasma concentration versus time curve, from time 0 to the last time point, for the metabolite [6S]-5-THF
Time Frame
Samples taken Day 1 (Day of surgery) and Day 2
Title
AUC(Last) of [6S]-5-methyl-THF
Description
Area under the plasma concentration versus time curve, from time 0 to the last time point, for the metabolite [6S]-5-methyl-THF
Time Frame
Samples taken Day 1 (Day of surgery) and Day 2
Title
AUC(Last) of [6S]-5-formyl-THF
Description
Area under the plasma concentration versus time curve, from time 0 to the last time point, for the metabolite [6S]-5-formyl-THF
Time Frame
Samples taken Day 1 (Day of surgery) and Day 2
Title
Cmax of [6R]-5,10-methylene-THF
Description
Maximum concentration (Cmax) in plasma of the active substance in Modufolin: [6R]-5,10-methylene-THF
Time Frame
Samples taken Day 1 (Day of surgery) and Day 2
Title
Cmax of [6S]-5-THF in Plasma
Description
Maximum concentration (Cmax) in plasma of the metabolite [6S]-5-THF
Time Frame
Samples taken Day 1 (Day of surgery) and Day 2
Title
Cmax of [6S]-5-methyl-THF in Plasma
Description
Maximum concentration (Cmax) in plasma of the metabolite [6S]-5-methyl-THF
Time Frame
Samples taken Day 1 (Day of surgery) and Day 2
Title
Cmax of [6S]-5-formyl-THF in Plasma
Description
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
Time Frame
Samples taken Day 1 (Day of surgery) and Day 2
Title
Tmax of [6R]-5,10-methylene-THF
Description
Timepoint (tmax) when Cmax in plasma occurs of the active substance in Modufolin: [6R]-5,10-methylene-THF
Time Frame
Samples taken Day 1 (Day of surgery) and Day 2
Title
Tmax of [6S]-5-THF
Description
Timepoint (tmax) when Cmax in plasma occurs for the metabolite [6S]-5-THF
Time Frame
Samples taken Day 1 (Day of surgery) and Day 2
Title
Tmax of [6S]-5-methyl-THF
Description
Timepoint (tmax) when Cmax in plasma occurs for the metabolite [6S]-5-methyl-THF
Time Frame
Samples taken Day 1 (Day of surgery) and Day 2
Title
Tmax of [6S]-5-formyl-THF
Description
Timepoint (tmax) when Cmax in plasma occurs for the metabolite [6S]-5-formyl-THF
Time Frame
Samples taken Day 1 (Day of surgery) and Day 2
Title
T(1/2) of [6R]-5,10-methylene-THF
Description
Terminal plasma elimination half-life time for the active substance in Modufolin: [6R]-5,10-methylene-THF
Time Frame
Samples taken Day 1 (Day of surgery) and Day 2
Title
T(1/2) of [6S]-5-THF
Description
Terminal plasma elimination half-life time for the metabolite [6S]-5-THF
Time Frame
Samples taken Day 1 (Day of surgery) and Day 2
Title
T(1/2) of [6S]-5-methyl-THF
Description
Terminal plasma elimination half-life time for the metabolite [6S]-5-methyl-THF
Time Frame
Samples taken Day 1 (Day of surgery) and Day 2
Title
T(1/2) of [6S]-5-formyl-THF
Description
Terminal plasma elimination half-life time for the metabolite [6S]-5-formyl-THF
Time Frame
Samples taken Day 1 (Day of surgery) and Day 2
Title
T(Last) of [6R]-5,10-methylene-THF
Description
The time-point for the last measurable concentration of the active substance in Modufolin: [6R]-5,10-methylene-THF
Time Frame
Samples taken Day 1 (Day of surgery) and Day 2
Title
T(Last) of [6S]-5-THF
Description
The time-point for the last measurable concentration for the metabolite [6S]-5-TH in plasma
Time Frame
Samples taken Day 1 (Day of surgery) and Day 2
Title
T(Last) of [6S]-5-methyl-THF
Description
The time-point for the last measurable concentration for the metabolite [6S]-5-methyl-THF in plasma
Time Frame
Samples taken Day 1 (Day of surgery) and Day 2
Title
T(Last) of [6S]-5-formyl-THF
Description
The time-point for the last measurable concentration for the metabolite [6S]-5-formyl-THF in plasma
Time Frame
Samples taken Day 1 (Day of surgery) and Day 2
Title
Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6R]-5,10-methylene-THF
Description
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.
Time Frame
Samples taken Day 1 (Day of surgery)
Title
Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6S]-5-THF
Description
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.
Time Frame
Samples taken Day 1 (Day of surgery)
Title
Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6S]-5-methyl-THF
Description
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.
Time Frame
Samples taken Day 1 (Day of surgery)
Title
Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6S]-5-formyl-THF
Description
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.
Time Frame
Samples taken Day 1 (Day of surgery)
Title
Gene Expression Ratios (Mucosa:Tumor)
Description
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.
Time Frame
Sample taken Day 1 (Day of Surgery)
Title
Correlation of Gene Expression in Tumor and Adjacent Mucosa
Description
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.
Time Frame
Sample taken Day 1 (Day of Surgery)
Title
Homocystein Concentration
Description
Blood samples for folate biomarker (homocystein) analysis were collected at Screening, Day 2, and Day 5 (End of study visit).
Time Frame
Samples taken at Screening visit, Day 2, and End of Study (Day 5)
Title
S-Folate Concentration
Description
Blood samples for folate biomarker (S-folate) analysis were collected at Screening, Day 2 and Day 5 (End of study visit).
Time Frame
Samples taken at Screening visit, Day 2 and End of Study (Day 5)
Title
Change in Homocystein Concentration From Screening
Description
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.
Time Frame
Samples taken at Screening visit, Day 2 and End of Study (Day 5)
Title
Change in S-Folate Concentration From Screening
Description
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.
Time Frame
Samples taken at Screening visit, Day 2 and End of Study (Day 5)
Title
Number of AEs Per Severity
Description
Number of reported AEs per treatment with respect to severity
Time Frame
Screening visit until end of study, Day 5
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kristoffer Derwinger, MD PhD
Organizational Affiliation
Sahlgrenska University Hospital, Sweden
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sahlgrenska University Hospital
City
Gothenburg
ZIP/Postal Code
461 85
Country
Sweden
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
PK/PD Investigation of Modufolin (Arfolitixorin) in Plasma, Tumor and Adjacent Mucosa Adjacent Mucosa in Patients With Colon Cancer
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