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

Metastatic Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01231802
• Other study ID #: AHX-03-202
• Status: Recruiting
• Phase: Phase 2
• First received: October 27, 2010
• Last updated: July 16, 2012
• Start date: April 2011
• Est. completion date: January 2013

Study information

• Verified date: July 2012
• Source: Adherex Technologies, Inc.
• Contact: Gray Kirby, PharmD
• Phone: 919-614-3839
• Email: kirbyg[@]adherex.com
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationRussia: Ministry of Health of the Russian Federation
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: January 2013
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Eniluracil
Eniluracil (40 mg) orally at 18:00 ± 1 hour (6:00 PM) on Days 1, 8, & 15
• 5-Fluorouracil
5-FU (30 mg/m2) orally at 7:00 AM ± 1 hour on Days 2, 9, & 16
• Leucovorin
Leucovorin (30 mg) orally at 7:00 AM ± 2 hours on Days 2, 3, 9, 10, 16, & 17
• Capecitabine
Capecitabine (1000 mg/m2) twice daily (12 hr apart) for 14 consecutive days followed by 7 days off-treatment

Locations

Country	Name	City	State
Russian Federation	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	Republic Oncology Center	Republic of Karelia
Russian Federation	Oncology Center No. 2 Krasnodar Regional Healthcare Dept	Sochi
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	Road Clinical Hospital of the Russian Railways	St. Petersburg
Russian Federation	Stavropol Regional Clinical Oncology Center	Stavropol
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	The Methodist Hospital Cancer Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Adherex Technologies, Inc.

Countries where clinical trial is conducted

United States,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival		7.5 months	No
Secondary	To compare the tolerability and toxicity of orally administered eniluracil/5 FU/leucovorin regimen vs. capecitabine monotherapy		7.5 months	Yes