S0505 Sorafenib in Treating Patients With Advanced Soft Tissue Sarcomas

RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well sorafenib works in treating patients with advanced soft tissue sarcomas.

OBJECTIVES:

* Determine the objective response rate (confirmed, complete, and partial) in patients with advanced soft tissue sarcomas treated with sorafenib.
* Determine the 4-month progression-free survival rate in patients treated with this drug.
* Determine the frequency and severity of adverse events in patients treated with this drug.

OTHER OBJECTIVES (if funding permits):

* Correlate, preliminarily, a decrease in standard uptake variable (SUV) of target lesions by positron-emission tomography scan at 4 weeks with response in patients treated with this drug.
* Correlate, preliminarily, the phosphorylation status of KIT, PDGFR, VEGFR, and the raf/mek/erk pathway with response in patients treated with this drug.
* Correlate, preliminarily, the most common B-raf kinase mutation with response in patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to histology (leiomyosarcoma vs liposarcoma vs angiosarcoma, hemangiosarcoma, or hemangiopericytoma).

Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 8 weeks until disease progression and then every 6 months for 2 years and annually for up to 3 years.

PROJECTED ACCRUAL: A total of 45-75 patients (15-25 per stratum) will be accrued for this study within 15-38 months.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically confirmed soft tissue sarcoma of 1 of the following histologies:

  * Angiosarcoma, cutaneous or visceral
  * Malignant hemangiosarcoma
  * Malignant hemangiopericytoma
  * Grade 3-4 leiomyosarcoma
  * Grade 3-4 liposarcoma
* Must have evidence of unresectable residual disease, metastatic disease, or recurrent disease by radiography
* Measurable disease by x-ray, scans, or physical examination
* Archived paraffin-embedded tumor sections available
* No known brain metastases

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* Zubrod 0-1

Life expectancy

* Not specified

Hematopoietic

* WBC ≥ 3,000/mm\^3
* Absolute neutrophil count ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3

Hepatic

* SGOT and SGPT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if due to liver metastases)
* Bilirubin normal (≤ 2.5 times ULN if due to liver metastases)
* PT, PTT, and INR normal

Renal

* Creatinine normal OR
* Creatinine clearance ≥ 60 mL/min

Cardiovascular

* No history of thromboembolic disease
* No uncontrolled hypertension

Other

* Not pregnant or nursing
* Fertile patients must use effective contraception
* Able to swallow oral medication
* No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* At least 28 days since prior chemotherapy (42 days for carmustine or mitomycin) and recovered
* Prior adjuvant chemotherapy allowed
* No more than 1 prior chemotherapy regimen for metastatic disease

Endocrine therapy

* Not specified

Radiotherapy

* At least 28 days since prior radiotherapy and recovered

  * Must have evidence of disease progression within, or measurable disease outside of, the radiation field after completion of radiotherapy

Surgery

* At least 28 days since prior major surgery and recovered

Other

* No prior sorafenib
* No prior inhibitor of VEGFR or MAPK pathway
* No concurrent combination antiretroviral therapy for HIV-positive patients
* No other concurrent investigational agents
* No concurrent therapeutic anticoagulation
* No concurrent administration of any of the following medications:

  * Rifampin
  * Hypericum perforatum (St. John's wort)
  * Cytochrome P450 enzyme-inducing antiepileptic drugs, including any of the following:

    * Phenytoin
    * Carbamazepine
    * Phenobarbital