OBJECTIVES:

• Determine the 6-month progression-free rate, time to progression, and survival of patients with advanced soft tissue sarcoma treated with perifosine.
• Determine the objective tumor response status and duration of response in patients treated with this drug.
• Determine the pharmacokinetics of this drug in these patients.
• Determine the patterns of treatment failure and adverse event rate in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive a loading dose of oral perifosine every 6 hours for a total of 4 doses on day 1 and once daily on days 2-28 of course 1 only. For all subsequent courses, patients receive oral perifosine once daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 5 years.

PROJECTED ACCRUAL: A total of 17-46 patients will be accrued for this study within 9-12 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed advanced soft tissue sarcoma

• Measurable disease

  • Lesions that have been previously irradiated must have progressed at least 25% since prior radiotherapy

• No uncontrolled brain metastases

  • Previously treated brain metastases are allowed provided they are controlled for more than 8 weeks prior to study entry

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than upper limit of normal (ULN)
• AST no greater than 2.5 times ULN

Renal

• Creatinine no greater than ULN OR
• Creatinine clearance at least 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No symptomatic cardiac arrhythmia despite appropriate therapy

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior allergic reactions attributed to compounds of similar chemical or biological composition to perifosine
• No other concurrent uncontrolled illness
• No ongoing or active infection
• No psychiatric illness or social situations that would preclude study compliance
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or noninvasive carcinoma

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 4 weeks since prior biologic therapy
• More than 4 weeks since prior immunotherapy
• No concurrent immunotherapy
• No concurrent immunomodulating agents

Chemotherapy

• No more than 2 prior cytotoxic chemotherapy regimens for metastatic sarcoma
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• More than 4 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery

• Not specified

Other

• Recovered from prior therapy
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent commercial or other investigational agents or therapies for the malignancy
• No other concurrent cytostatic or cytotoxic agents