Study of Eniluracil + 5-Fluorouracil (5-FU) + Leucovorin Versus Capecitabine in Metastatic Breast Cancer
Metastatic Breast Cancer
About this trial
This is an interventional treatment trial for Metastatic Breast Cancer
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
Sites / Locations
- Banner MD Anderson Cancer CenterRecruiting
- The Methodist Hospital Cancer CenterRecruiting
- Arkhangelsk Regional Clinical Oncology CenterRecruiting
- Chelyabinsk Regional Clinical OncologyRecruiting
- Clinical Oncology Center #1Recruiting
- Leningrad Regional Oncology CenterRecruiting
- Moscow Hertzen Oncology Research InstituteRecruiting
- Russian Oncological Research Center n.s. BlokhinRecruiting
- Orenburg Regional Clinical Oncology CenterRecruiting
- Pyatigorsk Oncology CenterRecruiting
- Republic Oncology CenterRecruiting
- Oncology Center No. 2 Krasnodar Regional Healthcare DeptRecruiting
- City Clinical Oncology CenterRecruiting
- Laboratory of Thoracic Oncology of Research Institute of Pulmonary at St. Petersburg State Medical University n.a. I.P. PavlovRecruiting
- Road Clinical Hospital of the Russian RailwaysRecruiting
- Stavropol Regional Clinical Oncology CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Arm 1: Eniluracil/5-FU/Leucovorin
Arm 2: Capecitabine
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.
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