Exemestane in Preventing Cancer in Postmenopausal Women at Increased Risk of Developing Breast Cancer - Full Text View

Sponsor:	NCIC Clinical Trials Group
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00083174

Purpose

RATIONALE: Hormone therapy using exemestane may fight breast cancer by reducing the production of estrogen and progesterone.

PURPOSE: This randomized phase III trial is studying exemestane to see how well it works in preventing cancer in postmenopausal women who are at increased risk of developing breast cancer.

Condition	Intervention	Phase
Breast Cancer	Drug: exemestane Other: placebo	Phase III

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double-Blind, Placebo Control
Official Title:	A Phase III Randomized Study of Exemestane Versus Placebo in Postmenopausal Women at Increased Risk of Developing Breast Cancer

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Exemestane

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Invasive breast cancer-free survival after 38 events (about 4 years after start of study) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Invasive and noninvasive breast cancer-free survival at about 4 years after start of study [ Designated as safety issue: No ]
Clinical fracture rate at about 4 years after start of study [ Designated as safety issue: No ]
Cardiac events at about 4 years after start of study [ Designated as safety issue: No ]
Menopausal symptoms as assessed by MENQOL questionnaire at about 4 years after start of study [ Designated as safety issue: No ]
Quality of Life assessed by SF36 at about 4 years after start of study [ Designated as safety issue: No ]

Estimated Enrollment:	4560
Study Start Date:	February 2004
Estimated Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Experimental Patients receive oral exemestane once daily for 5 years.	Drug: exemestane Given orally
Arm II: Placebo Comparator Patients receive oral placebo once daily for 5 years.	Other: placebo Given orally

Detailed Description:

OBJECTIVES:

Primary

Compare the incidence of invasive breast cancer in postmenopausal women at increased risk of developing breast cancer when treated with exemestane vs placebo.

Secondary

Compare reduction in total incidence of invasive and non-invasive (ductal carcinoma in situ) breast cancer in patients treated with these regimens.
Compare reduction in total incidence of receptor-negative invasive breast cancer in patients treated with exemestane vs placebo.
Compare the incidence of lobular cancer in situ and atypical ductal hyperplasia in patients treated with these regimens.
Compare the number of clinical breast biopsies in patients treated with these regimens.
Compare the incidence of all clinical fractures, and specifically hip and vertebral fractures, in patients treated with these regimens.
Compare the incidence of clinically relevant cardiac events (i.e., significant coronary heart disease) in patients treated with these regimens.
Compare the impact of these regimens on menopausal symptoms and quality of life of these patients.
Compare adverse effects of these regimens in these patients.
Compare the incidence of other malignancies in patients treated with these regimens.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to concurrent low dose (≤ 100 mg/day) aspirin use (yes vs no) and Gail score (≤ 2 vs > 2). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive oral exemestane once daily for 5 years.
Arm II: Patients receive oral placebo once daily for 5 years. In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, every 6 months for 1 year, and then annually for 4 years.

Patients are followed every 6 months for 1 year and then annually thereafter.

PROJECTED ACCRUAL: A total of 4,560 patients (2,280 per treatment arm) will be accrued for this study within 3 years.

Eligibility

Ages Eligible for Study:	35 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

DISEASE CHARACTERISTICS:

At increased risk of developing breast cancer, due to at least one of the following risk factors:
- Gail score > 1.66
- Age ≥ 60 years
- Prior atypical ductal hyperplasia or lobular carcinoma in situ on breast biopsy
- Prior ductal carcinoma in situ (DCIS) treated with mastectomy
  - No prior DCIS treated with adjuvant tamoxifen
No prior invasive breast cancer
Hormone receptor status:
- Not specified

PATIENT CHARACTERISTICS:

Age

35 and over

Sex

Female

Menopausal status

Postmenopausal, defined as one of the following:
- > 50 years of age with no spontaneous menses for at least 12 months before study entry
- ≤ 50 years of age with no menses (spontaneous or secondary to hysterectomy) for at least 12 months before study entry AND with follicle-stimulating hormone level within postmenopausal range
- Bilateral oophorectomy

Performance status

Not specified

Life expectancy

Not specified

Hematopoietic

Not specified

Hepatic

Not specified

Renal

Not specified

Other

No other malignancies within the past 5 years except adequately treated nonmelanoma skin cancer, curatively treated carcinoma in situ of the cervix, or other curatively treated solid tumors with no evidence of disease for ≥ 5 years
No uncontrolled hypothyroidism or hyperthyroidism
No major medical or psychiatric illness (including substance and alcohol abuse within the past 2 years) that would preclude study participation or compliance
Willing to complete quality of life questionnaires in either English or French

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

Not specified

Endocrine therapy

See Disease Characteristics
More than 3 months since prior and no concurrent hormone replacement therapies
More than 3 months since systemic estrogenic, androgenic, or progestational agents
More than 3 months since prior and no concurrent hormonal therapies, including, but not limited to the following:
- Luteinizing-hormone releasing-hormone analogs (e.g., goserelin or leuprolide)
- Progestogens (e.g., megestrol)
- Prolactin inhibitors (e.g., bromocriptine)
- Antiandrogens (e.g., cyproterone acetate)
- Selective estrogen-receptor modulators (e.g., tamoxifen, toremifene, or raloxifene)
No concurrent endocrine therapy
No concurrent estrogens, androgens, or progesterones

Radiotherapy

Not specified

Surgery

See Disease Characteristics
See Menopausal status

Other

More than 30 days or 5 half-lives since prior investigational drugs
Concurrent low dose (≤ 100 mg/day) prophylactic aspirin allowed
Concurrent bisphosphonates for prevention or treatment of osteoporosis allowed
No other concurrent medications that may have an effect on study endpoints

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00083174

Show 66 Study Locations

Sponsors and Collaborators

NCIC Clinical Trials Group

Investigators

Study Chair:

Paul E. Goss, MD, PhD

Massachusetts General Hospital

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Web site for additional information This link exits the ClinicalTrials.gov site

Publications:

Goss PE, Richardson H, Chlebowski R, Johnston D, Sarto GE, Maunsell E, Ingle JN, Alés-Martinez JE. National Cancer Institute of Canada Clinical Trials Group MAP.3 Trial: evaluation of exemestane to prevent breast cancer in postmenopausal women. Clin Breast Cancer. 2007 Dec;7(11):895-900. No abstract available.

Moy B, Richardson H, Johnston D, et al.: NCIC CTG MAP.3: enrollment and study drug adherence of ethnic minority women in a breast cancer prevention trial. [Abstract] Breast Cancer Res Treat 106 (1): A-3048, S141-2, 2007.

Richardson H, Johnston D, Goss PE, et al.: Participant characteristics on an international NCIC CTG breast cancer prevention trial. [Abstract] J Clin Oncol 25 (Suppl 18): A-1531, 2007.

Richardson H, Johnston D, Pater J, Goss P. The National Cancer Institute of Canada Clinical Trials Group MAP.3 trial: an international breast cancer prevention trial. Curr Oncol. 2007 Jun;14(3):89-96.

Responsible Party:	Cancer Research Institute at Queen's University ( Joseph L. Pater )
Study ID Numbers:	CDR0000363802, CAN-NCIC-MAP3, PFIZER-EXEAPO-0028-150, ExCel
Study First Received:	May 14, 2004
Last Updated:	December 23, 2009
ClinicalTrials.gov Identifier:	NCT00083174 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

breast cancer

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site
Molecular Mechanisms of Pharmacological Action
Skin Diseases
Antineoplastic Agents
Therapeutic Uses

Breast Neoplasms
Enzyme Inhibitors
Exemestane
Aromatase Inhibitors
Pharmacologic Actions
Breast Diseases

ClinicalTrials.gov processed this record on February 08, 2010