PS-341 in Treating Women With Metastatic Breast Cancer

Study Overview
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Brief Summary
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PS-341 may stop the growth of tumor cells by blocking the enzymes necessary for cancer cell growth. Phase II trial to study the effectiveness of PS-341 in treating women who have metastatic breast cancer

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the efficacy of PS-341, in terms of response rate, in women with metastatic breast cancer. SECONDARY OBJECTIVES: I. Determine the clinical activity of this drug, in terms of progression-free survival, in these women. II. Determine the toxicity profile and tolerability of this drug in these women. III. Determine the pharmacodynamics of this drug in these women. OUTLINE: Patients receive PS-341 IV over 3-5 seconds twice weekly on weeks 1 and 2. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. PROJECTED ACCRUAL: A maximum of 12-35 patients will be accrued for this study within 9-12 months.

Official Title
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Phase II Trial Of PS-341 In Metastatic Breast Cancer

Conditions
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Recurrent Breast Cancer, Stage IV Breast Cancer

Intervention / Treatment
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* Drug: bortezomib
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed invasive breast cancer Clinical and/or radiological evidence of stage IV disease Relapsed or resistant disease within 6-12 months after completion of prior chemotherapy with doxorubicin or epirubicin and/or paclitaxel or docetaxel foradvanced disease or in the adjuvant setting At least 1 unidimensionally measurable lesion At least 20 mm by conventional techniques At least 10 mm by spiral CT scan No bone metastases as only measurable site Pleural or peritoneal effusions not acceptable as measurable disease No known brain metastases Hormone receptor status: Estrogen receptor-negative Estrogen receptor-positive Female Performance status - ECOG 0-2 Performance status - Karnofsky 60-100% More than 12 weeks WBC at least 3,000/mm^3 Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Bilirubin normal AST or ALT no greater than 2.5 times upper limit of normal Creatinine normal Creatinine clearance at least 60 mL/min No acute ischemia or significant conduction abnormality by EKG No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia LVEF greater than 50% No uncontrolled concurrent illness No psychiatric illness or social situation that would preclude study No ongoing or active infection No prior allergic reaction(s) to compounds of similar chemical or biologic composition to PS-341 No other malignancy within the past 5 years except carcinoma in situ of the cervix or basal cell skin cancer Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier-method contraception See Chemotherapy See Disease Characteristics No more than 1 prior chemotherapy regimen for metastatic disease High-dose regimen or bone marrow transplantation considered 1 prior regimen At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered Prior hormonal therapy for metastatic disease or in adjuvant setting allowed Prior localized radiotherapy allowed if it does not influence the signal evaluable lesion At least 4 weeks since prior radiotherapy and recovered At least 2 weeks since prior minor surgery and recovered At least 4 weeks since prior major surgery and recovered No other concurrent investigational agent No other concurrent investigational or commercial agents or therapies to treat this malignancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (bortezomib)<br>Patients receive PS-341 IV over 3-5 seconds twice weekly on weeks 1 and 2. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. | Drug: bortezomib<br>* Given IV<br>* Other names: VELCADE;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective tumor response (CR + PR) | The agent would be of definite interest for further investigation if the associated response rate is at least 30% (p1), and would not be of further interest if the response rate is below 10% (p0). | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression | Will be reported using the Kaplan-Meier method with 95% confidence intervals indicated. | Up to 3 years | 
| Overall survival | Will be reported using the Kaplan-Meier method with 95% confidence intervals indicated. | Up to 3 years | 
| Correlation between variations in the serum levels of adhesion molecules and angiogenic factors | Will be evaluated and descriptive analysis will be performed. | Up to 24 months | 
| Tissue markers of biological activity | Will be described in case of lesions amenable to tissue biopsy. The plasma pharmacodynamics of PS-341 as measured by the 20S-proteosome assay, will be used to measured the biological activity of the drug and correlated with response to treatment and variations in biomarkers. | Up to 24 months |