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)