Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer

NCT ID: NCT00253539

Last Updated: 2011-04-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-01-31
• Study Completion Date: 2005-04-30

Brief Summary

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. Estrogen can cause the growth of breast cancer cells. Hormone therapy using arzoxifene or tamoxifen may prevent breast cancer by lowering the amount of estrogen the body makes. The use of arzoxifene or tamoxifen may keep breast cancer from forming in women at high risk for breast cancer.

PURPOSE: This randomized phase II trial is studying arzoxifene to see how well it works compared to tamoxifen or a placebo in preventing breast cancer in premenopausal women at high risk for breast cancer.

Detailed Description

OBJECTIVES:

• Compare the effect of arzoxifene vs tamoxifen vs placebo on surrogate endpoints biomarkers, especially systemic insulin-like growth factor levels, in women at high risk for breast cancer.
• Compare the toxic effects, biologic effects, clinical pharmacology, and pharmacodynamics of these drugs in these participants.
• Determine the effect of these drugs on surrogate endpoint biomarkers in participants with BRCA1 and BRCA2 mutations.
• Determine the feasibility of a chemoprevention study in participants with a strong family history of breast cancer.

OUTLINE: This is a randomized, placebo-controlled, double-blind study. Participants are randomized to 1 of 3 treatment arms.

• Arm I: Participants receive oral tamoxifen once daily.
• Arm II: Participants receive oral arzoxifene once daily.
• Arm III: Participants receive an oral placebo once daily. In all arms, treatment continues for 6 months in the absence of disease progression or unacceptable toxicity. After the completion of 6 months of treatment, participants are offered the opportunity to continue treatment with their assigned study drug for an additional 6 months. Participants randomized to receive placebo are offered treatment with arzoxifene for an additional 6 months.

After completion of study treatment, participants are followed annually.

PROJECTED ACCRUAL: A total of 120 participants will be accrued for this study.

Conditions

Breast Cancer; Hereditary Breast/Ovarian Cancer (brca1, brca2)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Arm I

Participants receive oral tamoxifen once daily for 6 months in the absence of disease progression or unacceptable toxicity. After the completion of 6 months of treatment, participants are offered the opportunity to continue treatment for an additional 6 months.

Group Type: EXPERIMENTAL

tamoxifen citrate

Intervention Type: DRUG

Given orally

Arm II

Participants receive oral arzoxifene once daily for 6 months in the absence of disease progression or unacceptable toxicity. After the completion of 6 months of treatment, participants are offered the opportunity to continue treatment for an additional 6 months.

Group Type: EXPERIMENTAL

arzoxifene hydrochloride

Intervention Type: DRUG

Given orally

Arm III

Participants receive an oral placebo once daily once daily for 6 months in the absence of disease progression or unacceptable toxicity. After the completion of 6 months of treatment, participants are offered treatment with arzoxifene for an additional 6 months.

Group Type: PLACEBO_COMPARATOR

arzoxifene hydrochloride

Intervention Type: DRUG

Given orally

placebo

Intervention Type: OTHER

Given orally

Interventions

arzoxifene hydrochloride

Given orally

Intervention Type: DRUG

tamoxifen citrate

Given orally

Intervention Type: DRUG

placebo

Given orally

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• No ovarian cyst during screening
• No more than 12 months since prior Pap smear with normal cytological results OR human papilloma virus negative if atypical squamous cells of uncertain significance (ASCUS) present
• No higher degrees of atypia beyond ASCUS on Pap smear

• No known history of osteoporosis (bone mineral density > 1.5 standard deviations below young adult norms)
• Hormone receptor status
• Not specified

PATIENT CHARACTERISTICS:

Menopausal status

• Premenopausal, as defined by 1 of the following:

• Last menstrual period < 6 months ago
• Less than 45 years old AND underwent partial hysterectomy OR follicle-stimulating hormone within institutional pre-menopausal range within the past 3 months

Sex

• Female

Performance status

• ECOG 0-1

Life expectancy

• More than 2 years

Hematopoietic

• WBC ≥ 3,000/mm^3
• Platelet count ≥ 125,000/mm^3
• Hemoglobin ≥ 10 g/dL

Hepatic

• Bilirubin ≤ 1.5 mg/dL
• AST < 2 times upper limit of normal (ULN)
• Albumin ≥ 3.0 g/dL
• PT/PTT ≤ 1.25 times ULN

Renal

• Creatinine ≤ 1.5 mg/dL OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No history of deep venous thrombosis

Pulmonary

• No history of pulmonary embolism

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile participants must use effective barrier-method contraception during and for 3 months after completion of study treatment
• No other malignancy within the past 2 years except curatively treated basal cell or squamous cell skin cancer or cervical cancer ≤ stage I
• No known addiction
• Not undergoing treatment for an illicit drug addiction
• Willing and able to undergo required study procedures (e.g., research-related breast biopsies)

PRIOR CONCURRENT THERAPY:

Chemotherapy

• More than 2 years since prior chemotherapy

Endocrine Therapy

• At least 3 months since prior oral contraceptives or intramuscular progestational agent
• At least 3 months since prior luteinizing-hormone releasing hormone (LHRH) agonists or antagonists if agent was administered daily or monthly
• At least 6 months since prior LHRH agonists or antagonists if agent was administered every 3 months
• At least 6 months since prior antiestrogens (e.g., tamoxifen, toremifene, and raloxifene)
• No concurrent progestational or contraceptive agents

Radiotherapy

• See Disease Characteristics
• More than 2 years since prior radiotherapy

Surgery

• No prior prophylactic bilateral mastectomy

Other

• No concurrent cholestyramine
• No concurrent routine warfarin, bromocriptine, or phenobarbital
• No other concurrent investigational agents

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

The Cleveland Clinic

OTHER

Sponsor Role: lead

Responsible Party

Cleveland Clinic Foundation/Taussig Cancer Institute

Principal Investigators

George T. Budd, MD

Role: STUDY_CHAIR

The Cleveland Clinic

Other Identifiers

P30CA043703

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CASE-CCF-4713

Identifier Type: -

Identifier Source: org_study_id