Study of Eniluracil + 5-Fluorouracil (5-FU) + Leucovorin Versus Capecitabine in Metastatic Breast Cancer
- Conditions
- Metastatic Breast Cancer
- Interventions
- Registration Number
- NCT01231802
- Lead Sponsor
- Adherex Technologies, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- Female
- Target Recruitment
- 140
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1: Eniluracil/5-FU/Leucovorin 5-Fluorouracil 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: Capecitabine Capecitabine 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 Arm 1: Eniluracil/5-FU/Leucovorin Leucovorin 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 1: Eniluracil/5-FU/Leucovorin Eniluracil 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.
- Primary Outcome Measures
Name Time Method Progression-free survival 7.5 months
- Secondary Outcome Measures
Name Time Method To compare the tolerability and toxicity of orally administered eniluracil/5 FU/leucovorin regimen vs. capecitabine monotherapy 7.5 months
Trial Locations
- Locations (16)
Chelyabinsk Regional Clinical Oncology
🇷🇺Chelyabinsk, Russian Federation
Republic Oncology Center
🇷🇺Republic of Karelia, Russian Federation
Stavropol Regional Clinical Oncology Center
🇷🇺Stavropol, Russian Federation
Leningrad Regional Oncology Center
🇷🇺Leningrad, Russian Federation
Russian Oncological Research Center n.s. Blokhin
🇷🇺Moscow, Russian Federation
The Methodist Hospital Cancer Center
🇺🇸Houston, Texas, United States
Moscow Hertzen Oncology Research Institute
🇷🇺Moscow, Russian Federation
City Clinical Oncology Center
🇷🇺St. Petersburg, Russian Federation
Laboratory of Thoracic Oncology of Research Institute of Pulmonary at St. Petersburg State Medical University n.a. I.P. Pavlov
🇷🇺St. Petersburg, Russian Federation
Clinical Oncology Center #1
🇷🇺Krasnodar, Russian Federation
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
Arkhangelsk Regional Clinical Oncology Center
🇷🇺Arkhangelsk, Russian Federation
Orenburg Regional Clinical Oncology Center
🇷🇺Orenburg, Russian Federation
Road Clinical Hospital of the Russian Railways
🇷🇺St. Petersburg, Russian Federation
Pyatigorsk Oncology Center
🇷🇺Pyatigorsk, Russian Federation
Oncology Center No. 2 Krasnodar Regional Healthcare Dept
🇷🇺Sochi, Russian Federation