Study of Breast Cancer Prevention by Letrozole in High Risk Women - Full Text View

Purpose

This is a multi-institution double-blind placebo-controlled trial whose main objective is to determine if 6 months of letrozole (2.5 mg daily) can reduce proliferation as assessed by Ki-67 in high risk postmenopausal women on systemic hormone replacement therapy who have random periareolar fine needle aspiration (RPFNA) evidence of hyperplasia with atypia or borderline atypia, and a minimum Ki-67 of >1.5%.

The primary hypothesis is that proliferation and expression of other estrogen response genes will be favorably modulated by six months of letrozole relative to placebo without substantially increasing hot flashes or worsening overall quality of life.

Condition	Intervention	Phase
Breast Cancer	Drug: Letrozole Drug: Placebo	Phase II

Genetics Home Reference related topics:

breast cancer

MedlinePlus related topics:

Breast Cancer Cancer

ChemIDplus related topics:

Letrozole

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Official Title:	Study of Breast Cancer Prevention by Letrozole in High Risk Women

Further study details as provided by University of Kansas:

Primary Outcome Measures:

Assessment of proliferation rate (Ki-67 by immunocytochemistry) in benign breast epithelial cells acquired by random periareolar fine needle aspiration from women at high risk for the development of breast cancer. [ Time Frame: 6 Month ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Assessment of change in morphology by nuclear morphometry and the semi-quantitative Masood score index and change in qRT-PCR assessed estrogen response genes. [ Time Frame: 6 Months, 12 Months ] [ Designated as safety issue: No ]
Mammographic density and bioavialable estradiol and testosterone will be assessed as well. [ Time Frame: 6 Months, 12 Months ] [ Designated as safety issue: No ]
Change in biomarkers associated with bone and cardiovascular health, adverse events, BCPT Symptom Check List, hot flash score, general fatigue inventory, the Fibromyalgia Impact Questionnaire. [ Time Frame: 6 Months, 12 Months ] [ Designated as safety issue: No ]
25-OH vitamin D levels will be assessed. [ Time Frame: Baseline and 6 month 2 ] [ Designated as safety issue: No ]

Estimated Enrollment:	108
Study Start Date:	October 2006
Estimated Study Completion Date:	July 2011
Estimated Primary Completion Date:	July 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	Drug: Letrozole Letrozole 2.5 mg tablet daily. Then optional open label letrozole for another 6 months.
2: Placebo Comparator	Drug: Placebo Placebo tablet daily for 6 months then optional open label letrozole for 6 months.

Detailed Description:

Subsequent to the 6 month RPFNA for assessment of biomarkers, toxicity and quality of life assessments, all women may receive optional open-label letrozole for an additional 6 months, followed by a third RPFNA and biomarker

Eligibility

Ages Eligible for Study:	30 Years to 69 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Post-menopausal women at high risk for development of breast cancer
On a stable dose of hormone replacement therapy
have cytomophologic evidence of hyperplasia +/- atypia and Ki-67 expression >1.5% in benign breast epithelial cells acquired by RPFNA
Serum level of 25-OH vitamin D of at least 30 ng/ml prior to study entry
Willing to have a repeat RPFNA and mammogram at 6 months and 12 months (if participating in the open label portion of the study) following initiation of study drug

Exclusion Criteria:

Prior history of osteoporosis or osteoporotic fracture.
Prior history of invasive breast cancer or other invasive cancer within five years from date of study entry.
Current and chronic use of COX-2 specific inhibitors or NSAIDs
Receiving treatment for rheumatoid arthritis or fibromyalgia
Current history of poorly controlled migraines or perimenopausal symptoms
Currently receiving other investigational agents.
Receipt of more than 6 months of an aromatase inhibitor (anastrozole, exemestane, letrozole, etc.) at any time in the past.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00579826

Locations


United States, Kansas
	University of Kansas Medical Center	Recruiting
	Kansas City, Kansas, United States, 66160
	Contact: Bruce F Kimler, PhD 913-588-3660 bkimler@kumc.edu
	Principal Investigator: Carol J Fabian, MD

Sponsors and Collaborators

University of Kansas

Novartis

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Carol J Fabian, MD	University of Kansas

More Information

Responsible Party:	University of Kansas Medical Center ( Carol Fabian, MD )
Study ID Numbers:	10587
First Received:	December 18, 2007
Last Updated:	September 15, 2008
ClinicalTrials.gov Identifier:	NCT00579826
Health Authority:	United States: Food and Drug Administration

Study placed in the following topic categories:

Skin Diseases

Breast Neoplasms

Letrozole

Breast Diseases

Additional relevant MeSH terms:

Neoplasms

Neoplasms by Site

Molecular Mechanisms of Pharmacological Action

Antineoplastic Agents

Therapeutic Uses

Enzyme Inhibitors

Aromatase Inhibitors

Pharmacologic Actions

ClinicalTrials.gov processed this record on October 10, 2008

Sponsors and Collaborators:	University of Kansas Novartis National Cancer Institute (NCI)
Information provided by:	University of Kansas
ClinicalTrials.gov Identifier:	NCT00579826