Breast Cancer
Conditions
Keywords
male breast cancer, recurrent breast cancer, stage IV breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer
Brief summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of perifosine in treating patients who have recurrent, refractory, locally advanced, or metastatic breast cancer.
Detailed description
OBJECTIVES: * Determine the objective tumor response rate in patients with recurrent or refractory, locally advanced or metastatic breast cancer treated with perifosine. * Determine the toxicity of this drug in these patients. * Determine the stable disease rate, time to disease progression, objective response duration, and duration of stable disease in patients treated with this drug. * Correlate potential endpoints, including phosphorylated ERK, PKB, and SAPK, phosphorylated PKC alpha, beta, and gamma isoforms, p21 \^WAF1; and activated capase-3 in tumor biopsies, with clinical outcome in patients treated with this drug. OUTLINE: This is an open-label, multicenter study. Patients receive a loading dose of oral perifosine on days 1 and 2 and once daily on days 3-21 during course 1. Patients receive oral perifosine once daily on days 1-21 in each subsequent course. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) may receive 2 additional courses beyond the CR. PROJECTED ACCRUAL: A total of 18-35 patients will be accrued for this study within 6-12 months.
Interventions
DRUGperifosine
Sponsors
National Cancer Institute (NCI)
University Health Network, Toronto
Study design
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed breast cancer * Recurrent or refractory, locally advanced or metastatic disease * At least 1 unidimensionally measurable lesion * At least 20 mm by conventional techniques OR 10 mm by spiral CT scan * Previously irradiated lesions are not considered measurable unless they have demonstrated progression before study entry * No measurable disease limited to bone lesions * No known brain metastases * Hormone receptor status: * Not specified PATIENT CHARACTERISTICS: Age * 18 and over Sex * Male or female Menopausal status * Not specified Performance status * ECOG 0-2 OR * Karnofsky 60-100% Life expectancy * More than 3 months Hematopoietic * WBC at least 3,000/mm\^3 * Absolute neutrophil count at least 1,500/mm\^3 * Platelet count at least 100,000/mm\^3 * No history of hemolytic disorder Hepatic * Bilirubin no greater than 1.25 times upper limit of normal (ULN) * AST/ALT no greater than 2.5 times ULN (5 times ULN if liver metastases present) Renal * Creatinine normal OR * Creatinine clearance at least 60 mL/min Cardiovascular * No symptomatic congestive heart failure * No unstable angina pectoris * No cardiac arrhythmia * No evidence of cardiac dysfunction Gastrointestinal * No history of biliary flow obstruction * No abnormalities of the gastrointestinal tract that would preclude study drug absorption * No active peptic ulcer disease Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No ongoing or active infection * No poorly controlled diabetes mellitus * No other uncontrolled illness * No prior allergic reactions to compounds of similar chemical or biological composition to perifosine * No psychiatric illness or social situation that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * No more than 2 prior lines of chemotherapy for advanced disease, excluding adjuvant chemotherapy * Prior adjuvant chemotherapy allowed * At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered Endocrine therapy * At least 4 weeks since prior endocrine therapy * Multiple lines of endocrine therapy for advanced disease allowed Radiotherapy * At least 4 weeks since prior radiotherapy and recovered * Prior radiotherapy for metastatic disease allowed Surgery * No prior major gastric surgery * Prior surgery, including for metastatic disease, allowed Other * No other concurrent anticancer or investigational agents * No concurrent antiretroviral therapy in HIV-positive patients * Concurrent bisphosphonates allowed
Countries
Canada
Outcome results
None listed