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Phase I Dose-Finding Trial of Letrozole in Postmenopausal Women at High Risk for Breast Cancer


Phase 1
35 Years
54 Years
Open (Enrolling)
Female
Lobular Breast Carcinoma in Situ

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Trial Information

Phase I Dose-Finding Trial of Letrozole in Postmenopausal Women at High Risk for Breast Cancer


PRIMARY OBJECTIVES:

I. The primary objective of this clinical trial is to compare the effect of lower and
intermittent doses of letrozole to standard letrozole therapy on estrogen suppression in
postmenopausal women at high risk for developing breast cancer.

SECONDARY OBJECTIVES:

I. Comparison of the effect of lower and intermittent doses of letrozole to standard therapy
on signs and symptoms of estrogen deficiency, including menopausal symptoms, serum lipid
profile, and serum marker of bone turnover.

II. Comparison of the effect of lower and intermittent doses of letrozole to standard
therapy on nuclear chromatin abnormality of breast epithelial cells collected by random
periareolar fine needle aspiration (RPFNA).

TERTIARY OBJECTIVES:

I. Determine the prevalence of breast cancer stem cells in the fine needle breast aspirates
and explore the potential intervention effect on the prevalence of breast cancer stem cells.

OUTLINE: Patients are randomized to 1 of 4 treatment arms.

ARM I: Patients receive 2.5 mg of letrozole orally (PO) thrice weekly for 6 months.

ARM II: Patients receive 1.0 mg of letrozole PO thrice weekly for 6 months.

ARM III: Patients receive 0.25 mg of letrozole PO thrice weekly for 6 months.

ARM IV: Patients receive 2.5 mg of letrozole PO once daily for 6 months.

After completion of study treatment, patients are followed up at week 30.


Inclusion Criteria:



- Healthy postmenopausal women at "high risk" for breast cancer will be eligible for
the study; definition of menopause will be:

- Amenorrhea for at least 12 months, or

- History of hysterectomy and bilateral salpingo-oophorectomy, or

- At least 55 years of age with prior hysterectomy with or without oophorectomy,
or

- Age 35 to 54 with a prior hysterectomy without oophorectomy OR with a status of
ovaries unknown with documented follicle-stimulating hormone level demonstrating
elevation in postmenopausal range

- "High risk" for breast cancer will be defined as:

- Prior histologically confirmed lobular carcinoma in situ (LCIS) treated by
local excision only, or

- At least 1.66% probability of invasive breast cancer within 5 years using
the Breast Cancer Risk Assessment Tool (http://www.cancer.gov/bcrisktool/)

- ECOG performance status 0 or 1 Karnofsky 80% or above

- Leukocytes >= 3,000/uL

- Absolute neutrophil count >= 1,500/uL

- Platelets >= 100,000/uL

- Total bilirubin =< 2.0 mg/dL

- AST (SGOT)/ALT (SGPT) =< 2.0 X institutional ULN

- Creatinine =< 1 X institutional ULN

- Recent mammogram negative for breast cancer, BIRADS score < 3 (within the last 12
months)

- Ability to understand and the willingness to sign a written informed consent
document; only potential participants with the ability to understand and the
willingness to sign a written document will be presented with an informed consenting
document

Exclusion Criteria:

- Women diagnosed with osteoporosis (previously or on screening DEXA for this study)
and not on a stable dose of long or short-acting bisphosphonates therapy for at least
3 months will be excluded from the study; women diagnosed with osteoporosis and on
raloxifene (Evista) therapy will be excluded from the study; use of calcium and/or
vitamin D for osteoporosis prevention or treatment is allowed; women with osteopenia
will be allowed to participate in this study

- Have had invasive cancer within the past five years except non-melanoma skin cancer

- Evidence of suspicious of malignant disease on bilateral mammogram within the past
year unless ruled out by further evaluation

- History of prior invasive breast cancer or intraductal carcinoma in situ, or history
of prior radiation therapy to the chest or breast

- Participants may not be receiving any other investigational agents; participants may
not be concurrently enrolled in another breast cancer prevention intervention trial

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to letrozole

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Within 3 months since prior estrogen or progesterone replacement therapy, oral
contraceptives, androgens, luteinizing hormone-releasing hormone analogs, prolactin
inhibitors, or antiandrogens

- Within 3 months since prior tamoxifen, raloxifene, or other selective
estrogen-receptor modulators

- Within 3 months since regular use (more than 2 times a week) of prior estrogenic
supplements or herbal remedies

- History of bleeding or clotting disorder; current or recent (within 3 months) use of
Coumadin, Plavix or other systemic anticoagulant other than aspirin is not permitted
if subject chooses to participate in the optional RPFNA procedure; if a subject
chooses not to participate in the RPFNA procedure, prior or current treatment with
systemic anticoagulants is permitted

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Outcome Measure:

Percentage of serum estradiol suppression in postmenopausal women at high risk for breast cancer

Outcome Description:

Three one-sided two-sample t-tests will be conducted on the ratios of the mean percentage of suppression simultaneously to test for non-inferiority. A multivariate t-distribution is used to derive the critical value and the power.

Outcome Time Frame:

Up to week 30

Safety Issue:

No

Principal Investigator

Ana Lopez

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Arizona Health Sciences Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2013-00757

NCT ID:

NCT01077453

Start Date:

March 2010

Completion Date:

Related Keywords:

  • Lobular Breast Carcinoma in Situ
  • Breast Neoplasms
  • Carcinoma
  • Carcinoma in Situ
  • Carcinoma, Lobular

Name

Location

Mayo ClinicRochester, Minnesota  55905
University of Arizona Health Sciences CenterTucson, Arizona  85724