Letrozole in Preventing Breast Cancer in Healthy Postmenopausal Women at High Risk for Breast Cancer

NCT01077453 | Completed Phase 1

• 5 other identifiers: NCI-2013-0075709-0869-04UAZ08-12-02N01CN35158P30CA023074
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 3

Brief Summary

This randomized phase I trial studies the side effects and the best dose of letrozole in preventing breast cancer in healthy postmenopausal women at high risk for breast cancer. Chemoprevention is the use of drugs to keep breast cancer from forming or coming back. The use of letrozole may keep cancer from forming in healthy postmenopausal women at high risk for breast cancer.

Conditions

Healthy, no Evidence of Disease; Lobular Breast Carcinoma in Situ

Outcome Measures

Primary Outcomes (1)

• Percentage of serum estradiol suppression in postmenopausal women at high risk for breast cancer

  Three one-sided two-sample t-tests will be conducted on the ratios of the mean percentage of suppression simultaneously to test for non-inferiority. A multivariate t-distribution is used to derive the critical value and the power.

  Baseline to week 30

Secondary Outcomes (4)

• Change in serum estrone levels

  Baseline to week 30

• Change in serum testosterone levels

  Baseline to week 30

• Menopausal symptoms as assessed by quality of life measures, as assessed by Medical Outcomes Study 36-item Short Form Health Survey (SF-36) and Menopause Specific Quality of Life Questionnaire (MENQOL)

  Up to week 30

• Nuclear chromatin abnormality as assessed by karyometry

  Up to week 30

Other Outcomes (2)

• Prevalence of breast cancer stem cells by the proportion of aldehyde dehydrogenase positive cells, assessed by the Aldeflour assay

  Up to week 30

• Relative expression of stem cell markers to housekeeping genes, assessed by quantitative real time polymerase chain reaction

  Up to week 30

Study Arms (4)

Arm I (2.5 mg letrozole)

EXPERIMENTAL

Patients receive 2.5 mg of letrozole PO thrice weekly for 6 months.

Drug: letrozole; Other: quality-of-life assessment; Other: laboratory biomarker analysis

Arm II (1.0 mg letrozole)

EXPERIMENTAL

Patients receive 1.0 mg of letrozole PO thrice weekly for 6 months.

Drug: letrozole; Other: quality-of-life assessment; Other: laboratory biomarker analysis

Arm III (0.25 mg letrozole)

EXPERIMENTAL

Patients receive 0.25 mg of letrozole PO thrice weekly for 6 months.

Drug: letrozole; Other: quality-of-life assessment; Other: laboratory biomarker analysis

Arm IV (2.5 mg letrozole)

EXPERIMENTAL

Patients receive 2.5 mg of letrozole PO once daily for 6 months.

Drug: letrozole; Other: quality-of-life assessment; Other: laboratory biomarker analysis

Interventions

letrozole DRUG

Given orally

Also known as: CGS 20267, Femara, LTZ

Arm I (2.5 mg letrozole); Arm II (1.0 mg letrozole); Arm III (0.25 mg letrozole); Arm IV (2.5 mg letrozole)

quality-of-life assessment OTHER

Ancillary studies

Also known as: quality of life assessment

Arm I (2.5 mg letrozole); Arm II (1.0 mg letrozole); Arm III (0.25 mg letrozole); Arm IV (2.5 mg letrozole)

laboratory biomarker analysis OTHER

Correlative studies

Arm I (2.5 mg letrozole); Arm II (1.0 mg letrozole); Arm III (0.25 mg letrozole); Arm IV (2.5 mg letrozole)

Eligibility Criteria

• Age: 35 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy postmenopausal women at "high risk" for breast cancer will be eligible for the study; definition of menopause will be:
• Amenorrhea for at least 12 months, or
• History of hysterectomy and bilateral salpingo-oophorectomy, or
• At least 55 years of age with prior hysterectomy with or without oophorectomy, or
• Age 35 to 54 with a prior hysterectomy without oophorectomy OR with a status of ovaries unknown with documented follicle-stimulating hormone level demonstrating elevation in postmenopausal range
• "High risk" for breast cancer will be defined as:
• Prior histologically confirmed lobular carcinoma in situ (LCIS) treated by local excision only, or
• At least 1.66% probability of invasive breast cancer within 5 years using the Breast Cancer Risk Assessment Tool
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1; Karnofsky 80% or above
• Leukocytes \>= 3,000/uL
• Absolute neutrophil count \>= 1,500/uL
• Platelets \>= 100,000/uL
• Total bilirubin =\< 2.0 mg/dL
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.0 X institutional ULN
• Creatinine =\< 1 X institutional ULN

You may not qualify if:

• Women diagnosed with osteoporosis (previously or on screening dual-energy X-ray absorptiometry \[DEXA\] for this study) and not on a stable dose of long or short-acting bisphosphonates therapy for at least 3 months will be excluded from the study; women diagnosed with osteoporosis and on raloxifene (Evista) therapy will be excluded from the study; use of calcium and/or vitamin D for osteoporosis prevention or treatment is allowed; women with osteopenia will be allowed to participate in this study
• Have had invasive cancer within the past five years except non-melanoma skin cancer
• Evidence of suspicious of malignant disease on bilateral mammogram within the past year unless ruled out by further evaluation
• History of prior invasive breast cancer or intraductal carcinoma in situ, or history of prior radiation therapy to the chest or breast
• Participants may not be receiving any other investigational agents; participants may not be concurrently enrolled in another breast cancer prevention intervention trial
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to letrozole
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Within 3 months since prior estrogen or progesterone replacement therapy, oral contraceptives, androgens, luteinizing hormone-releasing hormone analogs, prolactin inhibitors, or antiandrogens
• Within 3 months since prior tamoxifen, raloxifene, or other selective estrogen-receptor modulators
• Within 3 months since regular use (more than 2 times a week) of prior estrogenic supplements or herbal remedies
• History of bleeding or clotting disorder; current or recent (within 3 months) use of Coumadin, Plavix or other systemic anticoagulant other than aspirin is not permitted if subject chooses to participate in the optional RPFNA procedure; if a subject chooses not to participate in the RPFNA procedure, prior or current treatment with systemic anticoagulants is permitted

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

Arizona Cancer Center - Tucson

Tucson, Arizona, 85724-5024, United States

Location

University of Arizona Health Sciences Center

Tucson, Arizona, 85724, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• Lopez AM, Pruthi S, Boughey JC, Perloff M, Hsu CH, Lang JE, Ley M, Frank D, Taverna JA, Chow HH. Double-Blind, Randomized Trial of Alternative Letrozole Dosing Regimens in Postmenopausal Women with Increased Breast Cancer Risk. Cancer Prev Res (Phila). 2016 Feb;9(2):142-8. doi: 10.1158/1940-6207.CAPR-15-0322. Epub 2015 Dec 14.

  PMID: 26667449 DERIVED

MeSH Terms

Conditions

Breast Carcinoma In Situ

Interventions

Letrozole

Condition Hierarchy (Ancestors)

Carcinoma in Situ; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Breast Neoplasms; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Ana Lopez

  University of Arizona Health Sciences Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2010
• First Posted: March 1, 2010
• Study Start: March 1, 2010
• Primary Completion: June 1, 2014
• Last Updated: October 20, 2014

Record last verified: 2014-10

Locations

US (3)