Official Title: “A Randomized Phase III Trial of Exemestane Versus Anastrozole in Postmenopausal Women With Receptor Positive Primary Breast Cancer”

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using exemestane or anastrozole may fight breast cancer by lowering the amount of estrogen the body makes. Giving exemestane or anastrozole after surgery may keep breast cancer from growing or coming back. It is not yet known whether exemestane is more effective than anastrozole in treating breast cancer.

PURPOSE: This randomized phase III trial is studying exemestane to see how well it works compared with anastrozole in treating postmenopausal women with hormone receptor-positive primary breast cancer.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label

Study Primary Completion Date: January 2011

OBJECTIVES:

Primary - Compare the event-free survival of postmenopausal women with hormone receptor-positive breast cancer treated with adjuvant exemestane vs anastrozole.

Secondary - Compare the overall survival of patients treated with these regimens. - Compare the time to distant recurrence in patients treated with these regimens. - Compare the incidence of new contralateral primary breast cancer in patients treated with these regimens. - Compare the incidence of all clinical fractures, specifically hip and vertebral fractures, in patients treated with these regimens. - Compare cardiovascular morbidity and mortality in patients treated with these regimens. - Compare the toxicities of these regimens in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to lymph node status (negative vs positive vs unknown), prior adjuvant chemotherapy (yes vs no), and trastuzumab (Herceptin^®) use (yes vs no). Patients are randomized to 1 of 2 treatment arms. - Arm I: Patients receive oral exemestane once daily. - Arm II: Patients receive oral anastrozole once daily. In both arms, treatment continues for 5 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed annually.

PROJECTED ACCRUAL: A total of 6,840 patients will be accrued for this study.

Intervention(s) in this Clinical Trial

• Drug: anastrozole
• Drug: exemestane
• Procedure: adjuvant therapy

Primary Measures

• Event-free survival
  • Safety Issue?: No

Secondary Measures

• Overall survival
  • Safety Issue?: No
• Time to distant recurrence
  • Safety Issue?: No
• Incidence of new contralateral primary breast cancer
  • Safety Issue?: No
• Long-term clinical and laboratory safety
  • Safety Issue?: Yes

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed invasive breast cancer meeting the following criteria:
• Complete resection of primary tumor
• Surgical margins must be clear of invasive carcinoma and ductal carcinoma in situ
• Stage I-III (T1-3, N0-3, M0) disease
• N3 allowed provided classification is solely based on presence of ≥ 10 involved axillary nodes
• Bilateral breast cancer allowed if cancers are synchronous (diagnosed at the same time)
• One or both tumors must have hormone receptor-positive markers
• No metachronous disease (diagnosed at different times)
• No locally recurrent or metastatic breast cancer
• Negative for metastases by the following radiologic methods:
• Bone scan
• Required only if alkaline phosphatase is ≥ 2 times upper limit of normal (ULN) and/or symptoms of metastatic disease
• Confirmatory x-ray or other imaging study (e.g., CT scan or MRI) required if bone scan results are questionable
• Abdominal ultrasound or CT scan of the abdomen
• Required only if AST/ALT or alkaline phosphatase ≥ 2 times ULN (except if the elevation is in the bone fraction)
• Chest x-ray
• No prior diagnosis of in situ carcinoma in the contralateral breast treated with partial mastectomy and/or hormonal therapy
• Prior or concurrent in situ carcinoma in the ipsilateral breast allowed if completely excised and patient did not receive hormonal therapy
• Hormone receptor status:
• Estrogen or progesterone receptor-positive disease

PATIENT CHARACTERISTICS:

• Female
• Postmenopausal, defined as one of the following:
• At least 60 years old
• Age 45-59 years with spontaneous cessation of menses for > 12 months prior to chemotherapy or study randomization
• Age 45-59 years with cessation of menses for < 12 months or secondary to hysterectomy AND a follicle-stimulating hormone (FSH) level in the postmenopausal range (or > 34.4 IU/L)
• Age 45-59 years on hormone replacement therapy (HRT) and discontinued HRT at diagnosis of breast cancer AND FSH level in the postmenopausal range (or > 34.4
• IU/L)
• Bilateral oophorectomy
• ECOG performance status 0-2
• Life expectancy ≥ 5 years
• WBC ≥ 3,000/mm³ OR granulocyte count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• AST and/or ALT < 2 times upper limit of normal*
• Alkaline phosphatase < 2 times ULN*
• No concurrent medical or psychiatric condition that would preclude study participation
• Able to swallow study medication and have adequate, unassisted oral intake to maintain a reasonable state of nutrition
• No history of other malignancies except adequately treated nonmelanoma skin cancer, curatively treated in situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years NOTE: *Unless imaging studies rule out metastases

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior aromatase inhibitor therapy
• No prior tamoxifen or selective estrogen-receptor modulators (SERMs) other than raloxifene
• At least 3 weeks since prior raloxifene
• At least 3 weeks but < 3 months since prior chemotherapy
• If no chemotherapy, > 3 weeks but < 3 months since prior primary surgery
• At least 3 weeks since prior and no concurrent hormones or steroids, including over-the-counter products and supplements considered to have an estrogenic effect including, but not limited to, any of the following:
• Ginseng
• EGb761 (ginkgo biloba)
• Black cohosh
• Angelica sinensis extract (dong quai)
• Fortified soy supplements/phytoestrogen preparations
• Prior and/or concurrent radiotherapy allowed
• Prior and/or concurrent trastuzumab (Herceptin^®) allowed
• Concurrent bisphosphonates allowed for prevention or treatment for osteoporosis but not as adjuvant therapy for breast cancer
• No concurrent estrogens, progesterones, or androgens
• Intermittent vaginal estrogens (e.g., estradiol, estrogen vaginal cream, or testosterone) for vaginal atrophy refractory to local measures allowed
• No concurrent SERMs
• No other concurrent endocrine therapy, hormonal therapy, steroids, or any other medication that would affect study endpoints

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 45 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Cancer Institute of Canada

Overall Clinical Trial Officials and Contacts

Paul E. Goss, MD, PhD Study Chair Massachusetts General Hospital  

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00438529

Study ID Number: CDR0000530110

ClinicalTrials.gov Identifier: NCT00438529

Health Authority: United States: Federal Government

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