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

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.


Eligibility Criteria:
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