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

A Phase 2 Study of AZD0530 in Recurrent or Metastatic Soft Tissue Sarcoma

This phase II trial is studying how well AZD0530 works in treating patients with recurrent locally advanced, or metastatic soft tissue sarcoma. AZD0530 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

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