A Phase II, Randomized, Open-Label Study Of Letrozole In Combination With Two Dose Levels And Schedules Of Oral CCI-779, Or Letrozole Alone, In Postmenopausal Women With Locally Advanced Or Metastatic Breast Cancer

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed breast cancer

- Locally advanced disease

- Not amenable to curative surgery and/or radiotherapy OR

- Metastatic disease

- Stage IIIB, IIIC, or IV

- Measurable disease

- Presenting with de novo advanced or metastatic cancer OR tumor progression in 1 of
the following ways:

- During or after completing adjuvant tamoxifen therapy

- During first-line metastatic therapy with tamoxifen

- Disease limited to the bone allowed provided at least 2 bone metastases exist
(including at least 1 osteolytic lesion), each having a unilateral dimension of at
least 1 cm

- No CNS metastases

- No hepatic metastases that constitute extensive visceral disease or are acutely life
threatening

- No symptomatic pulmonary lymphangitic metastases

- No prior inflammatory breast cancer

- Must be appropriate to receive endocrine therapy as treatment for advanced disease

- Hormone receptor status:

- Estrogen and/or progesterone receptor positive

PATIENT CHARACTERISTICS:

Age

- 18 and over

Sex

- Female

Menopausal status

- Postmenopausal defined by 1 of the following:

- Radiation-induced menopause or surgical bilateral oophorectomy

- Intact uterus and any of the following:

- Older than 55 years of age

- No menses for the past 5 years

- 55 years of age or younger and no menses for at least the past 12 months
(but has had menses in the past 5 years) and postmenopausal levels of
follicle-stimulating hormone (FSH) (i.e., concentration greater than the
lower limit of normal)

- No intact uterus and either of the following:

- Older than 55 years of age

- 55 years of age or younger and has FSH levels in the postmenopausal range

Performance status

- ECOG 0-2

Life expectancy

- At least 6 months

Hematopoietic

- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- Hemoglobin at least 8.5 g/dL

Hepatic

- Bilirubin no greater than 1.5 times upper limit of normal (ULN)

- AST and ALT no greater than 3 times ULN (5 times ULN if liver metastases are present)

- Hepatitis B surface antigen negative

- Hepatitis C virus negative

Renal

- Creatinine no greater than 1.5 times ULN

- Calcium no greater than 11 mg/dL (2.75 mmol/L)

Cardiovascular

- No myocardial infarction within the past 6 months

- No unstable angina

- No known pulmonary hypertension

Other

- Not pregnant

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 12 weeks after study
participation

- Cholesterol no greater than 350 mg/dL (9.0 mmol/L)

- Triglycerides no greater than 400 mg/dL (4.56 mmol/L)

- Able to swallow whole tablets

- HIV negative

- Not immunocompromised

- No other malignancy within the past 5 years except appropriately treated carcinoma in
situ of the cervix, basal cell or squamous cell skin cancer, or contralateral breast
cancer

- No other serious concurrent illness

- No known hypersensitivity to any of the components in letrozole or CCI-779

- No other major illness that would increase the risk associated with study
participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

- At least 6 months since prior trastuzumab (Herceptin)

- At least 3 weeks since prior biologic therapy

- At least 3 weeks since prior immunologic therapy

- No concurrent immunotherapy

- No concurrent prophylactic use of growth factors except erythropoietic agents

Chemotherapy

- At least 6 months since prior adjuvant chemotherapy

- No prior chemotherapy for locally advanced disease or in the metastatic setting

- No concurrent cytotoxic chemotherapy

- No prior CCI-779

Endocrine therapy

- See Disease Characteristics

- At least 3 weeks since prior hormonal therapy (adjuvant or metastatic setting)

- Prior adjuvant antiestrogens allowed

- No prior aromatase inhibitors

- No other concurrent aromatase inhibitors

- No concurrent hormonal agents

- Concurrent corticosteroids for physiologic replacement allowed

Radiotherapy

- See Disease Characteristics

- At least 3 weeks since prior local radiotherapy

- No prior radiotherapy to more than 25% of the marrow

- Concurrent radiotherapy allowed with the following criteria:

- Palliative radiotherapy allowed for pain control or other reasons with no
curative intent

- Tumor progression should be ruled out before therapy

- No radiotherapy to more than 25% of the bone marrow

- No radiotherapy including all of the target lesions

Surgery

- At least 3 weeks since prior surgery

Other

- At least 3 weeks since prior immunosuppressive agents

- No ongoing maintenance therapy for life-threatening ventricular arrhythmia

- No other concurrent anticancer therapy

- No other concurrent investigational therapy

- No concurrent immunosuppressive therapy

- No concurrent ketoconazole

- No concurrent phenobarbitol, carbamazepine, or phenytoin

- No concurrent Hypericum perforatum (St. John's wort)