Recurrent Breast Cancer, Stage IV Breast Cancer
Conditions
Brief summary
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
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.
Interventions
Given IV
Correlative studies
Sponsors
Study design
Eligibility
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective tumor response (CR + PR) | Up to 24 months | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to progression | Up to 3 years | Will be reported using the Kaplan-Meier method with 95% confidence intervals indicated. |
| Overall survival | Up to 3 years | Will be reported using the Kaplan-Meier method with 95% confidence intervals indicated. |
| Correlation between variations in the serum levels of adhesion molecules and angiogenic factors | Up to 24 months | Will be evaluated and descriptive analysis will be performed. |
| Tissue markers of biological activity | Up to 24 months | 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. |
Countries
United States