DISEASE CHARACTERISTICS:

• Histologically confirmed soft-tissue sarcoma at original diagnosis meeting 1 of the following criteria:

  • Metastatic (de novo or recurrent) disease
  • Locally advanced unresectable disease
  • Gastrointestinal stromal tumor (GIST) subtype allowed
  • No pediatric-type sarcomas (e.g., Ewing's or primitive neuroectodermal tumor, rhabdomyosarcoma, and desmoplastic small round cell tumor)
• Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20 mm by conventional techniques or as ≥ 10 mm by spiral CT scan
• Patients with CNS tumors must have been on a stable or decreasing dose of dexamethasone for more than 7 days
• No known brain metastases

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-2 (Karnofsky PS 60-100%)
• Life expectancy > 12 weeks
• ANC ≥ 1,000/μL
• Platelet count ≥ 100,000/μL (transfusion independent)
• Hemoglobin ≥ 8.0 mg/dL (may receive red blood cell transfusions)
• Creatinine ≤ 1.5 times upper limit of normal (ULN) OR creatinine clearance ≥ 45 mL/min
• Bilirubin (sum of conjugated plus unconjugated) ≤ 1.5 times ULN
• ALT ≤ 5 times ULN
• Serum albumin ≥ 2 g/dL
• Fertile patients must use effective contraception during and for 4 weeks (women) or for 16 weeks (men) after completion of last dose of treatment
• Negative pregnancy test
• Not pregnant or nursing
• No evidence of dyspnea at rest and/or exercise intolerance
• Pulse oximetry > 94% if there is clinical indication for determination
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to MEK inhibitor AZD6244
• No QTc interval > 450 msecs, other factors that increase the risk of QT prolongation, or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome)
• Able to swallow capsules
• No refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption

• No uncontrolled intercurrent illness including, but not limited to, any of the following:

  • Ongoing or active infection
  • Psychiatric illness and/or social situations that would limit compliance with study requirements
• No patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study

• None of the following:

  • Cardiac history of uncontrolled hypertension
  • NYHA class II-IV cardiac disease
  • Prior or current cardiomyopathy
  • Baseline LVEF < 50%
  • Ongoing atrial fibrillation
  • Recent myocardial infarction
  • Unstable ischemic heart disease

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Up to 2 prior cytotoxic chemotherapeutic regimens (single-agent or combination of chemotherapies) for metastatic or recurrent disease allowed
• At least 1 week since prior growth factors that support platelet or white cell number or function
• At least 3 weeks since prior chemotherapy or radiotherapy (6 weeks for mitomycin C and nitrosoureas)
• No prior MEK inhibitor(s)
• No prior mTOR inhibitor for recurrent soft-tissue sarcoma
• No concurrent growth factor(s) that support platelet or white cell count or function within the past 7 days
• No other concurrent investigational drug
• No other concurrent anticancer agents including chemotherapy, radiotherapy, immunotherapy, or biologic therapy
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent strong CYP1A2 or CYP3A4 inducers and/or inhibitors