Phase II Trial of Bortezomib and Doxorubicin in Metastatic Breast Cancer

Study Overview
=================
Brief Summary
-----------------
Primary objective is to determine the effectiveness of the combination of bortezomib and doxorubicin in patients with metastatic breast cancer. The trial format is a single arm Phase II design wherein patients are treated with bortezomib IV on days 1, 4, 8, and 11 and with doxorubicin IV on days 1 and 8 of a 21-day cycle.

Official Title
-----------------
A Phase II Trial of Bortezomib and Doxorubicin in Metastatic Breast Cancer

Conditions
-----------------
Metastatic Breast Cancer

Intervention / Treatment
-----------------
* Drug: PS-341, doxorubicin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Cytologically or histologically confirmed metastatic breast cancer Measurable or evaluable disease Age > 18, PS 0,1,2 MUGA > 45% Received one or fewer chemotherapies or investigational regimens for metastatic disease, no limit to the number of prior hormonal therapies. May have had single agent Herceptin and/or Herceptin plus single-agent chemotx. Must meet designated laboratory criteria within 14 days of enrollment Exclusion Criteria: Doxorubicin for metatstatic disease. Pregnant or lactating. Active infections, no myocardial infarction within 2 months of enrollment. Investigational drugs within 14 days of enrollment. Chemotherapy, radiotherapy, hormonal therapy or other investigational therapy within 4 weeks of enrollment. Neuropathy that is > grade 2. Active brain mets. Hypersensitivity to bortezomib, boron, or mannitol.

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: A<br> | Drug: PS-341, doxorubicin<br>* bortezomib:1.3 mg/m2 IVP over 3-5 sec. days 1, 4, 8, 11 of 21 day cycle doxorubicin: 20 mg/m2 IV over 3-5 min. days 1,8 (one hour after bortezomib) of 21 day cycle<br>* Other names: Adriamycin;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Determine the clinical efficacy of bortezomib and doxorubicin in patients with metastatic breast cancer. Overall response rate is defined as both complete and partial response per RECIST, where complete response is the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10mm. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. | Every two cycles/42 days, up to 7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression | Number of days to progression, where progression is defined as the number of days from the day of first study drug administration to the day the patient experiences an event of disease progression, or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. If a patient has not experienced an event of disease progression, then the patient's data will be censored at the date of the last available evaluation. Progression-free survival will be summarized by medium time to progression. | Up to one year |