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Letrozole in Preventing Breast Cancer in Postmenopausal Women (WISE)

5 de março de 2018 atualizado por: Judy E. Garber, MD, Dana-Farber Cancer Institute

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

Concluído

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

Intervencional

Inscrição (Real)

49

Estágio

  • Fase 2

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

    • Massachusetts
      • Boston, Massachusetts, Estados Unidos, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, Estados Unidos, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, Estados Unidos, 02115
        • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
    • Pennsylvania
      • Philadelphia, Pennsylvania, Estados Unidos, 19104-4283
        • Abramson Cancer Center of the University of Pennsylvania
    • Texas
      • Houston, Texas, Estados Unidos, 77030
        • Dan L. Duncan Cancer Center at Baylor College of Medicine

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

35 anos a 120 anos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Fêmea

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

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

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
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.
Outros nomes:
  • Femara
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.

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Change in Lumbar Density From Baseline to 12 Months
Prazo: Evaluation occurred at treatment initiation (BL) and after 12-months of treatment.
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
Prazo: Evaluation occurred at treatment initiation (BL) and after 12-months of treatment.
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
Prazo: Evaluation occurred at treatment initiation (BL) and after 12-months of treatment.
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
Prazo: Evaluation occurred at treatment initiation (BL) and after 12-months of treatment.
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.

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
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.
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
Prazo: Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
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
Prazo: Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
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
Prazo: Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
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
Prazo: Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
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
Prazo: Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
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
Prazo: Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
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
Prazo: Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
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.

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

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

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

1 de fevereiro de 2002

Conclusão Primária (Real)

1 de agosto de 2008

Conclusão do estudo (Real)

1 de março de 2013

Datas de inscrição no estudo

Enviado pela primeira vez

7 de setembro de 2004

Enviado pela primeira vez que atendeu aos critérios de CQ

7 de setembro de 2004

Primeira postagem (Estimativa)

8 de setembro de 2004

Atualizações de registro de estudo

Última Atualização Postada (Real)

30 de março de 2018

Última atualização enviada que atendeu aos critérios de controle de qualidade

5 de março de 2018

Última verificação

1 de março de 2018

Mais Informações

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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