RO4929097 in Treating Patients With Recurrent Invasive Gliomas

Inclusion Criteria

• •Patients must have radiographic progression of a histologically confirmed glioblastoma, high-grade astrocytoma, NOS, anaplastic mixed oligo-astrocytoma, or anaplastic oligodendroglioma
• •* In patients that present radiographic evidence of progression after concurrent treatment with radiation and low-dose temozolomide, diagnosis of progression should be made after at least 2 cycles of monthly temozolomide in order to rule out pseudoprogression
• •* Secondary MGs (evolving from a prior low-grade glioma) can be included as long as they are considered malignant in the latest resection
• •Patients must have at least one enhancing lesion that can be accurately measured as \> 1 X 1 cm on a MRI
• •Prior treatment must include radiotherapy (with or without temozolomide)
• •* No limit to the number of prior recurrences or surgeries
• •For Part B only, surgical resection should be considered a reasonable therapeutic option for a patient that can tolerate surgical resection
• •* Patients with multifocal disease can be included as long as resection is considered a reasonable option to manage the nodule that is progressing
• •* There must be sufficient tissue available (minimum from a 1 X 1 cm lesion) for a biopsy to be taken during surgery
• •There must be sufficient tissue available for evaluation of p75\^NTR status from a prior surgery (using immunohistochemistry on fixed tissue or, in uncommon cases in which frozen tissue is available from a prior surgery, western blot) (part B)
• •ECOG performance status \< 2 (Karnofsky \> 50%)
• •Life expectancy of greater than 4 weeks
• •Absolute neutrophil count \> 1,500/mcL
• •Platelets \> 100,000/mcL
• •Hemoglobin \> 90 g/L (or \> 9 g/dL)
• •Total bilirubin \< 2.0 mg/dL
• •BUN \< 25 mg/dL
• •AST/ALT \< 3 X institutional upper limit of normal
• •Creatinine within institutional normal limits OR creatinine clearance \> 60 mL/min
• •No major medical illnesses or psychiatric impairments that, in the investigator's opinion, would prevent administration or completion of protocol therapy
• •Not pregnant or nursing
• •Negative serum pregnancy test
• •Fertile patients must use two forms of contraception (i.e., barrier contraception and one other method of contraception) at least 4 weeks prior to study entry, during, and for 12 months after completion of study therapy
• •Able to swallow pills
• •Patients with a history of seizures need to have had no generalized seizures in the last month prior to entering the study
• •No history of allergic reactions attributed to compounds of similar chemical or biologic composition to RO4929097
• •No malabsorption syndrome or other condition that would interfere with intestinal absorption
• •Patients who are serologically positive for hepatitis A, B, or C, and have a resulting positive serological test, or have a history of liver disease, other forms of hepatitis, or cirrhosis are ineligible
• •No uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia, or hypokalemia (within 7 days prior to study treatment), despite adequate electrolyte supplementation
• •No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia other than chronic, stable atrial fibrillation, or psychiatric illness/social situations that would limit compliance with study requirements
• •HIV-positive patients on combination antiretroviral therapy are ineligible
• •Baseline QTc ≤ 450 msec (male) or QTc ≤ 470 msec (female)
• •No history of risk factors for QT interval prolongation, including, but not limited to, family or personal history of long QT syndrome, recurrent syncope without known etiology, or sudden unexpected death
• •No history of torsades de pointes or other significant cardiac arrhythmias or the need for concomitant meds with known potential to prolong QT interval or antiarrhythmics
• •Use of food that may interfere with the metabolism of RO4929097 is prohibited, including grapefruit or grapefruit juice
• •Patients must have recovered from the effects of any prior treatment (systemic chemotherapy/radiotherapy) or surgery (\<CTCAE grade 2 toxicities related to prior therapy)