Evaluation of Response to Two Schedules of Capecitabine in Patients With Metastatic Breast Cancer
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 350
- 试验地点
- 1
- 主要终点
- Progress Free Survival (PFS)
研究概览
简要总结
The purpose of this study is to compare the efficacy of a novel schedule of an oral anticancer drug, capecitabine, in patients with metastatic breast cancer.
Mathematical models have predicted that 7 days of capecitabine followed by 7 days of rest is an optimal dosing schedule for this drug and previous studies done al Memorial Sloan Kettering Cancer Center support the tolerability of this scheme.
This definitive, randomized trial comparing the efficacy of the new dosage with the conventional dosing schedule in patients with metastatic breast cancer is necessary and we hypothesize it will be superior in terms of efficacy.
Dosing schedules based on mathematical predictions for optimal drug delivery based on efficacy rather than toxicity could facilitate more rapid and economical drug development. This trial is a proof of principle trial of the highest priority.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •1 Subject Inclusion Criteria
- •Informed consent has been obtained.
- •Metastatic breast cancer.
- •Measurable or non-measurable disease per RECIST criteria.
- •Pathologic confirmation of breast cancer.
- •No limit to the number of prior chemotherapy regimens permitted for metastatic disease.
- •At least 3 weeks since prior chemotherapy. Patients should have recovered from all acute toxicity from such therapy (excluding alopecia).
- •Absolute Neutrophil Count (ANC )≥1.0; hemoglobin ≥9, platelets
- •AST, ALT and Alkaline phosphatase <2.5x upper limit of normal (or <5x upper limit of normal in the case of liver metastases). Total bilirubin <1.5x upper limit of normal.
- •Estimated creatinine clearance >50ml/min.
- •If female of childbearing potential, pregnancy test is negative and the patient agrees to use an effective method to avoid pregnancy during the study.
排除标准
- •HER2 over-expression and/or amplification as determined by immunohistochemistry (3+) or FISH (>2.0).
- •No prior fluoropyrimidine in the metastatic setting. Adjuvant fluoropyrimidine is permitted if >12 months have elapsed since treatment.
- •No restriction for prior hormonal therapy.
- •GI malabsorption syndrome which could impair oral drug absorption.
- •Concurrent use of warfarin is discouraged as drug interactions may make management of INR more difficult.
- •Central nervous system metastases are permitted if previously treated or clinically stable for at least 3 months.
- •Pregnant or nursing patients.
- •Life expectancy <3 months.
研究组 & 干预措施
Arm A: Capecitabine 2,000 mg (flat dose)
Arm A: Capecitabine 2,000 mg (flat dose), orally, twice daily for 7 days followed by a 7 day rest (7-7) (4-week cycle length ).
干预措施: Capecitabine (Drug)
Arm B: Capecitabine 1,000 mg/m2 twice daily for 14 day
Arm B: Capecitabine 1,000 mg/m2, orally, twice daily for 14 days followed by a 7 day rest (14-7) (3-week cycle length ). The control arm dose of capecitabine has been reduced from the US Food and Drug Administration approved dose of 1,250 mg/m2, orally, twice daily due to common clinical practice.
干预措施: Capecitabine (Drug)
结局指标
主要结局
Progress Free Survival (PFS)
时间窗: 24 month
The primary endpoint of this study is PFS, defined as the time from treatment start to progression or last date of follow-up. PFS will be estimated using Kaplan-Meier methods. This will be an intention to treat analysis. The Log-rank test will be used to test whether PFS is different for the two capecitabine schedules. It is hypothesized that the 7-7 schedule of capecitabine will have superior efficacy.
次要结局
- Number of patients with study withdrawal.(24 month)
- Number of participants with toxicity.(24 month)
- Number of patients with treatment delays.(24 month)
- Number of patients with dose reduction.(24 month)