Phase II Study of RO4929097 (NSC-749225) in Advanced Melanoma

Histologically confirmed melanoma of cutaneous or uknown origin (ocular primary and mucosal primary excluded). Must undergo CT or MRI within 42 days prior to registration that is negative for brain disease. Must have measurable disease documented by physical exam, CT or MRI scan. Measurable disease must be assessed withing 28 days prior to registration. Must offer all patients participation in translational medicine studies and banking of paraffin embedded tissue and whole blood in Sections 15.1-15.2b. Must not have receieved any prior systemic therapy for Stage IV disease except for noncytologic biologic agents (e.g. vaccines, cytokines, cell therapies that do not require cytotoxic agents). May have received prior treatment with up to two prior biological therapies - no cytotoxiMay have had prior adjuvant immunotherapy with biological response modifiers. Prior adjuvant immunotherapy must have been completed at least 28 days prior to registration. Adjuvant therapy containing cytotoxic agents is allowed if completed >/= 180 days prior to registration. May have received prior radiation therapy. Any side effects the patients had due to prior radiation therapy must have resolved to </= Grade 1 prior to registration. Prior radiation therapy must have been completed at least 28 days prior to registration. May have received prior surgery (for both primary and Stage IV disease). Side effects patients had due to prior surgery must have resolved to </= Grade 1 prior to regisration. Prior surgery must have been completed at least 28 days prior to registration. Must have Zubrod performance status of 0-1. Must have adequate bone marrow function as evidenced by all of the following: leukocytes >/= 3,000/mcL; ANC >/= 1,500/mcL; platelets >/= 100,000 mcL; hemoglobin >/= 9 g/dL. These results must be obtained within 28 days prior to registration. Must have adequate liver function by both of following: total bilirubin </= IULN; AST or ALT </= 2.5 x IULN. These results must be obtained 28 days prior to registration. Must have adequate renal function by one of following: serum creatinine </= IULN or measured or calculated creatinine clearance >/= 60mL/min. Results must be obtained 28 days prior to registration. Patients must have the following serum electrolytes within the institutional ranges of normal: potassium, sodium, magnesium, phosphorus, chloride, and calcium (corrected for serum albumin). These tests must be performed within 28 days prior to registration. Patient must not require parenteral replacement therapy. Must not have a history of allergic reaction to compounds of similiar or biologic composition to RO4929097. Must be able to swallow tablets. Must not have malabsorption syndrome or other condition that would interfere with intestinal absorption of agent. Patients taking medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin) are ineligible. Must not be taking strong inducers or strong inhibitors of CYP3A4 (See Appendix 19.3a and 19.3c) at time of registration. Must not be serologically positive for Hepatitis A,B,C or have a history of liver disease, other forms of hepatitis or cirrhosis. Must have an ECG within 28 days of registration. Must not have a QTcF > 450 msec (males) or QTcF > 470 msec (females). Patients must not have symptomatic congestive heart failure or unstable angina pectoris. Patients with a history or torsades de pointes or any significant cardiac arrhythmia (except asymptomatic unifocal ventricular beats or supraventricular tachycardia easily controlled with oral medications) are excluded. Any patient requiring or expected to require antiarrhythmics or other therapy known to prolong QTc is also excluded (see Appendix 19.6 for list of agents). Must be >/= 18 years old. No other prior malignancy is allowed except for: adequately treated basal cell or squamous cell skin cancer., in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission or any other cancer from which the patient has been disease free for 5 years. Women of child bearing potential must have a negative pregnancy test within 14 days prior to registration (the type of pregnancy test used is at the discretion of the registering insitution). Female patients of childbearing potential include the following: Patients with regular menses; Patients, after menarche with amenorrhea, irregular cycles, or using a contraceptive method that precludes withdrawal bleeding; Women who have had tubal ligation. Women must not be nursing.