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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Concentration of [6R]-5,10-methylene-THF in Tumor Tissue
研究概览
简要总结
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).
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •Any concurrent other anti-tumor therapy
- •Any prohibited concomitant medication within 30 days of surgery
- •Pregnancy or breast-feeding.
- •Second primary malignancy
研究组 & 干预措施
Levoleucovorin 200 mg/m2
One i.v. bolus injection of study drug after the patient has been anaesthetized.
干预措施: Levoleucovorin 200 mg/m2 (Drug)
Levoleucovorin 60 mg/m2
One i.v. bolus injection of study drug after the patient has been anaesthetized.
干预措施: Levoleucovorin 60 mg/m2 (Drug)
6R-MTHF 200 mg/m2
One i.v. bolus injection of study drug after the patient has been anaesthetized.
干预措施: 6R-MTHF (arfolitixorin) 200 mg/m2 (Drug)
6R-MTHF 60 mg/m2
One i.v. bolus injection of study drug after the patient has been anaesthetized.
干预措施: 6R-MTHF (arfolitixorin) 60 mg/m2 (Drug)
结局指标
主要结局
Concentration of [6R]-5,10-methylene-THF in Tumor Tissue
时间窗: 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.
Concentration of [6S]-5-THF in Adjacent Mucosa Tissue
时间窗: 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.
Concentration of [6S]-5-formyl-THF in Adjacent Mucosa Tissue
时间窗: 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.
Concentration of [6R]-5,10-methylene-THF in Adjacent Mucosa Tissue
时间窗: 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.
Concentration of [6S]-5-methyl-THF in Tumor Tissue
时间窗: 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.
Concentration of [6S]-5-formyl-THF in Tumor Tissue
时间窗: 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.
Concentration of [6S]-5-THF in Tumor Tissue
时间窗: 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.
Concentration of [6S]-5-methyl-THF in Adjacent Mucosa Tissue
时间窗: 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.
次要结局
- Cmax of [6S]-5-THF in Plasma(Samples taken Day 1 (Day of surgery) and Day 2)
- AUC(Last) of [6S]-5-methyl-THF(Samples taken Day 1 (Day of surgery) and Day 2)
- Cmax of [6R]-5,10-methylene-THF(Samples taken Day 1 (Day of surgery) and Day 2)
- Cmax of [6S]-5-methyl-THF in Plasma(Samples taken Day 1 (Day of surgery) and Day 2)
- Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6S]-5-methyl-THF(Samples taken Day 1 (Day of surgery))
- AUC(Last) of [6R]-5,10-methylene-THF(Samples taken Day 1 (Day of surgery) and Day 2)
- Tmax of [6R]-5,10-methylene-THF(Samples taken Day 1 (Day of surgery) and Day 2)
- Tmax of [6S]-5-formyl-THF(Samples taken Day 1 (Day of surgery) and Day 2)
- T(1/2) of [6S]-5-THF(Samples taken Day 1 (Day of surgery) and Day 2)
- Cmax of [6S]-5-formyl-THF in Plasma(Samples taken Day 1 (Day of surgery) and Day 2)
- AUC(0-2h) of [6R]-5,10-methylene-THF(Samples taken Day 1 (Day of surgery))
- AUC(0-2h) of [6S]-5-THF(Samples taken Day 1 (Day of surgery))
- AUC(0-2h) of [6S]-5-methyl-THF(Samples taken Day 1 (Day of surgery))
- AUC(0-2h) of [6SR]-5-formyl-THF(Samples taken Day 1 (Day of surgery))
- AUC(Last) of [6S]-5-THF(Samples taken Day 1 (Day of surgery) and Day 2)
- AUC(Last) of [6S]-5-formyl-THF(Samples taken Day 1 (Day of surgery) and Day 2)
- Tmax of [6S]-5-THF(Samples taken Day 1 (Day of surgery) and Day 2)
- T(1/2) of [6S]-5-methyl-THF(Samples taken Day 1 (Day of surgery) and Day 2)
- T(Last) of [6S]-5-methyl-THF(Samples taken Day 1 (Day of surgery) and Day 2)
- Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6S]-5-THF(Samples taken Day 1 (Day of surgery))
- Correlation of Gene Expression in Tumor and Adjacent Mucosa(Sample taken Day 1 (Day of Surgery))
- Change in Homocystein Concentration From Screening(Samples taken at Screening visit, Day 2 and End of Study (Day 5))
- Number of AEs Per Severity(Screening visit until end of study, Day 5)
- Tmax of [6S]-5-methyl-THF(Samples taken Day 1 (Day of surgery) and Day 2)
- T(1/2) of [6R]-5,10-methylene-THF(Samples taken Day 1 (Day of surgery) and Day 2)
- T(1/2) of [6S]-5-formyl-THF(Samples taken Day 1 (Day of surgery) and Day 2)
- Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6R]-5,10-methylene-THF(Samples taken Day 1 (Day of surgery))
- Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6S]-5-formyl-THF(Samples taken Day 1 (Day of surgery))
- Gene Expression Ratios (Mucosa:Tumor)(Sample taken Day 1 (Day of Surgery))
- T(Last) of [6R]-5,10-methylene-THF(Samples taken Day 1 (Day of surgery) and Day 2)
- T(Last) of [6S]-5-THF(Samples taken Day 1 (Day of surgery) and Day 2)
- T(Last) of [6S]-5-formyl-THF(Samples taken Day 1 (Day of surgery) and Day 2)
- Homocystein Concentration(Samples taken at Screening visit, Day 2, and End of Study (Day 5))
- Change in S-Folate Concentration From Screening(Samples taken at Screening visit, Day 2 and End of Study (Day 5))
- S-Folate Concentration(Samples taken at Screening visit, Day 2 and End of Study (Day 5))