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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01231802
Recruitment Status : Unknown
Verified July 2012 by Adherex Technologies, Inc..
Recruitment status was:  Recruiting
First Posted : November 1, 2010
Last Update Posted : July 17, 2012
Information provided by:
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.

Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Drug: Eniluracil Drug: 5-Fluorouracil Drug: Leucovorin Drug: Capecitabine Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Comparative, Multicenter, Open-Label, Randomized, Phase 2 Study of the Safety and Antitumor Activity of Oral Eniluracil + 5 Fluorouracil + Leucovorin Versus Capecitabine Monotherapy in Subjects With Metastatic Breast Cancer
Study Start Date : April 2011
Estimated Primary Completion Date : August 2012
Estimated Study Completion Date : January 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Arm 1: Eniluracil/5-FU/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.
Drug: Eniluracil
Eniluracil (40 mg) orally at 18:00 ± 1 hour (6:00 PM) on Days 1, 8, & 15

Drug: 5-Fluorouracil
5-FU (30 mg/m2) orally at 7:00 AM ± 1 hour on Days 2, 9, & 16

Drug: Leucovorin
Leucovorin (30 mg) orally at 7:00 AM ± 2 hours on Days 2, 3, 9, 10, 16, & 17

Active Comparator: Arm 2: 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
Drug: Capecitabine
Capecitabine (1000 mg/m2) twice daily (12 hr apart) for 14 consecutive days followed by 7 days off-treatment

Primary Outcome Measures :
  1. Progression-free survival [ Time Frame: 7.5 months ]

Secondary Outcome Measures :
  1. To compare the tolerability and toxicity of orally administered eniluracil/5 FU/leucovorin regimen vs. capecitabine monotherapy [ Time Frame: 7.5 months ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01231802

Contact: Gray Kirby, PharmD 919-614-3839
Contact: Anne McKay 919-949-2987

United States, Arizona
Banner MD Anderson Cancer Center Recruiting
Gilbert, Arizona, United States, 85234
United States, Texas
The Methodist Hospital Cancer Center Recruiting
Houston, Texas, United States, 77030
Russian Federation
Arkhangelsk Regional Clinical Oncology Center Recruiting
Arkhangelsk, Russian Federation, 163045
Chelyabinsk Regional Clinical Oncology Recruiting
Chelyabinsk, Russian Federation, 454087
Clinical Oncology Center #1 Recruiting
Krasnodar, Russian Federation
Leningrad Regional Oncology Center Recruiting
Leningrad, Russian Federation
Moscow Hertzen Oncology Research Institute Recruiting
Moscow, Russian Federation
Russian Oncological Research Center n.s. Blokhin Recruiting
Moscow, Russian Federation
Orenburg Regional Clinical Oncology Center Recruiting
Orenburg, Russian Federation
Pyatigorsk Oncology Center Recruiting
Pyatigorsk, Russian Federation
Republic Oncology Center Recruiting
Republic of Karelia, Russian Federation
Oncology Center No. 2 Krasnodar Regional Healthcare Dept Recruiting
Sochi, Russian Federation, 354057
City Clinical Oncology Center Recruiting
St. Petersburg, Russian Federation
Laboratory of Thoracic Oncology of Research Institute of Pulmonary at St. Petersburg State Medical University n.a. I.P. Pavlov Recruiting
St. Petersburg, Russian Federation
Road Clinical Hospital of the Russian Railways Recruiting
St. Petersburg, Russian Federation
Stavropol Regional Clinical Oncology Center Recruiting
Stavropol, Russian Federation
Sponsors and Collaborators
Adherex Technologies, Inc.

Responsible Party: Gray Kirby/Clinical Project Manager, Adherex Technologies, Inc. Identifier: NCT01231802     History of Changes
Other Study ID Numbers: AHX-03-202
First Posted: November 1, 2010    Key Record Dates
Last Update Posted: July 17, 2012
Last Verified: July 2012

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Enzyme Inhibitors