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| ID | Type | Description | Link |
|---|---|---|---|
| CFEM345AUS45 | Other Grant/Funding Number | Novartis | |
| 5R01CA122577-03 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Novartis | INDUSTRY |
| National Cancer Institute (NCI) | NIH |
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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.
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Letrozole | Experimental | Letrozole, 2.5 mg daily for 6 months |
|
| Placebo | Placebo Comparator | Placebo, daily for 6 months |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Letrozole | Drug | Letrozole 2.5 mg tablet daily. Then optional open label letrozole for another 6 months. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Proliferation Rate (Ki-67 by Immunocytochemistry) From Baseline to 6 Months | Change in proliferation rate (percent positively stained cells for Ki-67 antigen by immunocytochemistry) in benign breast epithelial cells acquired by random periareolar fine needle aspiration (RPFNA) from women at high risk for the development of breast cancer. | Baseline to 6 Months |
| Measure | Description | Time Frame |
|---|---|---|
| Assessment of Change in Morphology by the Masood Score. | Masood score is a semi-quantitative index of increasing abnormality, thus higher values are worse. Range 6 to 24. Based on Masood S, Frykberg ER, McLellan GL, Scalapino MC, Mitchum DG, Bullard JB. Prospective evaluation of radiologically directed fine-needle aspiration biopsy of nonpalpable breast lesions. Cancer 1990; 66:1480-7. | Baseline to 6 Months |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Fibromyalgia Impact Questionnaire (FIQ) Score. | Assessment of impact of fibromyalgia on everyday living activities. Composite score ranges from 0 (best, no interference or impact on activities) to 104 (worst, maximum interference with activities). | Baseline to 6 months |
| Change in Brief Fatigue Inventory (BFI) Score. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Carol J Fabian, MD | University of Kansas Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Kansas Medical Center | Kansas City | Kansas | 66160 | United States |
Global results will be published.
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| ID | Title | Description |
|---|---|---|
| FG000 | Letrozole | Letrozole, 2.5 mg daily for 6 months Letrozole: Letrozole 2.5 mg tablet daily. Then optional open label letrozole for another 6 months. |
| FG001 | Placebo | Placebo, daily for 6 months Placebo: Placebo tablet daily for 6 months then optional open label letrozole for 6 months. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All enrolled subjects
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| ID | Title | Description |
|---|---|---|
| BG000 | Letrozole | Letrozole, 2.5 mg daily for 6 months Letrozole: Letrozole 2.5 mg tablet daily. Then optional open label letrozole for another 6 months. |
| BG001 | Placebo | Placebo, daily for 6 months Placebo: Placebo tablet daily for 6 months then optional open label letrozole for 6 months. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Proliferation Rate (Ki-67 by Immunocytochemistry) From Baseline to 6 Months | Change in proliferation rate (percent positively stained cells for Ki-67 antigen by immunocytochemistry) in benign breast epithelial cells acquired by random periareolar fine needle aspiration (RPFNA) from women at high risk for the development of breast cancer. | Subjects who complete initial 6-month period and have repeat RPFNA. | Posted | Mean | Standard Deviation | percentage of cells stained positive | Baseline to 6 Months |
|
1 year
duration of study agent
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Letrozole, 2.5 mg Daily for 12 Months | Letrozole, 2.5 mg daily for 6 months Letrozole: Letrozole 2.5 mg tablet daily. Then optional open label letrozole for another 6 months. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cataract | Eye disorders | CTCAE 3.0 | Systematic Assessment | Grade 3 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Bruce F. Kimler, Ph.D. | University of Kansas Medical Center | 913-588-4523 | bkimler@kumc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 5, 2012 | Jan 6, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| D000077289 | Letrozole |
| ID | Term |
|---|---|
| D009570 | Nitriles |
| D009930 | Organic Chemicals |
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 |
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| Placebo | Drug | Placebo tablet daily for 6 months then optional open label letrozole for 6 months. |
|
| Change in Mammographic Density From Baseline to 6 Months.. | Percent area of the breast considered to be at increased density, as determined by the computer program Cumulus.. | Baseline to 6 Months |
Assessment of the extent to which fatigue interferes in normal everyday living activities. Change over 6 months of treatment is assessed. Range from 0 (best, no fatigue) to 10 (worst). Increase in score indicates greater intensity of fatigue and/or greater interference with activities due to fatigue. |
| baseline to 6 months |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Height | Mean | Standard Deviation | m |
|
| Weight | Mean | Standard Deviation | kg |
|
| Body Mass Index | Mean | Standard Deviation | kg/m^2 |
|
| Age at menarche | Mean | Standard Deviation | years |
|
| Age at first live birth | Mean | Standard Deviation | years |
|
| History of prior breast biopsy | Number | participants |
|
| History of prior Ductal Carcinoma In Situ (DCIS) or Lobular Carcinoma in Situ (LCIS) | Number | participants |
|
| Number of relatives with breast cancer | Number | participants |
|
| Gail risk of developing breast cancer within 5 years | Mean | Standard Deviation | percent |
|
| Immunocytochemical expression of Ki-67 | Percent of breast epithelial cells staining positive for Ki-67 by immunocytochemistry. | Mean | Standard Deviation | percent |
|
| Cytology | Number | participants |
|
| Masood Score | Semi-quantitative cytology index score reflecting increasing abnormality, thus higher scores are worse. Range 6 to 24. | Mean | Standard Deviation | units on a scale |
|
Placebo, daily for 6 months Placebo: Placebo tablet daily for 6 months then optional open label letrozole for 6 months. |
|
|
|
| Secondary | Assessment of Change in Morphology by the Masood Score. | Masood score is a semi-quantitative index of increasing abnormality, thus higher values are worse. Range 6 to 24. Based on Masood S, Frykberg ER, McLellan GL, Scalapino MC, Mitchum DG, Bullard JB. Prospective evaluation of radiologically directed fine-needle aspiration biopsy of nonpalpable breast lesions. Cancer 1990; 66:1480-7. | Subjects who complete initial 6-month intervention and have a repeat RPFNA, thus a change from baseline to 6-months can be computed. | Posted | Mean | Standard Deviation | units on a scale | Baseline to 6 Months |
|
|
|
|
| Secondary | Change in Mammographic Density From Baseline to 6 Months.. | Percent area of the breast considered to be at increased density, as determined by the computer program Cumulus.. | Subjects who complete the initial 6-months intervention and have mammograms available for analysis at baseline and 6 months, thus a change can be computed. | Posted | Mean | Standard Deviation | percent of breast area at high density | Baseline to 6 Months |
|
|
|
|
| Other Pre-specified | Change in Fibromyalgia Impact Questionnaire (FIQ) Score. | Assessment of impact of fibromyalgia on everyday living activities. Composite score ranges from 0 (best, no interference or impact on activities) to 104 (worst, maximum interference with activities). | subjects who complete 6 month visit and provide a 6-month FIQ score, such that the change in score (6-month - baseline) can be computed. | Posted | Mean | Standard Deviation | score on scale | Baseline to 6 months |
|
|
|
|
| Other Pre-specified | Change in Brief Fatigue Inventory (BFI) Score. | Assessment of the extent to which fatigue interferes in normal everyday living activities. Change over 6 months of treatment is assessed. Range from 0 (best, no fatigue) to 10 (worst). Increase in score indicates greater intensity of fatigue and/or greater interference with activities due to fatigue. | Subjects who complete a 6-months visit and a 6-months BFI questionnaire, such that change in score can be computed. | Posted | Mean | Standard Deviation | score on a scale | baseline to 6 months |
|
|
|
|
| 0 |
| 29 |
| 11 |
| 29 |
| EG001 | Placebo for 6 Months; Open Label Letrozole 2.5 mg Daily | Placebo, daily for 6 months Placebo: Placebo tablet daily for 6 months then optional open label letrozole for 6 months. | 0 | 26 | 3 | 26 |
| Musculoskeletal Pain | Musculoskeletal and connective tissue disorders | CTCAE 3.0 | Systematic Assessment | Grade 3 |
|
| Atrial Tachycardia | Cardiac disorders | CTCAE 3.0 | Systematic Assessment | Grade 3 |
|
| Wound complication | Skin and subcutaneous tissue disorders | CTCAE 3.0 | Systematic Assessment | Grade 3 |
|
| Gallbladder necrosis | Hepatobiliary disorders | CTCAE 3.0 | Systematic Assessment | Grade 3 |
|
| Kidney pain | Renal and urinary disorders | CTCAE 3.0 | Systematic Assessment | Grade 3 |
|
| Dizziness | Nervous system disorders | CTCAE 3.0 | Systematic Assessment | Grade 3 |
|
| Vomiting/nausea | Gastrointestinal disorders | CTCAE 3.0 | Systematic Assessment | Grade 3 |
|
| Headache | Nervous system disorders | CTCAE 3.0 | Systematic Assessment | Grade 3 |
|
| Vaginal mucositis/ cervical infection | Reproductive system and breast disorders | CTCAE 3.0 | Systematic Assessment | Grade 3 |
|
| Skin infection | Skin and subcutaneous tissue disorders | CTCAE 3.0 | Systematic Assessment | Grade 3 |
|
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| D017437 |
| Skin and Connective Tissue Diseases |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |