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

Sponsor

Adherex Technologies, Inc. (Industry)

Overall Status

Unknown status

CT.gov ID

NCT01231802

Collaborator

(none)

140

Enrollment

Locations

Arms

21.1

Duration (Months)

8.8

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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 Design

Study Type:

Interventional

Anticipated 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 :

Apr 1, 2011

Anticipated Primary Completion Date :

Aug 1, 2012

Anticipated Study Completion Date :

Jan 1, 2013

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Progression-free survival [7.5 months]

Secondary Outcome Measures

To compare the tolerability and toxicity of orally administered eniluracil/5 FU/leucovorin regimen vs. capecitabine monotherapy [7.5 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banner MD Anderson Cancer Center	Gilbert	Arizona	United States	85234
2	The Methodist Hospital Cancer Center	Houston	Texas	United States	77030
3	Arkhangelsk Regional Clinical Oncology Center	Arkhangelsk		Russian Federation	163045
4	Chelyabinsk Regional Clinical Oncology	Chelyabinsk		Russian Federation	454087
5	Clinical Oncology Center #1	Krasnodar		Russian Federation
6	Leningrad Regional Oncology Center	Leningrad		Russian Federation
7	Moscow Hertzen Oncology Research Institute	Moscow		Russian Federation
8	Russian Oncological Research Center n.s. Blokhin	Moscow		Russian Federation
9	Orenburg Regional Clinical Oncology Center	Orenburg		Russian Federation
10	Pyatigorsk Oncology Center	Pyatigorsk		Russian Federation
11	Republic Oncology Center	Republic of Karelia		Russian Federation
12	Oncology Center No. 2 Krasnodar Regional Healthcare Dept	Sochi		Russian Federation	354057
13	City Clinical Oncology Center	St. Petersburg		Russian Federation
14	Laboratory of Thoracic Oncology of Research Institute of Pulmonary at St. Petersburg State Medical University n.a. I.P. Pavlov	St. Petersburg		Russian Federation
15	Road Clinical Hospital of the Russian Railways	St. Petersburg		Russian Federation
16	Stavropol Regional Clinical Oncology Center	Stavropol		Russian Federation