Cabergoline in Metastatic Breast Cancer

Study Overview
=================
Brief Summary
-----------------
Prolactin is a hormone produced in the pituitary gland. Previous studies have revealed that elevated levels of the hormone prolactin might be associated with an increased risk of breast cancer. Cabergoline has been shown to lower prolactin levels in the blood. The purpose of this study is to evaluate the effectiveness of cabergoline in treating metastatic breast cancer disease in those who test positive for the prolactin receptor.

Detailed Description
-----------------
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.

Official Title
-----------------
A Pilot Phase II Trial of Cabergoline in the Treatment of Metastatic Breast Cancer

Conditions
-----------------
Recurrent Breast Cancer, Stage IV Breast Cancer

Intervention / Treatment
-----------------
* Drug: cabergoline


Participation Criteria
=================
Eligibility Criteria
-----------------
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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (cabergoline)<br>Patients receive cabergoline oral (PO) twice weekly for weeks 1-4. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. | Drug: cabergoline<br>* Given orally<br>* Other names: FCE 21336;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) at 2 Months | Overall Response Rate (ORR) is defined as the number of patients that achieved Complete Response (CR) or Partial Response (PR) and will be assessed after 8 weeks (2 cycles) of therapy using CT scan images and RECIST guidelines. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of LD. Progressive Disease (PD): At least a 20% increase in the sum o the LD of target lesions, taking as reference the smallest sum of LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of LD since the treatment started | After 8 weeks (2 cycles) of treament | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | Progression Free Survival (PFS) will be measured from time of treatment initiation until first documentation of progression of disease or death from any cause. | From start of treatment until progression of disease or death | 
| Treatment Toxicity | Toxicity will be assessed at the beginning of each cycle (1 cycle equals 28 days) during treatment and 30 days post last treatment during treatment. Toxicity will be assessed according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0). In general adverse events (AEs) will be graded according to the following: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE Grades 1 through 4 adverse events that were determined to be at least possibly related to treatment are combined and reported below. | After every 4 weeks (1 cycle) during treatment for up to 20 cycles and 30 days post last treatment | 
| Change in Within-patient Imaging Measurements at Baseline and After 2 Cycles | At baseline and after 2 cycles changes CT and bone scan measurements will be evaluated. | At baseline and at 8 weeks | 
| Change in Prolactin Receptor Expression Measurements at Baseline and After 1 Cycle | Evaluate prolactin expression in biopsy tissue taken at baseline and after 4 weeks (1 cycle) of treatment. | At baseline and after 4 weeks (1 cycle) | 
| Correlate Tissue Prolactin Biomarkers With Response to Therapy | Baseline tumor tissue was analyzed for prolactin receptor (PRLr) expression and was provided with an IHC-based Allred score of 0 to 300 based on percentage intensity where lower scores indicate less PRLr expression and high scores indicate more PRLr expression. Only the malignant epithelium was scored. The score was correlated with best response of patient. | At baseline | 
| Overall Survival (OS) | Overall Survival (OS) is defined from the first day of treatment until death from any cause. | From the start of treatment until death from any cause. Median follow up time of 6.817 months (95%CI 0.22-26.18) |