Letrozole in Preventing Breast Cancer in Postmenopausal Women

NCT00090857 | Completed Phase 2 Results DMC

• 4 other identifiers: DFCI-00024P50CA089393P30CA006516UCLA-0210012-02
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 5

Brief Summary

RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. Letrozole may be effective in preventing the development or recurrence of breast cancer in postmenopausal women who are at increased risk of developing breast cancer because of elevated estradiol levels. PURPOSE: This randomized phase II trial is studying how well letrozole works in preventing breast cancer in postmenopausal women with elevated estradiol levels.

Conditions

Breast Cancer

Keywords

breast cancer; stage I breast cancer; stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; stage IV breast cancer; breast cancer in situ; ductal breast carcinoma in situ

Outcome Measures

Primary Outcomes (4)

• Change in Lumbar Density From Baseline to 12 Months

  The bone mineral density (BMD) test was comprised of the following 4 measurements \[total density (g/cm\^2)\]: lumbar, femoral neck, trochanter, hip.

  Evaluation occurred at treatment initiation (BL) and after 12-months of treatment.

• Change in Femoral Neck Density From Baseline to 12 Months

  The bone mineral density (BMD) test was comprised of the following 4 measurements \[total density (g/cm\^2)\]: lumbar, femoral neck, trochanter, hip.

  Evaluation occurred at treatment initiation (BL) and after 12-months of treatment.

• Change in Trochanter Density From Baseline to 12 Months

  The bone mineral density (BMD) test was comprised of the following 4 measurements \[total density (g/cm\^2)\]: lumbar, femoral neck, trochanter, hip.

  Evaluation occurred at treatment initiation (BL) and after 12-months of treatment.

• Change in Hip Density From Baseline to 12 Months

  The bone mineral density (BMD) test was comprised of the following 4 measurements \[total density (g/cm\^2)\]: lumbar, femoral neck, trochanter, hip.

  Evaluation occurred at treatment initiation (BL) and after 12-months of treatment.

Secondary Outcomes (8)

• Worst Grade Hot Flashes

  Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.

• Worst Grade Muscle Aches/Pains

  Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.

• Worst Grade Nausea

  Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.

• Worst Grade Vomiting

  Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.

• Worst Grade Abdominal Pain

  Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.

Study Arms (2)

Letrozole

EXPERIMENTAL

Participants in this arm received 2.5 mg of letrozole per day for a duration of 12 months; followed by an optional 4 years. Treatment continued in the absence of unacceptable toxicity or diagnosis of invasive breast cancer, ductal carcinoma in situ, or any non-breast primary cancer.

Drug: Letrozole

Placebo

PLACEBO COMPARATOR

Participants in this arm received 1 tablet per day which contained the inert ingredients from the letrozole tablet, for a duration of 12 months; followed by an optional 5 years of letrozole.Treatment continued in the absence of unacceptable toxicity or diagnosis of invasive breast cancer, ductal carcinoma in situ, or any non-breast primary cancer.

Other: Placebo

Interventions

Letrozole DRUG

Also known as: Femara

Letrozole

Placebo OTHER

Placebo

Eligibility Criteria

• Age: 35 Years - 120 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * At increased risk for the development or recurrence of breast cancer, defined as an estradiol level ≥ 9 pg/mL * No evidence of suspicious or malignant disease, based on the following examinations: * Clinical bilateral breast examination within the past 6 months * Bilateral\* mammogram within 3 months before randomization OR within 30 days after randomization * Pelvic exam normal within the past 5 years * General physical exam within the past 6 months NOTE: \*Unilateral mammogram of the uninvolved breast for patients with prior invasive breast cancer or ductal carcinoma in situ (DCIS) * Bone density scan within 2 standard deviations from normal within the past 30 days * Bone density scan ≥ 2 standard deviations below normal allowed if approved by the study physician * At least 1 breast that has not been previously treated with radiotherapy or surgery (for patients with prior invasive breast cancer or DCIS) * Hormone receptor status: * Not specified PATIENT CHARACTERISTICS: Age * 35 and over Sex * Female Menopausal status * Postmenopausal, defined by any of the following criteria: * At least 12 months without spontaneous menstrual bleeding * Prior hysterectomy and bilateral salpingo-oophorectomy * ≥ 55 years of age with a prior hysterectomy with or without oophorectomy * \< 55 years of age with a prior hysterectomy without oophorectomy OR the status of the ovaries is unknown AND follicle-stimulating hormone (FSH) level is in the postmenopausal range Performance status * Normal activity must not be restricted for a significant portion of the day Life expectancy * At least 10 years Hematopoietic * Complete blood count with differential normal * Prior benign neutropenia allowed provided the granulocyte count is ≥ 1,500/mm\^3 Hepatic * Bilirubin normal * Alkaline phosphatase normal * SGOT and SGPT normal Renal * Creatinine normal Cardiovascular * No uncontrolled cardiovascular disease Other * Not pregnant * No other malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix * No osteoporosis * No hyperlipidemia * No mental health status resulting in cognitive or emotional impairment that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * Not specified Endocrine therapy * More than 30 days since prior AND no concurrent use of any of the following hormonal agents: * Estrogen or progesterone replacement therapy * Oral contraceptives * Raloxifene or other plasma estrogen receptor modulators (SERMs) * Androgens (e.g., danazol) * Luteinizing hormone-releasing hormone (LHRH) analogs (e.g., goserelin or leuprolide) * Prolactin inhibitors (e.g., bromocriptine) * Antiandrogens (e.g., cyproterone) * More than 60 days since prior AND no concurrent tamoxifen * No prior aromatase inhibitors (for patients with prior invasive breast cancer or DCIS) * No concurrent phytoestrogenic dietary supplements (e.g., soy, ginseng, or other natural products) * Dietary soy allowed Radiotherapy * See Disease Characteristics Surgery * See Disease Characteristics * No prior bilateral mastectomy Other * More than 60 days since prior treatment for invasive breast cancer or DCIS * More than 30 days since prior bisphosphonates or calcitonin * No prior or concurrent participation on a treatment study for invasive breast cancer or DCIS * No concurrent participation in any other cancer prevention study or osteoporosis prevention study involving pharmacologic agents * No concurrent calcitonin * No concurrent bisphosphonate therapy * Concurrent cholecalciferol (vitamin D) and calcium to augment bone mineral density allowed

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• National Cancer Institute (NCI): collaborator
• Jonsson Comprehensive Cancer Center: collaborator

Study Sites (5)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104-4283, United States

Location

Dan L. Duncan Cancer Center at Baylor College of Medicine

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Breast Carcinoma In Situ; Carcinoma, Intraductal, Noninfiltrating

Interventions

Letrozole

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

Results on this study are limited due to the age of the trial and the prior departure of the coordinator who assisted with the data collection. The accrual goal was not met with many participants eligible upon screening declining randomization.

Results Point of Contact

• Title: Judy E. Garber, MD, MPH
• Organization: Dana-Farber Cancer Institute

Judy_Garber@dfci.harvard.edu

617.632.2282

Study Officials

• Judy Garber, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

• Patricia A. Ganz, MD

  Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Garber, Judith MD

Study Record Dates

• First Submitted: September 7, 2004
• First Posted: September 8, 2004
• Study Start: February 1, 2002
• Primary Completion: August 1, 2008
• Study Completion: March 1, 2013
• Last Updated: March 30, 2018
• Results First Posted: June 29, 2017

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)