Cabergoline in Metastatic Breast Cancer

PRIMARY OBJECTIVES:

I. To evaluate overall response rate (ORR) of cabergoline in women with metastatic breast cancer.

SECONDARY OBJECTIVES:

I. Evaluate the progression-free survival (PFS) and overall survival (OS). II. Evaluate toxicity. III. Correlate serum prolactin levels during therapy with response. IV. Evaluate within-patient changes in computed tomography (CT) and bone scan measurements taken at baseline and after 2 cycles of treatment.

V. Evaluate within-patient changes in prolactin receptor (PRLr) expression from baseline to after 1 cycle of treatment in those patients who consent to optional repeat biopsy.

OUTLINE:

Patients receive cabergoline orally (PO) twice weekly for weeks 1-4. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 6 months thereafter.

Inclusion criteria

• Patients must have histologically confirmed metastatic breast cancer; tissue (a minimum of 3 slides) from the most recent biopsy is required for review and confirmation of eligibility; NOTE: material should ideally be from the metastatic disease, however material from the primary tumor is acceptable if that is all that is available
• Patients must have stage IV breast cancer
• Patients must have tumors (primary or metastatic) that stain positively for the prolactin receptor
• Patients may have measurable or evaluable disease

• Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral CT scan
• Evaluable disease is disease that does not meet the criteria for measurable disease; examples would include patients with effusions or bone-only disease
• Women of childbearing potential must commit to the use of effective barrier (non-hormonal) contraception while on study
• Patients must have a life expectancy of greater than 12 weeks
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Patients may have had a prior diagnosis of cancer if it has been > 5 years since their last treatment
• Leukocytes >= 3,000/uL (microliter)
• Absolute neutrophil count >= 1,500/uL
• Platelets >= 100,000/uL
• Child Pugh score =< 10
• Patients must be able to swallow and retain oral medication
• All patients must have given signed, informed consent prior to registration on study

Exclusion criteria

• Women who are pregnant or lactating are not eligible for study treatment
• Patients who are undergoing concomitant radiotherapy are NOT eligible for participation
• Patients who are receiving any other investigational agents or concurrent anticancer therapy are NOT eligible for participation; previous systemic treatment is allowed with a 2 week washout period prior to registration
• Patients who are taking any herbal (alternative) medicines are NOT eligible for participation; patients must be off any such medications by the time of registration
• Patients who are receiving concomitant D2-antagonists (such as phenothiazines, butyrophenones, thioxanthenes, or metoclopramide) are NOT eligible for participation; patients must be off any such medications by the time of registration
• Patients with known brain metastases are NOT eligible for participation
• Patients with any of the following conditions or complications are NOT eligible for participation:

• Uncontrolled hypertension
• Known hypersensitivity to ergot derivatives
• History of cardiac valvular disorders, as suggested by anatomical evidence of valvulopathy of any valve (to be determined by pre-treatment evaluation including echocardiographic demonstration of valve leaflet thickening, valve restriction, or mixed valve restriction-stenosis)
• History of pulmonary, pericardial, cardiac valvular, or retroperitoneal fibrotic disorders
• Gastrointestinal (GI) tract disease resulting in an inability to take oral medication
• Malabsorption syndrome
• Require intravenous (IV) alimentation
• History of prior surgical procedures affecting absorption
• Uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis)