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Letrozole in Preventing Breast Cancer in Postmenopausal Women (WISE)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00090857
First Posted: September 8, 2004
Last Update Posted: June 29, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
National Cancer Institute (NCI)
Jonsson Comprehensive Cancer Center
Information provided by (Responsible Party):
Judy E. Garber, MD, Dana-Farber Cancer Institute
  Purpose

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.


Condition Intervention Phase
Breast Cancer Drug: Letrozole Other: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: A Pilot Study of Aromatase Inhibitors for Women at Increased Risk of Breast Cancer Based on Estradiol Levels

Resource links provided by NLM:


Further study details as provided by Judy E. Garber, MD, Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Change in Lumbar Density From Baseline to 12 Months [ Time Frame: 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.

  • Change in Femoral Neck Density From Baseline to 12 Months [ Time Frame: 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.

  • Change in Trochanter Density From Baseline to 12 Months [ Time Frame: 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.

  • Change in Hip Density From Baseline to 12 Months [ Time Frame: 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.


Secondary Outcome Measures:
  • Worst Grade Hot Flashes [ Time Frame: 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.

  • Worst Grade Muscle Aches/Pains [ Time Frame: 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.

  • Worst Grade Nausea [ Time Frame: 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.

  • Worst Grade Vomiting [ Time Frame: 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.

  • Worst Grade Abdominal Pain [ Time Frame: 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.

  • Worst Grade Bone Pain [ Time Frame: 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.

  • Worst Grade Headache [ Time Frame: 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.

  • Worst Grade Fatigue [ Time Frame: 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.


Enrollment: 49
Actual Study Start Date: February 2002
Study Completion Date: March 2013
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Letrozole
Other Name: Femara
Placebo Comparator: 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.
Other: Placebo

Detailed Description:

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   35 Years to 120 Years   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00090857


Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104-4283
United States, Texas
Dan L. Duncan Cancer Center at Baylor College of Medicine
Houston, Texas, United States, 77030
Sponsors and Collaborators
Dana-Farber Cancer Institute
National Cancer Institute (NCI)
Jonsson Comprehensive Cancer Center
Investigators
Principal Investigator: Judy Garber, MD Dana-Farber Cancer Institute
Principal Investigator: Patricia A. Ganz, MD Jonsson Comprehensive Cancer Center
  More Information

Responsible Party: Judy E. Garber, MD, Garber, Judith MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00090857     History of Changes
Obsolete Identifiers: NCT00165529, NCT00577551
Other Study ID Numbers: DFCI-00024
P50CA089393 ( U.S. NIH Grant/Contract )
P30CA006516 ( U.S. NIH Grant/Contract )
UCLA-0210012-02
First Submitted: September 7, 2004
First Posted: September 8, 2004
Results First Submitted: January 18, 2017
Results First Posted: June 29, 2017
Last Update Posted: June 29, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Judy E. Garber, MD, Dana-Farber Cancer Institute:
breast cancer
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer
breast cancer in situ
ductal breast carcinoma in situ

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs