Patient case: 78-year-old female with sarcoma; genetic feature: MDM2

Clinical trial: Perifosine in Treating Patients With Metastatic or Locally Advanced Soft Tissue Sarcoma

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 metastatic or locally advanced soft tissue sarcoma.

Detailed description: 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.

Eligibility: 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

Relevance to patient case: not relevant