Inclusion Criteria:

- 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 computed tomography (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

- 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 toMEK 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

- No concurrent strong CYP1A2 or CYP3A4 inducers and/or inhibitors

- 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