- ICH GCP
- Registro de ensaios clínicos dos EUA
- Ensaio Clínico NCT00090857
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.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
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.
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 2
Contactos e Locais
Locais de estudo
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02215
- Beth Israel Deaconess Medical Center
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Boston, Massachusetts, Estados Unidos, 02114
- Massachusetts General Hospital
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Boston, Massachusetts, Estados Unidos, 02115
- Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
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Pennsylvania
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Philadelphia, Pennsylvania, Estados Unidos, 19104-4283
- Abramson Cancer Center of the University of Pennsylvania
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Texas
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Houston, Texas, Estados Unidos, 77030
- Dan L. Duncan Cancer Center at Baylor College of Medicine
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
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
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Prevenção
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Dobro
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: 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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Outros nomes:
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Comparador de Placebo: 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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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Change in Lumbar Density From Baseline to 12 Months
Prazo: 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
Prazo: 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
Prazo: 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 Hip Density From Baseline to 12 Months
Prazo: 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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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Worst Grade Hot Flashes
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Judy Garber, MD, Dana-Farber Cancer Institute
- Investigador principal: Patricia A. Ganz, MD, Jonsson Comprehensive Cancer Center
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Doenças de pele
- Neoplasias
- Neoplasias por local
- Doenças da mama
- Neoplasias da Mama
- Efeitos Fisiológicos das Drogas
- Mecanismos Moleculares de Ação Farmacológica
- Inibidores Enzimáticos
- Agentes Antineoplásicos
- Hormônios, Substitutos Hormonais e Antagonistas Hormonais
- Antagonistas Hormonais
- Inibidores de Aromatase
- Inibidores da Síntese de Esteróides
- Antagonistas de Estrogênio
- Letrozol
Outros números de identificação do estudo
- DFCI-00024
- P50CA089393 (Concessão/Contrato do NIH dos EUA)
- P30CA006516 (Concessão/Contrato do NIH dos EUA)
- UCLA-0210012-02
Plano para dados de participantes individuais (IPD)
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