Phase II Study of Sunitinib Malate for Metastatic and/or Surgically Unresectable Soft Tissue Sarcoma
Condition: Liposarcoma; Leiomyosarcoma; Fibrosarcoma; Malignant Fibrous Histiocytoma
MeSH terms: Sarcoma; Leiomyosarcoma; Liposarcoma; Fibrosarcoma; Histiocytoma; Histiocytoma, Benign Fibrous; Histiocytoma, Malignant Fibrous
Intervention: Sunitinib Malate (SU011248)
Intervention description: For each 6 week cycle, patients will take SU011248 every day in the morning for 4 weeks followed by a 2 week rest period.
Intervention MeSH terms: Sunitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 48.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Sunitinib malate; SUTENT; SU011248; Soft tissue sarcoma; Gastrointestinal stromal tumors (GIST); MFH; Tyrosine kinase inhibitor; Imatinib mesylate; Phase II

Summary:

      This is an open label single site Phase II clinical trial to identify a potentially promising
      therapy dose for Sunitinib malate. The study drug will be taken orally once daily on days 1
      through 28 of each 42 day cycle. Treatment will be continued until there is either disease
      progression or cumulative/acute toxicity.

      All patients with unresectable or metastatic soft tissue sarcoma (STS): leiomyosarcoma,
      liposarcoma, fibrosarcoma, and malignant fibrous histiocytoma (MFH) seen at the Moffitt
      Cancer Center will be screened for eligibility to be enrolled in the study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Resolution of all acute toxic effects of prior chemotherapy or radiotherapy or
             surgical procedures to National Cancer Institute (NCI) Common Terminology Criteria for
             Adverse Events (CTCAE) Version 3.0 grade less than or equal to 1.

          -  Adequate organ function as defined by the following criteria:

               -  Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) less than
                  or equal to 2.5 x local laboratory upper limit of normal (ULN), or AST and ALT
                  less than or equal to 5 x ULN if liver function abnormalities are due to
                  underlying malignancy

               -  Total serum bilirubin less than or equal to 1.5 x ULN

               -  Absolute neutrophil count (ANC) greater than or equal to1500/microL

               -  Platelets greater than or equal to 100,000/microL

               -  Hemoglobin greater than or equal to 9.0 g/dL

               -  Serum calcium less than or equal to 12.0 mg/dL

               -  Serum creatinine less than or equal to 1.5 x ULN

          -  Histologically-proven liposarcoma, leiomyosarcoma, fibrosarcoma, or MFH

          -  Measurable disease radiographically

          -  Disease that is deemed surgically unresectable and/or metastatic

          -  Age greater than or equal to 18 years

          -  Life expectancy greater than 16 weeks

          -  Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2

          -  Patients may have had up to 3 prior chemotherapies within 4 weeks of starting the
             study treatment.

        Exclusion Criteria:

          -  Major surgery or radiation therapy or chemotherapy within 4 weeks of starting the
             study treatment.

          -  NCI CTCAE version 3 grade 3 hemorrhage within 4 weeks of starting the study treatment.

          -  History of or known brain metastases, spinal cord compression, or carcinomatous
             meningitis, or evidence of symptomatic brain or leptomeningeal disease.

          -  Any of the following within the 6 months prior to study drug administration:

               -  myocardial infarction,

               -  severe/unstable angina,

               -  coronary/peripheral artery bypass graft,

               -  symptomatic congestive heart failure,

               -  cerebrovascular accident or transient ischemic attack, or pulmonary embolism

          -  Ongoing cardiac dysrhythmias of NCI CTCAE greater than or equal to grade 2

          -  Prolonged QTc interval on baseline electrocardiogram (ECG) > 500 msec.

          -  Hypertension that cannot be controlled by medications (>150/100 mm Hg despite optimal
             medical therapy)

          -  Prior tyrosine kinase inhibitor therapy

          -  Pre-existing thyroid abnormality with thyroid function that cannot be maintained in
             the normal range with medication

          -  Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
             (AIDS)-related illness or other active infection

          -  Concurrent treatment on another clinical trial, except supportive care or
             non-treatment trials

          -  Concomitant use of agents known to induce or inhibit CYP3A4

          -  Concomitant use of agents metabolized by the cytochrome P450 system

          -  Ongoing treatment with therapeutic doses of Coumadin (low dose Coumadin up to 2 mg by
             mouth [PO] daily for thrombo-prophylaxis is allowed)

          -  Pregnancy or breastfeeding patients

          -  Other severe acute or chronic medical or psychiatric condition or laboratory
             abnormality that may increase the risk associated with study participation or study
             drug administration, or may interfere with the interpretation of study results, and in
             the judgment of the investigator would make the subject inappropriate for entry into
             this study.