Clinical trial NCT01681472: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: 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
Lead sponsor: Isofol Medical AB
Sponsor class: INDUSTRY
First posted: 2012-09-10
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Concentration of [6R]-5,10-methylene-THF in Tumor Tissue
timeFrame: 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
measure: Concentration of [6R]-5,10-methylene-THF in Adjacent Mucosa Tissue
timeFrame: 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
measure: Concentration of [6S]-5-THF in Tumor Tissue
timeFrame: 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
measure: Concentration of [6S]-5-THF in Adjacent Mucosa Tissue
timeFrame: 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
measure: Concentration of [6S]-5-methyl-THF in Tumor Tissue
timeFrame: 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
measure: Concentration of [6S]-5-methyl-THF in Adjacent Mucosa Tissue
timeFrame: 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
measure: Concentration of [6S]-5-formyl-THF in Tumor Tissue
timeFrame: 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
measure: Concentration of [6S]-5-formyl-THF in Adjacent Mucosa Tissue
timeFrame: 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 outcomes:
measure: AUC(0-2h) of [6R]-5,10-methylene-THF
timeFrame: Samples taken Day 1 (Day of surgery)
measure: AUC(0-2h) of [6S]-5-THF
timeFrame: Samples taken Day 1 (Day of surgery)
measure: AUC(0-2h) of [6S]-5-methyl-THF
timeFrame: Samples taken Day 1 (Day of surgery)
measure: AUC(0-2h) of [6SR]-5-formyl-THF
timeFrame: Samples taken Day 1 (Day of surgery)
measure: AUC(Last) of [6R]-5,10-methylene-THF
timeFrame: Samples taken Day 1 (Day of surgery) and Day 2
measure: AUC(Last) of [6S]-5-THF
timeFrame: Samples taken Day 1 (Day of surgery) and Day 2
measure: AUC(Last) of [6S]-5-methyl-THF
timeFrame: Samples taken Day 1 (Day of surgery) and Day 2
measure: AUC(Last) of [6S]-5-formyl-THF
timeFrame: Samples taken Day 1 (Day of surgery) and Day 2
measure: Cmax of [6R]-5,10-methylene-THF
timeFrame: Samples taken Day 1 (Day of surgery) and Day 2
measure: Cmax of [6S]-5-THF in Plasma
timeFrame: Samples taken Day 1 (Day of surgery) and Day 2
measure: Cmax of [6S]-5-methyl-THF in Plasma
timeFrame: Samples taken Day 1 (Day of surgery) and Day 2
measure: Cmax of [6S]-5-formyl-THF in Plasma
timeFrame: Samples taken Day 1 (Day of surgery) and Day 2
measure: Tmax of [6R]-5,10-methylene-THF
timeFrame: Samples taken Day 1 (Day of surgery) and Day 2
measure: Tmax of [6S]-5-THF
timeFrame: Samples taken Day 1 (Day of surgery) and Day 2
measure: Tmax of [6S]-5-methyl-THF
timeFrame: Samples taken Day 1 (Day of surgery) and Day 2
measure: Tmax of [6S]-5-formyl-THF
timeFrame: Samples taken Day 1 (Day of surgery) and Day 2
measure: T(1/2) of [6R]-5,10-methylene-THF
timeFrame: Samples taken Day 1 (Day of surgery) and Day 2
measure: T(1/2) of [6S]-5-THF
timeFrame: Samples taken Day 1 (Day of surgery) and Day 2
measure: T(1/2) of [6S]-5-methyl-THF
timeFrame: Samples taken Day 1 (Day of surgery) and Day 2
measure: T(1/2) of [6S]-5-formyl-THF
timeFrame: Samples taken Day 1 (Day of surgery) and Day 2
measure: T(Last) of [6R]-5,10-methylene-THF
timeFrame: Samples taken Day 1 (Day of surgery) and Day 2
measure: T(Last) of [6S]-5-THF
timeFrame: Samples taken Day 1 (Day of surgery) and Day 2
measure: T(Last) of [6S]-5-methyl-THF
timeFrame: Samples taken Day 1 (Day of surgery) and Day 2
measure: T(Last) of [6S]-5-formyl-THF
timeFrame: Samples taken Day 1 (Day of surgery) and Day 2
measure: Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6R]-5,10-methylene-THF
timeFrame: Samples taken Day 1 (Day of surgery)
measure: Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6S]-5-THF
timeFrame: Samples taken Day 1 (Day of surgery)
measure: Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6S]-5-methyl-THF
timeFrame: Samples taken Day 1 (Day of surgery)
measure: Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6S]-5-formyl-THF
timeFrame: Samples taken Day 1 (Day of surgery)
measure: Gene Expression Ratios (Mucosa:Tumor)
timeFrame: Sample taken Day 1 (Day of Surgery)
measure: Correlation of Gene Expression in Tumor and Adjacent Mucosa
timeFrame: Sample taken Day 1 (Day of Surgery)
measure: Homocystein Concentration
timeFrame: Samples taken at Screening visit, Day 2, and End of Study (Day 5)
measure: S-Folate Concentration
timeFrame: Samples taken at Screening visit, Day 2 and End of Study (Day 5)
measure: Change in Homocystein Concentration From Screening
timeFrame: Samples taken at Screening visit, Day 2 and End of Study (Day 5)
measure: Change in S-Folate Concentration From Screening
timeFrame: Samples taken at Screening visit, Day 2 and End of Study (Day 5)
measure: Number of AEs Per Severity
timeFrame: Screening visit until end of study, Day 5
Other outcomes:
Locations:
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital
Study officials:
affiliation: Sahlgrenska University Hospital
name: Kristoffer Derwinger, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: