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

Phase 2

• Conditions: Metastatic Breast Cancer
• Interventions: Drug: Capecitabine; Drug: Eniluracil; Drug: 5-Fluorouracil; Drug: Leucovorin

• 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

Study Timeline

• Study First Submitted: 2010-10-27
• Study First Submitted QC: 2010-10-29
• Study First Posted: 2010-11-01
• Study Start: 2011-04
• Status Verified: 2012-07
• Last Update Submitted: 2012-07-16
• Last Update Posted: 2012-07-17
• Primary Completion: 2012-08
• Study Completion: 2013-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 140

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

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)

Banner MD Anderson Cancer Center; 🇺🇸 Gilbert, Arizona, United States

The Methodist Hospital Cancer Center; 🇺🇸 Houston, Texas, United States

Arkhangelsk Regional Clinical Oncology Center; 🇷🇺 Arkhangelsk, Russian Federation

Chelyabinsk Regional Clinical Oncology; 🇷🇺 Chelyabinsk, Russian Federation

Clinical Oncology Center #1; 🇷🇺 Krasnodar, Russian Federation

Leningrad Regional Oncology Center; 🇷🇺 Leningrad, Russian Federation

Moscow Hertzen Oncology Research Institute; 🇷🇺 Moscow, Russian Federation

Russian Oncological Research Center n.s. Blokhin; 🇷🇺 Moscow, Russian Federation

Orenburg Regional Clinical Oncology Center; 🇷🇺 Orenburg, Russian Federation

Pyatigorsk Oncology Center; 🇷🇺 Pyatigorsk, Russian Federation

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