A Prospective Evaluation of Capecitabine and Metabolite Pharmacokinetics in Elderly Breast and Colorectal Cancer Patients and Their Association With Toxicity and Molecular Markers of Enzyme Activity and Aging
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 100
- 主要终点
- Area under the curve (AUC) of capecitabine and metabolites
研究概览
简要总结
This is a multi-centre prospective non-interventional study designed to evaluate the effects of patient age on the pharmacokinetics of capecitabine and its metabolites 5'DFCR, 5'DFUR, and 5-FU. In addition, the study will assess the correlation between the pharmacokinetic parameters calculated and cytidine deaminase, biomarkers of aging, clinical frailty, treatment outcome, and toxicity. To be enrolled, patients must have breast or colorectal cancer and be eligible to receive capecitabine monotherapy in accordance with its approved clinical usage in the UK. Treatment will be administered according to NICE guidelines as well as the clinical judgement of the prescribing physician. One hundred patients (50 breast cancer patients, 50 colorectal cancer patients) who are about to start treatment with capecitabine monotherapy will be recruited to the study and undergo study procedures within the first week of treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
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
- •Histologic or cytologic diagnosis of breast cancer or colorectal cancer. Patients should have disease that is suitable for capecitabine monotherapy as defined by the NICE Guidelines.
- •Patients must be within the first week of their first cycle of capecitabine treatment.
- •Estimated life expectancy of greater than 3 months. 4) Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or
- •Total serum bilirubin less than or equal to 25 micromol/L. 6) Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels less than 2.5 times the upper limit of the normal range.
- •Serum albumin level greater than 32 g/L. 8) Creatinine clearance greater than or equal to 30 mL/minute. 9) Blood haemoglobin level of greater than 9 g/dL, with transfusion allowed. 10) Absolute neutrophil count greater than 2.5 x 109/L. 11) Platelet count greater than 100 x 109/L. 12) 18 years of age or older. 13) Written informed consent.
排除标准
- •Pregnancy or breast feeding.
- •Known HIV, Hepatitis B, or Hepatitis C infection.
- •Known Gilbert syndrome.
- •Uncontrolled diabetes (HbA1c greater than 7.5%).
- •Any condition or disease that might affect oral absorption of medications, including:
- •Crohn's disease
- •Ulcerative colitis
- •Major gastric or small bowel resection
研究组 & 干预措施
Capecitabine
干预措施: Capecitabine (Drug)
结局指标
主要结局
Area under the curve (AUC) of capecitabine and metabolites
时间窗: 0 (pre-dose), 0.5, 1, 2, 4, and 6 hours post dose
Measurement of AUC of capecitabine and its metabolites 5'deoxy-5-fluorocytidine (5'DFCR), 5'deoxy-5-fluorouridine (5'DFUR), and 5-fluorouracil.
次要结局
- Grip strength measured in kg(During 6-hour pharmacokinetic study session)
- Progression free survival as measured by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1(From time of enrollment until first documented progression)
- Frailty as measured by the Edmonton Frail Scale(During 6-hour pharmacokinetic study session)
- Toxicities and grades as scaled by Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.03(Six months)
- Plasma cytidine deaminase activity (measured in units/mg protein by spectrophotometric assay)(0 hours post dose (pre-dose))
- Maximum plasma concentration (Cmax) of capecitabine and metabolites(0 (pre-dose), 0.5, 1, 2, 4, and 6 hours post dose)
- Response as measured by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1(From time of enrollment to first documented response)
- Nutritional status as measured by the Mini Nutritional Assessment questionnaire(During 6-hour pharmacokinetic study session)
- Quality of life as assessed by the European Organization for Research and Treatment of Cancer quality of life (EORTC-QLQ-C30 version 3) questionnaire(During 6-hour pharmacokinetic study session)
- Time of maximum plasma concentration (Tmax) of capecitabine and metabolites(0 (pre-dose), 0.5, 1, 2, 4, and 6 hours post dose)