Clinical trial NCT01231802: Study of Eniluracil + 5-Fluorouracil (5-FU) + Leucovorin Versus Capecitabine in Metastatic Breast Cancer
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Metastatic Breast Cancer
Lead sponsor: Adherex Technologies, Inc.
Sponsor class: INDUSTRY
First posted: 2010-11-01
Enrollment: 140
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Progression-free survival
timeFrame: 7.5 months
Secondary outcomes:
measure: To compare the tolerability and toxicity of orally administered eniluracil/5 FU/leucovorin regimen vs. capecitabine monotherapy
timeFrame: 7.5 months
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Houston
country: United States
facility: The Methodist Hospital Cancer Center
state: Texas
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk Regional Clinical Oncology Center
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Regional Clinical Oncology
city: Krasnodar
country: Russian Federation
facility: Clinical Oncology Center #1
city: Leningrad
country: Russian Federation
facility: Leningrad Regional Oncology Center
city: Moscow
country: Russian Federation
facility: Moscow Hertzen Oncology Research Institute
city: Moscow
country: Russian Federation
facility: Russian Oncological Research Center n.s. Blokhin
city: Orenburg
country: Russian Federation
facility: Orenburg Regional Clinical Oncology Center
city: Pyatigorsk
country: Russian Federation
facility: Pyatigorsk Oncology Center
city: Republic of Karelia
country: Russian Federation
facility: Republic Oncology Center
city: Sochi
country: Russian Federation
facility: Oncology Center No. 2 Krasnodar Regional Healthcare Dept
city: St. Petersburg
country: Russian Federation
facility: City Clinical Oncology Center
city: St. Petersburg
country: Russian Federation
facility: Laboratory of Thoracic Oncology of Research Institute of Pulmonary at St. Petersburg State Medical University n.a. I.P. Pavlov
city: St. Petersburg
country: Russian Federation
facility: Road Clinical Hospital of the Russian Railways
city: Stavropol
country: Russian Federation
facility: Stavropol Regional Clinical Oncology Center
Study officials:
References:
citation: 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.