Phase III Study of Atamestane Plus Toremifene Versus Letrozole in Advanced Breast Cancer

Inclusion Criteria:

Women age 18 years or older
Pathological or histological confirmation of breast cancer at initial diagnosis or at the time of metastases
ECOG performance status of 0, 1 or 2 or Karnofsky performance status of 60 or higher
Predicted life expectancy of 12 weeks or more
Postmenopausal endocrine status. LH/FSH levels in the postmenopausal range in women whose menopause occurred less than 5 years ago
Locally recurrent, locally advanced, locally metastatic disease not amenable to radiation therapy or surgery and/or distant metastatic disease
At least one tumor localization measurable in 2 dimensions (one diameter at least 2 cm for soft tissue/visceral disease assessed by CT/MRI scan or conventional X-ray technique, one diameter at least 1 cm for bone lesions assessed by conventional X-ray techniques)
Estrogen receptor and/or progesterone receptor positive (by laboratory/institutional standard) at the time of initial diagnosis or determined during subsequent biopsy/surgery of metastases
Written informed consent obtained

Exclusion Criteria:

Prior hormonal therapy to treat locally recurrent, locally advanced or metastatic disease
Prior adjuvant therapy with aromatase inhibitors or antiestrogens/SERMs within 12 months prior to enrollment
Progression of disease during therapy with antiestrogens (including SERMs administered for prevention of osteoporosis)
Life-threatening locally recurrent, locally advanced or metastatic disease or disease requiring chemotherapeutic intervention (such as inflammatory breast cancer)
History of known CNS metastases, significant neurological dysfunction including active seizures, or clinical signs of other significant neurological diseases
Other active malignancy (except basal cell carcinoma of the skin or in situ cervical cancer). Patients with previous malignancies must be without evidence of disease for at least five years
Renal insufficiency (serum creatinine > 2.0 mg/dL)
Aspartate aminotransferase, alanine aminotransferase or serum bilirubin levels more than 2.5 times upper limit of normal
Hemoglobin <9 g/dL
Platelet count of less than 100,000 platelets per mm3
Total white blood cell count of less than 2,000 cells per mm3
Premenopausal endocrine status; pregnant or lactating females
Usage of an investigational drug within the thirty (30) days prior to enrollment; or the planned usage of an investigational drug other than the study medication during the course of the current study
Contraindication to use of toremifene, atamestane, letrozole or any of the inactive components of their formulations
Prior enrollment in this study