| ID | Type | Description | Link |
|---|---|---|---|
| P50CA089393 | U.S. NIH Grant/Contract | View source | |
| P30CA006516 | U.S. NIH Grant/Contract | View source | |
| DFCI-00024 | |||
| UCLA-0210012-02 |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
| Jonsson Comprehensive Cancer Center | OTHER |
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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.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a pilot, randomized, double-blind, placebo-controlled, multicenter study. Patients are randomized to 2:1 (experimental treatment: placebo arms).
PROJECTED ACCRUAL: A total of 110 patients (73 for arm I and 37 for arm II) will be accrued for this study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Letrozole | Drug |
|
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Worst Grade Hot Flashes | Participants reported worst grade hot flashes: 01: mild (<1qd) or 02: moderate (>1qd) during 12 months of treatment. | 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 |
Not provided
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:
Bone density scan within 2 standard deviations from normal within the past 30 days
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:
PATIENT CHARACTERISTICS:
Age
Sex
Menopausal status
Postmenopausal, defined by any of the following criteria:
Performance status
Life expectancy
Hematopoietic
Complete blood count with differential normal
Hepatic
Renal
Cardiovascular
Other
PRIOR CONCURRENT THERAPY:
Biologic therapy
Chemotherapy
Endocrine therapy
More than 30 days since prior AND no concurrent use of any of the following hormonal agents:
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)
Radiotherapy
Surgery
Other
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| Name | Affiliation | Role |
|---|---|---|
| Judy Garber, MD | Dana-Farber Cancer Institute | Principal Investigator |
| Patricia A. Ganz, MD | Jonsson Comprehensive Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States | ||
| Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute |
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In this chemoprevention trial, postmenopausal women were screened and eligible based on serum estradiol levels. Of 405 women screened, 381 were eligible for blood draw. Of these 381 women eligible for blood draw, 87 were eligible for randomization based on serum estradiol level (>/=0.9 ng/dL). There were 38 women who declined to be randomized.
Patients enrolled from February 2002 through August 2007.
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| ID | Title | Description |
|---|---|---|
| FG000 | Letrozole | 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. |
| FG001 | Placebo | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Letrozole | 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. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| 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 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. | The analysis dataset is comprised of randomized patients with an evaluable sample for analysis of lumbar density. | Posted | Median | Full Range | g/cm^2 | Evaluation occurred at treatment initiation (BL) and after 12-months of treatment. |
|
Adverse events were evaluated and reported on the case report forms while participants were on randomized treatment at each clinic follow-up visit (months 6 and 12). If participants opted to continue treatment beyond 12 months then adverse events were monitored annually. Relevant for this report were the adverse events associated with the planned 12 months of treatment. 86% of patients in this study cohort completed 12 months of randomized treatment (median treatment duration is 12 months).
Serious adverse events (SAEs) per protocol were defined as follows: 1) death, 2) a life-threatening adverse drug experience, 3) inpatient hospitalization or prolongation of existing hospitalization, 4) a persistent or significant disability/incapacity, or 5) a congenital anomaly/birth defect. All remaining AEs are Other AEs. Of note, secondary outcome measures 5-12 provide data on pre-specified analyses of key symptoms pertaining to use of the experimental treatment.
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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 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pain - Head/Headache | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Arthritis (non-septic) | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Judy E. Garber, MD, MPH | Dana-Farber Cancer Institute | 617.632.2282 | Judy_Garber@dfci.harvard.edu |
Not provided
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D000071960 | Breast Carcinoma In Situ |
| D002285 | Carcinoma, Intraductal, Noninfiltrating |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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Not provided
| ID | Term |
|---|---|
| D000077289 | Letrozole |
| ID | Term |
|---|---|
| D009570 | Nitriles |
| D009930 | Organic Chemicals |
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 |
Not provided
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| Other |
|
Participants reported worst grade muscle aches/pains defined as grade 01: mild, 02: moderate, 03: severe (CTCAEv3) or 04: disabling (CTCAEv3) during 12 months of treatment. |
| 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 | Participants reported worst grade nausea grade 01: able to eat, 02: oral intake significantly decreased, 03: no significant intake, requiring IV fluids during 12 months of treatment. | 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 | Participants reported worst grade vomiting grade 01: 1x in 24 hours, 02: 2-5x in 24 hours, 03: >/= 6x in 24 hours, grade 04: requiring parenteral nutrition/intensive care during 12 months of treatment. | 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 | Participants reported worst grade abdominal pain: 01: mild, 02: moderate, 03: severe (CTCAEv3), 04: disabling (CTCAEv3) during 12 months of treatment. | Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months. |
| Worst Grade Bone Pain | Participants reported worst grade bone pain: 01: mild, 02: moderate, 03: severe (CTCAEv3), 04: disabling (CTCAEv3) during 12 months of treatment. | Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months. |
| Worst Grade Headache | Participants reported worst grade headache: 01: mild, 02: moderate, 03: severe (CTCAEv3), 04: disabling (CTCAEv3) during 12 months of treatment. | Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months. |
| Worst Grade Fatigue | Participants reported worst grade fatigue: 01: mild, 02: moderate, 03: severe (CTCAEv3), 04: disabling (CTCAEv3) during 12 months of treatment. | Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months. |
| Boston |
| Massachusetts |
| 02115 |
| United States |
| Beth Israel Deaconess Medical Center | Boston | Massachusetts | 02215 | United States |
| Abramson Cancer Center of the University of Pennsylvania | Philadelphia | Pennsylvania | 19104-4283 | United States |
| Dan L. Duncan Cancer Center at Baylor College of Medicine | Houston | Texas | 77030 | United States |
| Adverse Event |
|
| Placebo |
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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Placebo |
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. |
|
|
|
| Primary | 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. | The analysis dataset is comprised of randomized patients with an evaluable sample for analysis of femoral neck density. | Posted | Median | Full Range | g/cm^2 | Evaluation occurred at treatment initiation (BL) and after 12-months of treatment. |
|
|
|
|
| Primary | 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. | The analysis dataset is comprised of randomized patients with an evaluable sample for analysis of trochanter density. | Posted | Median | Full Range | g/cm^2 | Evaluation occurred at treatment initiation (BL) and after 12-months of treatment. |
|
|
|
|
| Primary | 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. | The analysis dataset is comprised of randomized patients with an evaluable sample for analysis of hip density. | Posted | Median | Full Range | g/cm^2 | Evaluation occurred at treatment initiation (BL) and after 12-months of treatment. |
|
|
|
|
| Secondary | Worst Grade Hot Flashes | Participants reported worst grade hot flashes: 01: mild (<1qd) or 02: moderate (>1qd) during 12 months of treatment. | The analysis dataset is comprised of all randomized participants. | Posted | Count of Participants | Participants | Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months. |
|
|
|
|
| Secondary | Worst Grade Muscle Aches/Pains | Participants reported worst grade muscle aches/pains defined as grade 01: mild, 02: moderate, 03: severe (CTCAEv3) or 04: disabling (CTCAEv3) during 12 months of treatment. | Posted | Count of Participants | Participants | Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months. |
|
|
|
|
| Secondary | Worst Grade Nausea | Participants reported worst grade nausea grade 01: able to eat, 02: oral intake significantly decreased, 03: no significant intake, requiring IV fluids during 12 months of treatment. | The analysis dataset is comprised of all randomized participants. | Posted | Count of Participants | Participants | Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months. |
|
|
|
|
| Secondary | Worst Grade Vomiting | Participants reported worst grade vomiting grade 01: 1x in 24 hours, 02: 2-5x in 24 hours, 03: >/= 6x in 24 hours, grade 04: requiring parenteral nutrition/intensive care during 12 months of treatment. | The analysis dataset is comprised of all randomized participants. | Posted | Count of Participants | Participants | Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months. |
|
|
|
|
| Secondary | Worst Grade Abdominal Pain | Participants reported worst grade abdominal pain: 01: mild, 02: moderate, 03: severe (CTCAEv3), 04: disabling (CTCAEv3) during 12 months of treatment. | The analysis dataset is comprised of all randomized participants. | Posted | Count of Participants | Participants | Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months. |
|
|
|
|
| Secondary | Worst Grade Bone Pain | Participants reported worst grade bone pain: 01: mild, 02: moderate, 03: severe (CTCAEv3), 04: disabling (CTCAEv3) during 12 months of treatment. | Posted | Count of Participants | Participants | Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months. |
|
|
|
|
| Secondary | Worst Grade Headache | Participants reported worst grade headache: 01: mild, 02: moderate, 03: severe (CTCAEv3), 04: disabling (CTCAEv3) during 12 months of treatment. | Posted | Count of Participants | Participants | Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months. |
|
|
|
|
| Secondary | Worst Grade Fatigue | Participants reported worst grade fatigue: 01: mild, 02: moderate, 03: severe (CTCAEv3), 04: disabling (CTCAEv3) during 12 months of treatment. | Posted | Count of Participants | Participants | Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months. |
|
|
|
|
| 0 |
| 33 |
| 1 |
| 33 |
| 6 |
| 33 |
| EG001 | Placebo | 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. | 0 | 16 | 0 | 16 | 2 | 16 |
| Urticaria (hives, welts, wheals) | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pruritus / Itching | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain - Muscle | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Vaginitis (not due to infection) | Reproductive system and breast disorders | CTCAE (3.0) | Systematic Assessment |
|
| Vasovagal episode | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Weight gain | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Fatigue (asthenia, lethargy, malaise) | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hot flashes/flushes | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain - Chest/thorax NOS | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dyspnea (shortness of breath) | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
Not provided
Not provided
| D017437 |
| Skin and Connective Tissue Diseases |
| D002278 | Carcinoma in Situ |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D000230 | Adenocarcinoma |
| D018299 | Neoplasms, Ductal, Lobular, and Medullary |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| Moderate |
|
| Missing |
|
| Moderate |
|
| Severe |
|
| Missing |
|
| Oral Intake Significantly Decreased |
|
| Missing |
|
| 2-5x in 24 hours |
|
| Missing |
|
| Missing |
|
| Moderate |
|
| Missing |
|
| Moderate |
|
| Missing |
|
| Moderate |
|
| Missing |
|