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)
* Patients who have had chemotherapy, surgery, or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study are not eligible
* Patients may not be receiving any other investigational agents
* Patients cannot be receiving enzyme-inducing anti-epileptic drugs (EIAEDs)

  * If previously treated with EIAEDs, patients must have been switched to non-EIAEDs 4 weeks prior to starting RO4929097
  * Enzyme-inducing antiepileptic drugs (EIAEDs) include: carbamazepine (Tegretol); oxcarbazepine (Trileptal); phenobarbital (or derivatives); phenytoin (Dilantin)
  * 3.1.10.2 Non enzyme-inducing Antiepileptic Drugs (Non-EIAEDs) include: clobazam (Frisium); clonazepam (Rivotril); gabapentin (Neurontin); levetiracetam (Keppra); lamotrigine (Lamictal); topiramate (Topamax)
* No concurrent medications that are strong inducers/inhibitors or substrates of CYP3A4

  * Even though dexamethasone is a moderate inducer of CYP3A4, patients may remain on dexamethasone at the lowest dose possible
* Stable or decreasing steroid dose within 5 days prior to registration required
* No medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin®)
* No other investigational or commercial agents or therapies may be administered with the intent to treat the patient's malignancy
* No re-irradiation (any technique) is allowed
* If a patient elects to have a new resection of his/her tumor in the absence of progression of the disease, treatment will be discontinued and no re-challenge will be allowed after this additional surgery