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

NCT01231802 | Unknown Phase 2

• 1 other identifier: AHX-03-202
• Study Type: interventional
• Target: 140
• Locations: 2 countries
• Sites: 16

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.

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  7.5 months

Secondary Outcomes (1)

• To compare the tolerability and toxicity of orally administered eniluracil/5 FU/leucovorin regimen vs. capecitabine monotherapy

  7.5 months

Study Arms (2)

Arm 1: Eniluracil/5-FU/Leucovorin

EXPERIMENTAL

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; Drug: 5-Fluorouracil; Drug: Leucovorin

Arm 2: Capecitabine

ACTIVE COMPARATOR

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

Interventions

Eniluracil DRUG

Eniluracil (40 mg) orally at 18:00 ± 1 hour (6:00 PM) on Days 1, 8, \& 15

Arm 1: Eniluracil/5-FU/Leucovorin

5-Fluorouracil DRUG

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

Arm 1: Eniluracil/5-FU/Leucovorin

Leucovorin DRUG

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

Arm 1: Eniluracil/5-FU/Leucovorin

Capecitabine DRUG

Capecitabine (1000 mg/m2) twice daily (12 hr apart) for 14 consecutive days followed by 7 days off-treatment

Arm 2: Capecitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Adherex Technologies, Inc.: lead

Study Sites (16)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

RECRUITING

The Methodist Hospital Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Arkhangelsk Regional Clinical Oncology Center

Arkhangelsk, 163045, Russia

RECRUITING

Chelyabinsk Regional Clinical Oncology

Chelyabinsk, 454087, Russia

RECRUITING

Clinical Oncology Center #1

Krasnodar, Russia

RECRUITING

Moscow Hertzen Oncology Research Institute

Moscow, Russia

RECRUITING

Russian Oncological Research Center n.s. Blokhin

Moscow, Russia

RECRUITING

Orenburg Regional Clinical Oncology Center

Orenburg, Russia

RECRUITING

Pyatigorsk Oncology Center

Pyatigorsk, Russia

RECRUITING

Republic Oncology Center

Republic of Karelia, Russia

RECRUITING

City Clinical Oncology Center

Saint Petersburg, Russia

RECRUITING

Laboratory of Thoracic Oncology of Research Institute of Pulmonary at St. Petersburg State Medical University n.a. I.P. Pavlov

Saint Petersburg, Russia

RECRUITING

Leningrad Regional Oncology Center

Saint Petersburg, Russia

RECRUITING

Road Clinical Hospital of the Russian Railways

Saint Petersburg, Russia

RECRUITING

Oncology Center No. 2 Krasnodar Regional Healthcare Dept

Sochi, 354057, Russia

RECRUITING

Stavropol Regional Clinical Oncology Center

Stavropol, Russia

RECRUITING

Related Publications (1)

• Hoon SN, Lau PK, White AM, Bulsara MK, Banks PD, Redfern AD. Capecitabine for hormone receptor-positive versus hormone receptor-negative breast cancer. Cochrane Database Syst Rev. 2021 May 26;5(5):CD011220. doi: 10.1002/14651858.CD011220.pub2.

  PMID: 34037241 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

eniluracil; Fluorouracil; Leucovorin; Capecitabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

Gray Kirby, PharmD

CONTACT

919-614-3839; kirbyg@adherex.com

Anne McKay

CONTACT

919-949-2987; mckaya@adherex.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: October 27, 2010
• First Posted: November 1, 2010
• Study Start: April 1, 2011
• Primary Completion: August 1, 2012
• Study Completion: January 1, 2013
• Last Updated: July 17, 2012

Record last verified: 2012-07

Locations

US (2); RU (14)