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Letrozole in Preventing Breast Cancer in Postmenopausal Women (WISE)

5. mars 2018 oppdatert av: 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.

Studieoversikt

Status

Fullført

Forhold

Detaljert beskrivelse

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.

Studietype

Intervensjonell

Registrering (Faktiske)

49

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

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

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

35 år til 120 år (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Hunn

Beskrivelse

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

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Forebygging
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Dobbelt

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: 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.
Andre navn:
  • Femara
Placebo komparator: 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.

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Change in Lumbar Density From Baseline to 12 Months
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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.

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Worst Grade Hot Flashes
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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.

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Etterforskere

  • Hovedetterforsker: Judy Garber, MD, Dana-Farber Cancer Institute
  • Hovedetterforsker: Patricia A. Ganz, MD, Jonsson Comprehensive Cancer Center

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

1. februar 2002

Primær fullføring (Faktiske)

1. august 2008

Studiet fullført (Faktiske)

1. mars 2013

Datoer for studieregistrering

Først innsendt

7. september 2004

Først innsendt som oppfylte QC-kriteriene

7. september 2004

Først lagt ut (Anslag)

8. september 2004

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

30. mars 2018

Siste oppdatering sendt inn som oppfylte QC-kriteriene

5. mars 2018

Sist bekreftet

1. mars 2018

Mer informasjon

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