A Comparative, Multicenter, Open-Label, Randomized, Phase 2 Study of the Safety and Antitumor Activity of Oral Eniluracil + 5 Fluorouracil + Leucovorin Versus Capecitabine Monotherapy in Subjects With Metastatic Breast Cancer
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 140
- 试验地点
- 16
- 主要终点
- Progression-free survival
研究概览
简要总结
The purpose of the study is to determine if eniluracil/5-FU/leucovorin in metastatic breast cancer (MBC) may have efficacy and tolerability advantages over capecitabine monotherapy.
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
- None
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
- •Histologically or cytologically confirmed metastatic (Stage IV) adenocarcinoma of the breast
- •Prior exposure to anthracyclines either in the neoadjuvant/adjuvant setting, or as treatment for metastatic disease
- •Either evidence of a recurrence or development of metastatic disease at least 12 months after the last dose of a taxane as neoadjuvant/adjuvant therapy, or evidence of disease progression while receiving a taxane for metastatic disease
- •ECOG Performance Status of 0 or 1
- •Measurable disease according to RECIST 1.1 Criteria
- •Adequate renal, hematologic, and hepatic function
- •Negative pregnancy test and willing to use effective contraception
- •Willing to avoid any other dose or form (iv, oral, or topical) of 5 FU or related derivatives for 8 weeks following the last dose of eniluracil
- •Willing to be closely monitored for changes in coagulation parameters (prothrombin time and/or international normalized ratio [INR] values) if receiving concomitant warfarin
排除标准
- •Pregnant or lactating females
- •Prior treatment with capecitabine
- •More than one prior chemotherapy regimen for metastatic disease
- •Prior radiation must not have included ≥ 30% of major bone marrow-containing areas (pelvis, lumbar spine). If prior radiation was < 30%, then a minimum interval of 6 weeks must be allowed between the last radiation treatment and administration of either study arm.
- •Currently receiving anti-cancer therapy
- •Residual ≥ Grade 2 clinically significant side effects (excluding alopecia) associated with prior radiotherapy, chemotherapy, and investigational treatments
- •Unstable CNS metastases. However, subjects that are asymptomatic and off systemic steroids and anticonvulsants for at least 3 months are not excluded.
- •Malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach or small bowel, ulcerative colitis, recent history of GI bleeding or perforation
- •History of other malignancy, except subjects who have been disease-free for 5 years or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma
- •Concurrent disease or condition that would make the subject inappropriate for study participation, or any serious medical disorder that would interfere with the subject's safety
- •Known history or clinical evidence of leptomeningeal carcinomatosis
- •Active or uncontrolled infection
- •Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent
- •Known history of uncontrolled or symptomatic angina, arrhythmia or congestive heart failure
- •Concurrent treatment with an investigational agent
- •Use of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study medication
- •Taking phenytoin
- •Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to capecitabine, fluorouracil, leucovorin, or any excipients
- •Known dihydropyrimidine dehydrogenase (DPD) deficiency
研究组 & 干预措施
Arm 1: Eniluracil/5-FU/Leucovorin
Arm 1: (weekly, 28-day cycle): Approximately eighty subjects will orally self-administer eniluracil approximately 13 hr (range of 11-16 hr) before receiving 5 FU and leucovorin. The next day they will orally self-administer 5-FU and leucovorin. On the third day, they will orally self-administer leucovorin. The regimen is taken once per week for three consecutive weeks followed by one-week off-treatment.
干预措施: Eniluracil (Drug)
Arm 1: Eniluracil/5-FU/Leucovorin
Arm 1: (weekly, 28-day cycle): Approximately eighty subjects will orally self-administer eniluracil approximately 13 hr (range of 11-16 hr) before receiving 5 FU and leucovorin. The next day they will orally self-administer 5-FU and leucovorin. On the third day, they will orally self-administer leucovorin. The regimen is taken once per week for three consecutive weeks followed by one-week off-treatment.
干预措施: 5-Fluorouracil (Drug)
Arm 1: Eniluracil/5-FU/Leucovorin
Arm 1: (weekly, 28-day cycle): Approximately eighty subjects will orally self-administer eniluracil approximately 13 hr (range of 11-16 hr) before receiving 5 FU and leucovorin. The next day they will orally self-administer 5-FU and leucovorin. On the third day, they will orally self-administer leucovorin. The regimen is taken once per week for three consecutive weeks followed by one-week off-treatment.
干预措施: Leucovorin (Drug)
Arm 2: Capecitabine
Arm 2: (bid daily, 21-day cycle): Approximately sixty subjects will self-administer oral capecitabine (1000 mg/m2) twice daily (12 hr apart) for 14 consecutive days followed by 7 days off-treatment
干预措施: Capecitabine (Drug)
结局指标
主要结局
Progression-free survival
时间窗: 7.5 months
次要结局
- To compare the tolerability and toxicity of orally administered eniluracil/5 FU/leucovorin regimen vs. capecitabine monotherapy(7.5 months)