Intermittent Letrozole Therapy in Postmenopausal Women With Metastatic Breast Cancer

A Phase II Clinical Trial of Intermittent Letrozole Therapy in Postmenopausal Women With CA 15-3 Positive (Carcinoma Antigen 15-3), Hormone Receptor Positive, Metastatic Breast Cancer

The purpose of this research study is to study the effects of using aromatase inhibitor (AI) therapy intermittently on participants with breast cancer. AIs are a class of drugs used to treat breast cancer in postmenopausal women. They work by decreasing the level of estrogen, which is believed to stimulate the growth of tumor tissue. Breast cancer that progresses despite therapy with an AI is thought to have become resistant to AI therapy. There is scientific evidence to suggest that resistant breast cancer cells learn to grow at the very low levels of estrogen present on AI therapy, and that increasing estrogen levels even slightly by stopping AI therapy may inhibit the breast cancer cells.

• This study involves treating participants with intermittent AI therapy. The AI will be stopped at the time they enter the study. We plan on monitoring a marker in the participants blood called CA 15-3 (or CA 27.29) every 4 weeks to help us make a decision of when to re-start treatment with letrozole (femara). This marker is known to rise when disease is progressing and drop when the disease is responding to treatment. We will be stopping and re-starting therapy based on the changes of CA 15-3 in the participants blood.
• In addition to bloodwork, the following tests and procedures will be performed on a monthly basis: medical history; physical examination and performance status.
• Every 8 weeks the following will be performed: Tumor assessment by physical exam (if possible); Chest x-ray or CT scan or chest; CT scans of abdomen and pelvis; and bone scan.

Inclusion Criteria:

• Female
• 18 years of age or older
• Postmenopausal
• Histologically or cytologically confirmed adenocarcinoma of the breast with locally advanced or metastatic disease this is not considered amenable to curative treatment with elevation of CA 15-3 documented at the time of diagnosis of metastatic disease and prior to initiation of letrozole or anastrozole therapy
• Current letrozole or anastrozole monotherapy with a documented CA 15-3 level that has decreased by at least 50% of the patients baseline
• Letrozole or anastrozole must be discontinued at the time of study enrollment
• Evidence of hormone sensitivity of primary or secondary tissue.
• Measurable or nonmeasurable (but evaluable-defined as nontarget lesions) disease according to modified RECIST
• Prior antiestrogen therapies including tamoxifen, steroidal AIs, nonsteroidal AIs, or fulvestrant in the adjuvant setting is allowed provided the patient is currently on letrozole or anastrozole monotherapy as first-line therapy for metastatic disease
• Life expectancy of greater than 3 months
• ECOG (Eastern Cooperative Oncology Group) Performance Status of 0,1, or 2
• Normal organ and marrow function as outlined in protocol

Exclusion Criteria:

• Premenopausal
• Trastuzumab or biologic therapy within 2 weeks
• Prior or planned radiation therapy to a site of evaluable disease in the event that the site is the only site of evaluable disease
• Concomitant anticancer treatments including trastuzumab, chemotherapy, or other biologic agents other than letrozole or anastrozole therapy
• Chronic bisphosphonates for hypercalcemia or prevention of bone metastases.
• Treatment with non-approved or investigational agent within 2 weeks before study entry
• Presence of life-threatening metastatic disease, defined as extensive hepatic involvement, or past or present brain or leptomeningeal involvement, or symptomatic pulmonary lymphangitic spread
• Patients who are highly symptomatic from their breast cancer, or who require urgent palliative chemotherapy, as decided by their treating physician
• Previous or current systemic malignancy within the past five years, except for contralateral breast carcinoma, in situ carcinoma of the cervix treated by cone biopsy, or adequately treated basal or squamous cell carcinoma of the skin.
• Any severe concomitant condition believed to render subject undesirable for participation