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

A Phase II Study Of Perifosine (D-21266) In Patients With Previously Untreated Metastatic Or Locally Advanced Soft Tissue Sarcoma

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.

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.

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