Official Title: “Combined Estrogen Blockade of the Breast With Exemestane and Raloxifene in Estrogen Receptor (ER)-Negative and Progesterone Receptor (PR)-Negative Postmenopausal Women With a History of Breast Cancer Who Have No Clinical Evidence of Disease”

RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using exemestane may fight breast cancer by blocking the use of estrogen by the tumor cells.

Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. Raloxifene may be effective in preventing the recurrence of breast cancer.

PURPOSE: Randomized phase II trial to evaluate the effectiveness of exemestane and raloxifene in treating postmenopausal women who have a history of ductal carcinoma in situ, stage I, stage II, or stage III breast cancer.

Study Type: Interventional

Study Design: Prevention, Randomized, Active Control

OBJECTIVES: - Evaluate the clinical safety and toxicity of raloxifene in combination with exemestane in postmenopausal women with a history of stage 0 (ductal carcinoma in situ), I, II, or III breast cancer who have no clinical evidence of disease after completion of all planned adjuvant therapy. - Evaluate the effects of this combination on plasma concentrations of estrogens, markers of bone turnover and bone mineral density, serum lipoprotein profile, and quality of life in this patient population. - Determine the pharmacokinetics and the pharmacodynamics of this combination in these patients. - Determine the feasibility of using mammography and breast MRI to assess the effects of this drug combination on radiographic breast density.

OUTLINE: This is a randomized study. Patients are randomized to one of two treatment arms. - Arm I: Patients receive oral raloxifene once a day for 2 weeks. - Arm II: Patients receive oral exemestane once a day for 2 weeks. After 2 weeks of single agent therapy, all patients receive combination therapy with oral raloxifene and oral exemestane once a day for 1 year in the absence of unacceptable toxicity or disease recurrence. At the end of 1 year, patients may continue receiving raloxifene alone or raloxifene plus exemestane for a maximum duration of 5 years.

Quality of life is assessed at baseline, and then at 3, 6, and 12 months. Patients who continue treatment after 1 year have quality of life assessed at 24, 36, 48, and 60 months.

Patients are followed every 3 months for the first year. Patients who continue treatment after 1 year are followed every 6 months through the fifth year.

PROJECTED ACCRUAL: A total of 30 patients (15 per arm) will be accrued for this study.

Intervention(s) in this Clinical Trial

• Drug: exemestane
• Drug: raloxifene
• Procedure: adjuvant therapy

DISEASE CHARACTERISTICS:

• Stage 0 (ductal carcinoma in situ), I, II, or III breast cancer with no clinical evidence of disease after completion of all planned adjuvant therapy
• No prior antiestrogen therapy as adjuvant therapy
• Histologically confirmed history of breast cancer
• CEA and CA15-3 normal
• No prior bilateral mastectomy
• Hormone receptor status:
• Progesterone and estrogen receptor negative OR
• Progesterone and/or estrogen receptor positive

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Menopausal status:

• Postmenopausal, as defined by 1 of the following:
• No spontaneous menses for at least 5 years
• If prior hysterectomy, but have intact ovaries, must have luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels within postmenopausal range
• Spontaneous menses within the past 5 years, but amenorrheic (e.g., spontaneous or secondary to chemotherapy, radiotherapy, or hysterectomy) for at least 12 months, and LH and FSH levels within postmenopausal range
• Bilateral oophorectomy

Sex:

• Female

Performance status:

• Karnofsky 80-100%

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• AST no greater than 2 times upper limit of normal

Renal:

• Creatinine no greater than 1.5 mg/dL

Cardiovascular:

• No unstable angina
• No New York Heart Association class III or IV heart disease
• No history of venous thrombosis

Pulmonary:

• No history of pulmonary embolism

Other:

• No prior ovarian or endometrial cancer
• No prior or concurrent osteoporosis, as defined by lumbar spine bone mineral density less than 2.5 SD below the mean value for normal premenopausal women

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 4 weeks since prior chemotherapy for breast cancer

Endocrine therapy:

• See Disease Characteristics
• At least 3 months since prior hormonal therapy
• At least 3 months since prior calcitonin
• No adjuvant tamoxifen

Radiotherapy:

• At least 4 weeks since prior radiotherapy for breast cancer

Surgery:

• See Disease Characteristics
• At least 4 weeks since prior surgery for breast cancer
• More than 2 years since prior initial surgery

Other:

• At least 3 months since prior bisphosphonates

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Memorial Sloan-Kettering Cancer Center

Overall Clinical Trial Officials and Contacts

Maura N. Dickler, MD Study Chair Memorial Sloan-Kettering Cancer Center  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00004247

Study ID Number: CDR0000067493

ClinicalTrials.gov Identifier: NCT00004247

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database