A Phase I/II Study of Sunitinib and Dacarbazine

Exclusion Criteria

• •Major surgery or radiation therapy within 4 weeks of starting the study treatment.
• •NCI CTCAE grade 3 hemorrhage within 4 weeks of starting the study treatment.
• •History of or known carcinomatous meningitis, or evidence of symptomatic leptomeningeal disease on screening CT or MRI scan.
• •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 grade greater than or equal to 2.
• •QTc \>470 msec on baseline EKG.
• •History of active CHF or LVEF\<50% at screening echocardiogram.
• •Hypertension that cannot be controlled by medications (\>150/100 mm Hg despite optimal medical 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. Supportive care trials or non-treatment trials, e.g. QOL, are allowed.
• •Ongoing treatment with therapeutic doses of Coumadin (low dose Coumadin up to 2 mg po daily for thromboembolism prophylaxis is allowed).
• •Pregnancy or breastfeeding. Female subjects must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy. All female subjects with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrollment. Male subjects must be surgically sterile or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate.
• •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.
• •Patients may not have had previous treatment with a DTIC or temozolomide based chemotherapy regimen. In the Phase II part of the trial patients may not have had treatment with any chemotherapy regimen.