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)