Metastatic Breast Cancer
Conditions
Brief 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.
Interventions
DRUGEniluracil
Eniluracil (40 mg) orally at 18:00 ± 1 hour (6:00 PM) on Days 1, 8, & 15
DRUG5-Fluorouracil
5-FU (30 mg/m2) orally at 7:00 AM ± 1 hour on Days 2, 9, & 16
DRUGLeucovorin
Leucovorin (30 mg) orally at 7:00 AM ± 2 hours on Days 2, 3, 9, 10, 16, & 17
DRUGCapecitabine
Capecitabine (1000 mg/m2) twice daily (12 hr apart) for 14 consecutive days followed by 7 days off-treatment
Sponsors
Adherex Technologies, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free survival | 7.5 months |
Secondary
| Measure | Time frame |
|---|---|
| To compare the tolerability and toxicity of orally administered eniluracil/5 FU/leucovorin regimen vs. capecitabine monotherapy | 7.5 months |
Countries
Russia, United States
Contacts
Primary ContactGray Kirby, PharmD
Backup ContactAnne McKay
Outcome results
None listed