Perifosine in Treating Patients With Recurrent, Refractory, Locally Advanced, or Metastatic Breast Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 2 Study Of Perifosine In Metastatic Or Advanced Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: perifosine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: perifosine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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male breast cancer, recurrent breast cancer, stage IV breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer