Letrozole in Preventing Breast Cancer in Postmenopausal Women (WISE)
A Pilot Study of Aromatase Inhibitors for Women at Increased Risk of Breast Cancer Based on Estradiol Levels
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.
調査の概要
詳細な説明
OBJECTIVES:
Primary
- The primary outcome of the study is the change in bone mineral density following a year on letrozole vs. a year on placebo.
Secondary
- Compare the safety, acceptability, and adherence to letrozole vs placebo in postmenopausal women at increased risk for the development or recurrence of breast cancer based on elevated plasma estradiol levels through evaluation of menopausal symptoms (including hot flushes, weight changes, sexual functioning, and genitourinary effects), blood lipid levels, markers of bone turnover, and multidimensional quality of life.
- Determine the effect of letrozole-induced reduction of plasma estradiol levels on mammographic percent breast density.
- Obtain background information for a future large chemoprevention trial to address the question of whether a reduction in plasma estradiol levels can reduce the risk of breast cancer in postmenopausal women.
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.
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
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Massachusetts
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Boston、Massachusetts、アメリカ、02215
- Beth Israel Deaconess Medical Center
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Boston、Massachusetts、アメリカ、02114
- Massachusetts General Hospital
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Boston、Massachusetts、アメリカ、02115
- Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
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Pennsylvania
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Philadelphia、Pennsylvania、アメリカ、19104-4283
- Abramson Cancer Center of the University of Pennsylvania
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Texas
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Houston、Texas、アメリカ、77030
- Dan L. Duncan Cancer Center at Baylor College of Medicine
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:防止
- 割り当て:ランダム化
- 介入モデル:並列代入
- マスキング:ダブル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的: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.
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他の名前:
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プラセボコンパレーター: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.
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この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Change in Lumbar Density From Baseline to 12 Months
時間枠:Evaluation occurred at treatment initiation (BL) and after 12-months of treatment.
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The bone mineral density (BMD) test was comprised of the following 4 measurements [total density (g/cm^2)]: lumbar, femoral neck, trochanter, hip.
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Evaluation occurred at treatment initiation (BL) and after 12-months of treatment.
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Change in Femoral Neck Density From Baseline to 12 Months
時間枠:Evaluation occurred at treatment initiation (BL) and after 12-months of treatment.
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The bone mineral density (BMD) test was comprised of the following 4 measurements [total density (g/cm^2)]: lumbar, femoral neck, trochanter, hip.
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Evaluation occurred at treatment initiation (BL) and after 12-months of treatment.
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Change in Trochanter Density From Baseline to 12 Months
時間枠:Evaluation occurred at treatment initiation (BL) and after 12-months of treatment.
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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.
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Change in Hip Density From Baseline to 12 Months
時間枠:Evaluation occurred at treatment initiation (BL) and after 12-months of treatment.
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The bone mineral density (BMD) test was comprised of the following 4 measurements [total density (g/cm^2)]: lumbar, femoral neck, trochanter, hip.
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Evaluation occurred at treatment initiation (BL) and after 12-months of treatment.
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Worst Grade Hot Flashes
時間枠:Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
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Participants reported worst grade hot flashes: 01: mild (<1qd) or 02: moderate (>1qd) during 12 months of treatment.
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Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
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Worst Grade Muscle Aches/Pains
時間枠:Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
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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.
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Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
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Worst Grade Nausea
時間枠:Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
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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.
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Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
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Worst Grade Vomiting
時間枠:Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
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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.
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Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
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Worst Grade Abdominal Pain
時間枠:Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
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Participants reported worst grade abdominal pain: 01: mild, 02: moderate, 03: severe (CTCAEv3), 04: disabling (CTCAEv3) during 12 months of treatment.
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Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
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Worst Grade Bone Pain
時間枠:Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
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Participants reported worst grade bone pain: 01: mild, 02: moderate, 03: severe (CTCAEv3), 04: disabling (CTCAEv3) during 12 months of treatment.
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Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
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Worst Grade Headache
時間枠:Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
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Participants reported worst grade headache: 01: mild, 02: moderate, 03: severe (CTCAEv3), 04: disabling (CTCAEv3) during 12 months of treatment.
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Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
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Worst Grade Fatigue
時間枠:Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
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Participants reported worst grade fatigue: 01: mild, 02: moderate, 03: severe (CTCAEv3), 04: disabling (CTCAEv3) during 12 months of treatment.
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Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
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協力者と研究者
捜査官
- 主任研究者:Judy Garber, MD、Dana-Farber Cancer Institute
- 主任研究者:Patricia A. Ganz, MD、Jonsson Comprehensive Cancer Center
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- DFCI-00024
- P50CA089393 (米国 NIH グラント/契約)
- P30CA006516 (米国 NIH グラント/契約)
- UCLA-0210012-02
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
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