A Multicenter Phase II Study of Continuous Dosing of Sunitinib (Sutent®, SU11248) in Non-GIST Sarcomas
A Multicenter Phase II Study of Continuous Dosing of Sunitinib (Sutent®, SU11248) in Non-GIST Sarcomas
RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
PURPOSE: This phase II trial is studying how well sunitinib works in treating patients with metastatic, locally advanced, or locally recurrent sarcomas.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter study. Patients are stratified by neoplastic subtype (vascular connective tissue neoplasms, leiomyosarcoma, dermatofibrosarcoma protuberans, chordoma, or desmoid tumors vs high-grade undifferentiated pleomorphic sarcoma [i.e., malignant fibrous histiocytoma (including myxofibrosarcoma)], or other nongastrointestinal connective tissue tumors [including carcinosarcomas]).
Patients receive oral sunitinib malate once daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed periodically.
DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed connective tissue neoplasm, including any of the following neoplastic subtypes:
Metastatic, locally advanced, or locally recurrent disease
Measurable disease
No gastrointestinal stromal tumor sarcomas
Prior standard neoadjuvant or adjuvant systemic therapy required for patients with the following diagnoses:
No untreated brain metastases, spinal cord compression, or evidence of symptomatic brain metastases or leptomeningeal disease as documented on screening CT scan or MRI
PATIENT CHARACTERISTICS:
ECOG performance status 0-2
Absolute neutrophil count ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Bilirubin ≤ 1.5 mg/dL
PT and INR ≤ 1.5
AST and ALT ≤ 2.5 times upper limit of normal
Creatinine ≤ 1.5 mg/dL
Calcium ≤ 12 mg/dL
Blood glucose < 150 mg/dL
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception prior to, during, and for 28 days after completion of study therapy
Other malignancies allowed provided sarcoma is the primary disease requiring systemic therapy
Able to swallow oral medications
No other disease or illness within the past 6 months, including any of the following:
No evidence of a bleeding diathesis
No ongoing cardiac dysrhythmias > grade 2
No uncontrolled hypertension, defined as blood pressure > 150/100 mm Hg despite optimal medical therapy
Left ventricular ejection fraction ≥ 50% by echocardiogram or MUGA scan
No psychiatric illness or social situation that would preclude study compliance
No pre-existing thyroid abnormality, defined as abnormal thyroid function tests despite medication
No prolonged QTc interval (i.e., QTc > 450 msec for males or QTc > 470 msec for females) on baseline EKG
No hemorrhage ≥ grade 3 in the past 4 weeks
PRIOR CONCURRENT THERAPY:
See Disease Characteristics
Recovered from prior therapy
No prior sunitinib malate
No more than 3 prior cytotoxic chemotherapy regimens for metastatic disease
At least 2 weeks since prior cytotoxic chemotherapy
At least 6 weeks since prior carmustine or mitomycin C
At least 1 week since prior biological therapy or small molecule kinase inhibitors
At least 3 weeks since prior radiotherapy (except for palliative radiotherapy to specific sites)
More than 4 weeks since prior major surgery
Concurrent major surgery allowed provided study drug is stopped 2 weeks before surgery and resumed 2 weeks after surgery
Concurrent palliative radiotherapy (e.g., focal radiotherapy to a bony metastasis for relieving bone pain) allowed
No other concurrent investigational drugs
No concurrent participation in another clinical trial
No concurrent therapeutic anticoagulation (e.g., warfarin)
No other concurrent approved or investigational anticancer agents or treatment, including chemotherapy, biological response modifier therapy, hormonal therapy, or immunotherapy
No concurrent antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital)
No concurrent rifampin, theophylline, ketoconazole, or Hypericum perforatum (St. John's wort)