Study of Eniluracil + 5-Fluorouracil (5-FU) + Leucovorin Versus Capecitabine in Metastatic Breast Cancer

Inclusion Criteria:

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

Exclusion Criteria:

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