Clinical trial NCT00090857: Letrozole in Preventing Breast Cancer in Postmenopausal Women
Official title: A Pilot Study of Aromatase Inhibitors for Women at Increased Risk of Breast Cancer Based on Estradiol Levels
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: 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
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Jonsson Comprehensive Cancer Center
First posted: 2004-09-08
Enrollment: 49
Sex: FEMALE
Minimum age (years): 35
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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 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

Primary outcomes:
measure: Change in Lumbar Density From Baseline to 12 Months
timeFrame: Evaluation occurred at treatment initiation (BL) and after 12-months of treatment.
measure: Change in Femoral Neck Density From Baseline to 12 Months
timeFrame: Evaluation occurred at treatment initiation (BL) and after 12-months of treatment.
measure: Change in Trochanter Density From Baseline to 12 Months
timeFrame: Evaluation occurred at treatment initiation (BL) and after 12-months of treatment.
measure: Change in Hip Density From Baseline to 12 Months
timeFrame: Evaluation occurred at treatment initiation (BL) and after 12-months of treatment.
Secondary outcomes:
measure: Worst Grade Hot Flashes
timeFrame: Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
measure: Worst Grade Muscle Aches/Pains
timeFrame: Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
measure: Worst Grade Nausea
timeFrame: Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
measure: Worst Grade Vomiting
timeFrame: Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
measure: Worst Grade Abdominal Pain
timeFrame: Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
measure: Worst Grade Bone Pain
timeFrame: Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
measure: Worst Grade Headache
timeFrame: Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
measure: Worst Grade Fatigue
timeFrame: Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
city: Houston
country: United States
facility: Dan L. Duncan Cancer Center at Baylor College of Medicine
state: Texas
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Judy Garber, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Jonsson Comprehensive Cancer Center
name: Patricia A. Ganz, MD
role: PRINCIPAL_INVESTIGATOR
References: