AZD0530 in Treating Patients With Recurrent Locally Advanced or Metastatic Soft Tissue Sarcoma

OBJECTIVES:

I. To assess the efficacy of AZD0530, in terms of disease control rate (i.e., response rate
and stable disease rate), in patients with recurrent locally advanced or metastatic soft
tissue sarcoma.

II. To assess the toxicity, time to progression, and response duration of AZD0530 in these
patients.

OUTLINE: This is a multicenter study.

Patients receive oral AZD0530 once daily in the absence of disease progression or
unacceptable toxicity.

After completion of study therapy, patients are followed every 8 weeks.

Inclusion Criteria:

- Leukocytes >= 3,000/mcL

- Histologically or cytologically confirmed soft tissue sarcoma including, but not
limited to any of:

- Malignant fibrous histiocytoma

- Fibrosarcoma - non infantile

- Leiomyosarcoma - not uterine

- Liposarcoma

- Non-rhabdomyosarcoma soft tissue sarcoma

- Rhabdomyosarcoma, not otherwise specified

- Carcinosarcoma of the uterus

- Dermatofibrosarcoma

- Endometrial stromal sarcoma

- Leiomyosarcoma - uterus

- Recurrent or locally advanced or metastatic disease

- No more than two prior lines of chemotherapy for metastatic disease (not
including adjuvant chemotherapy)

- Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm by
conventional techniques or >= 10 mm by spiral CT scan

- Target measurable lesion must not have been in previous radiation portal, unless
progression of this lesion after radiotherapy has been documented

- ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%

- Life expectancy > 12 weeks

- Recovered from all prior therapy

- Platelet count >= 100,000/mcL

- Hemoglobin > 9 g/dL

- Total bilirubin =< 1.25 times upper limit of normal (ULN)

- AST and ALT =< 3 times ULN

- Creatinine =< 1.5 times ULN OR creatinine clearance >= 50 mL/min

- Urine protein:creatinine ratio =< 1.0 OR 24-hour urine protein < 1,000 mg

- ANC >1,500/mcL

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 8 weeks after
completion of study therapy

- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to AZD0530

- No QTc prolongation (defined as a QTc interval >= to 460 msecs) or other significant
ECG abnormalities

- No poorly controlled hypertension (i.e., systolic blood pressure (BP) >= 140 mm Hg, or
diastolic BP >= 90 mm Hg)

- No condition that impairs a patient's ability to swallow AZD0530 tablets, including
any of the following:

- Gastrointestinal tract disease resulting in an inability to take oral medication
or a requirement for IV alimentation

- Prior surgical procedures affecting absorption

- Active peptic ulcer disease

Exclusion Criteria:

- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)

- No intercurrent cardiac dysfunction including, but not limited to, any of the
following:

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- No history of ischemic heart disease, including myocardial infarction

- No uncontrolled intercurrent illness including, but not limited to ongoing or active
infection or psychiatric illness/social situations that would limit compliance with
study requirements

- More than 4 weeks since prior radiotherapy

- More than 7 days since prior and no concurrent prohibited CYP3A4-active agents or
substances

- No other concurrent investigational agents or commercial agents or therapies

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No known brain metastases