Patient case: 26-year-old male with Liposarcoma. Genetic variant: MDM2 Amplification. Other conditions: None.

Clinical trial: S0505 Sorafenib in Treating Patients With Advanced Soft Tissue Sarcomas

Summary: 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.

Detailed description: 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: 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

Relevance to patient case: not relevant