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 metastatic or locally advancedsoft tissue sarcoma.

Condition	Treatment or Intervention	Phase
adult soft tissue sarcoma uterine sarcoma	Drug: perifosine  Procedure: chemotherapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the efficacy of perifosine, in terms of response rate and duration of response, in patients with untreated metastatic or locally advanced soft tissue sarcoma.
• Determine the toxicity of this drug in these patients.
• Determine the early progression rate in patients treated with this drug.

OUTLINE: This is a non-randomized, non-blinded, multicenter study.

Patients receive a loading dose of oral perifosine twice on day 1 and then once daily on days 2-21 for the first course. For all subsequent courses, patients receive a loading dose of oral perifosine once on day 1 and then once daily on days 2-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed for 1 month. Patients with stable or responsive disease are followed every 3 months thereafter.

PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 12-18 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic or locally advanced soft tissue sarcoma that is incurable by standard therapies, including any of the following types:
• Uterine sarcomas
• Mixed mesodermal
• Leiomyosarcoma
• Endometrial stromal sarcoma
• Alveolar soft part sarcoma
• Angiosarcoma/lymphangiosarcoma
• Fibrosarcoma
• Hemangiopericytoma
• Leiomyosarcoma
• Liposarcoma
• Malignant fibrous histiocytoma
• Neurogenic sarcoma
• Pleomorphic rhabdomyosarcoma
• Synovial sarcoma
• Unclassifiable sarcoma
• Undifferentiated sarcoma
• Excluded diseases include the following:
• Bone sarcomas (e.g., osteosarcoma, Ewing's sarcoma, chondrosarcoma)
• Embryonal rhabdomyosarcoma
• Carcinosarcoma
• Kaposi's sarcoma
• Malignant mesothelioma
• Neuroblastoma
• Gastrointestinal stromal tumor
• At least 1 unidimensionally measurable site of disease (outside the previously irradiated area) defined as:
• At least 20 mm by x-ray or physical exam
• At least 10 mm by spiral CT scan
• At least 20 mm by non-spiral CT scan NOTE: Bone lesions are not considered measurable

NOTE: Patients whose sole site of disease is within a previously irradiated area are allowed if there is evidence of progression or new lesions in the irradiated field

• No known brain metastases

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute granulocyte 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

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

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 malignancy within the past 5 years except adequately treated nonmelanoma skin cancer or curatively treated carcinoma in situ of the cervix
• No active or ongoing infection
• No psychiatric illness or social situation that would limit compliance with study requirements
• No other concurrent uncontrolled illness

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• No prior systemic chemotherapy for metastatic or locally advanced disease
• At least 6 months since prior adjuvant chemotherapy
• No other concurrent cytotoxic chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy (except low-dose, non-myelosuppressive radiotherapy)
• No concurrent radiotherapy to the sole site of measurable disease or for progressively symptomatic disease

Surgery

• At least 4 weeks since prior major surgery

Other

• No other concurrent anticancer therapy or investigational agents

Canada, Alberta
      Tom Baker Cancer Center - Calgary, Calgary,  Alberta,  T2N 4N2,  Canada
Canada, British Columbia
      British Columbia Cancer Agency - Vancouver Island Cancer Centre, Vancouver,  British Columbia,  V5Z 4E6,  Canada
Canada, Ontario
      Cancer Care Ontario-London Regional Cancer Centre, London,  Ontario,  N6A 4L6,  Canada
      Margaret and Charles Juravinski Cancer Centre, Hamilton,  Ontario,  L8V 5C2,  Canada
      Mount Sinai Hospital - Toronto, Toronto,  Ontario,  M5G 1X5,  Canada
Canada, Quebec
      Maisonneuve-Rosemont Hospital, Montreal,  Quebec,  H1T 2M4,  Canada

Study chairs or principal investigators

Margaret Anne Knowling, MD,  Study Chair,  British Columbia Cancer Agency   

Study ID Numbers:  CDR0000269476; CAN-NCIC-IND155
Record last reviewed:  May 2004
Last Updated:  October 13, 2004
Record first received:  February 5, 2003
ClinicalTrials.gov Identifier:  NCT00053794
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08