study of eniluracil + 5-fluorouracil (5-fu) + leucovorin versus capecitabine in metastatic breast cancer

Conditions: Metastatic Breast Cancer

Summary: 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