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