PS-341 in Treating Women With Metastatic Breast Cancer

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.

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