No eligibility information available.

* *Evidence of tumor progression by MRI or CT scan following RT or following the most recent anti-tumor therapy
*Bidimensionally measurable or evaluable disease by MRI or CT scan
*No prior intratumoral chem, stereotactic, radiosurgery or interstitial brachytherapy unless there is a seperate lesion on MRI which is not part of the previous tx field or there is proof of recurrnet disease based on biopsy, MRI spectroscopy, or PET scan
*No prior CCI-779, sorafenib or other agents specifically targeting mTOR, raf, or VEGF/VEGFR
*No un-controlled hypertension.
*No other active malignancy
*No uncontrolled active infection, congextive heart failure, cardiac arrhythmia, angina pectoris.


*

**Study 1, Arm C (EIAC’s patients) has met accrual to cohort 3. Therefore
Study 1, Arm C (EIAC’s patients) is temporarily suspended to patient accrual effective immediately, February 1, 2008. Patient entry will not be permitted until further notification is issued.**

Study 2 and study 3 are still open to accrual.


1)Histological confirmation of grade 2-4 oligodendroglioma, or mixed

oligoastrocytoma grade 2-4 containing oligodendrogliomatous component on central path review prior to study registration & a diagnosis of recurrence.
2)Measurable or revaluable disease by MRI or CT scan. Unequivocal evidence of tumor progression by MRI or CT performed less than or equal to 21 days prior to study registration.
3)Prior surgery & radiotherapy(RT)failed. Greater than or equal to 12 wks since completion of RT.
4)Must have received less than or equal to 2 total prior chemotx regimens, & less than or equal to 1 for relapsing disease.
5)ECOG PS - 0,1 or 2. No warfarin therapy. No other active malignancy.

*** SPECIAL REGS REQUIRED PRIOR TO PATIENT ENTRY *** (see section 6.0).

1. One to three presumed brain metastases from a histologically confirmed extracerebral tumor site (e.g. lung, breast, prostate, etc.). The histologic
confirmation may have been from the primary tumor site, from another
metastatic site (e.g. an osseous metastasis, adrenal metastasis, etc.), or from the metastatic brain lesion(s). NOTE: Each lesion must measure <3.0 cm in maximal extent on the contrasted pretreatment MRI brain scan obtained =21 days prior to randomization (see Magnetic Resonance Imaging (MRI) Guidelines section 11.2).

2. All standard tumor-staging procedures necessary to define baseline extracranial disease status completed =42 days prior to pre-registration.

3. Ability to be treated with either a gamma knife or a linear accelerator-based radiosurgery system. Note: A treating center must have completed stereotactic radiosurgery credentialing (see section 6.1).

4. =18 years of age.

5. Ability to complete questionnaire(s) by themselves or with assistance.

6. ECOG performance status 0, 1, or 2. For reference see
https://ncctg.mayo.edu/ncctg/formsNonProtocolSpecificForms/

7. Grooved peg board available for Neurocognitive Testing (See Section 6.29 for
further details). Note: The examiner must have credentialing confirming
completion of the neurocognitive testing training (see section 6.1)

Pre-Registration Contraindications

1. Any of the following:

? Pregnant women

? Men or women of childbearing potential who are unwilling to employ adequate contraception

2. Pacemaker or other MRI non-compatible metal in the body.

3. Known allergy to gadolinium.

4. Prior resection of cerebral metastasis.

5. A lesion that is located =5 mm of the optic chiasm or within the brainstem.

6. Prior chemotherapy =7 days prior to pre-registration.

7. Prior cranial radiation therapy.

8. Primary germ cell tumor, small cell carcinoma, or lymphoma.

9. Leptomeningeal metastasis.

10. Clinical or radiographical evidence of systemic progression (other than the
study lesion(s), i.e. other than the brain metastases) within one month prior to randomization.

Randomization Required Characteristics (Step 2)

1. Planning MRI confirmed one to three lesions. Each lesion must measure < 3.0
cm in maximal extent on the contrasted planning MRI brain scan.

2. Negative urine or serum pregnancy test done =7 days prior to randomization,
for women of child bearing potential only.

DISEASE CHARACTERISTICS:

Histologically confirmed diagnosis of 1 of the following:

Glioblastoma multiforme (grade 4 astrocytoma)
Other grade 4 astrocytoma variants (e.g., giant cell)
Gliosarcoma
Newly diagnosed disease
Some patients may be registered on protocol NCCTG-947252
No oligodendrogliomas or oligoastrocytomas
PATIENT CHARACTERISTICS:

Inclusion criteria:

ECOG performance status 0-2
ANC = 1,500/µL
Hemoglobin = 9.0 g/dL
Platelet count = 100,000/µL
Total bilirubin = 2.5 x institutional upper limit of normal (ULN)
Serum total cholesterol < 350 mg/dL
Serum total triglycerides < 400 mg/dL
AST = 2.5 x ULN
Creatinine = 1.5 x ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 60 days after completion of study therapy
Must be willing to undergo 2 mandatory research PET or PET/CT scans (all MCR and MCJ patients in phase I and MCR only patients in phase II)
Must be willing to abstain from eating or drinking grapefruit or grapefruit juice during study treatment
Must be willing to forego foods high in fat content 2 hours prior to and up to 2 hours after completing everolimus therapy
Ability to understand and willingness to sign a written informed consent
Exclusion criteria:

Other active cancers requiring therapy to control disease or prior cancer diagnoses which pose a greater than 30% risk of death within the next 2 years
Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active uncontrolled peptic ulcer disease
Uncontrolled intercurrent illness including, but not limited to, any of the following:

Ongoing, uncontrolled, or active (acute or chronic) infection or disorder
Symptomatic congestive heart failure
Unstable angina pectoris
Cardiac arrhythmia
Psychiatric illness/social situations that would limit compliance with study requirements
Severely impaired lung function
Uncontrolled diabetes (fasting serum glucose > 2 x ULN) OR diabetes that would interfere with the performance of the FDG-PET/CT or FDG-PET scans
Liver disease (e.g., cirrhosis, chronic active hepatitis, chronic persistent hepatitis, or history of hepatitis B)
Known HIV positivity
Any history of allergy or intolerance to dacarbazine (DTIC)
Significant traumatic injury within the past 21 days
Severe allergy to sulfa medications
Inability to tolerate either intravenous pentamidine or levofloxacin
PRIOR CONCURRENT THERAPY:

Inclusion criteria:

At least 1 week, but no more than 6 weeks since prior surgical resection or biopsy
Must comply with antibiotic prophylaxis with either trimethoprim/sulfamethoxazole daily or 3 times per week OR pentamine IV monthly combined with daily levofloxacin
Exclusion criteria:

Prior chemotherapy for any brain tumor
Prior temozolomide or mTOR inhibitor therapies
Any prior cranial radiotherapy
Planned immunization with attenuated live vaccines during study period
At least 21 days since prior major surgery (excluding neurosurgical biopsy, resection of brain tumor, or treatment of immediate post-neurosurgical complication [e.g., intracranial hematoma])
Concurrent or prior treatment for this cancer with any other investigational agents
Concurrent enzyme-inducing anticonvulsants (EIACs) or other strong inducers of CYP3A4 (i.e., carbamazepine, phenytoin, phenobarbital/primidone, rifabutin, rifampin, or St. John's wort)
Concurrent therapeutic doses of warfarin

Low molecular weight heparin is allowed
Concurrent systematic leukocyte growth factors (e.g., G-CSF or GM-CSF), except for the treatment of severe neutropenia
Concurrent drugs or substances known to inhibit or induce CYP3A
Other concurrent chronic treatment with immunosuppressive agents except dexamethasone
Other concurrent anticancer agents
Concurrent live vaccines

DISEASE CHARACTERISTICS:

Histologically confirmed meningioma, meeting 1 of the following criteria:

Low-risk disease, as defined by the following:

Newly diagnosed, WHO grade I disease that was gross totally resected (Simpson's grade I, II, or III resection with no residual nodular enhancement on postoperative imaging) or subtotally resected (residual nodular enhancement or Simpson grade IV or V resection)
Intermediate-risk disease, as defined by the following:

Newly diagnosed, WHO grade II disease that was gross totally resected OR recurrent WHO grade I disease irrespective of the resection extent
High-risk disease, as defined by 1 of the following:

Newly diagnosed or recurrent WHO grade III disease of any resection extent
Recurrent WHO grade II disease of any resection extent
Newly diagnosed, WHO grade II disease that was subtotally resected
Patients with newly diagnosed disease must have had a histologic diagnosis within the past 6 months AND have undergone pre- and post-operative MRIs within the past 3 months
Patients with recurrent/progressive intermediate- or high-risk disease who have not undergone recent surgery must have documentation of recurrence or progression by MRI within the past 3 months
No extracranial or multiple meningioma and/or hemangiopericytoma
PATIENT CHARACTERISTICS:

Zubrod performance status 0-1
Negative pregnancy test (for patients enrolled in groups 2 or 3)
Fertile patients must use effective contraception (for patients enrolled in groups 2 or 3)
No other invasive malignancy within the past 3 years except for nonmelanoma skin cancer or carcinoma in situ of the breast, oral cavity, or cervix
No severe, active comorbidity including, but not limited to, any of the following:

Unstable angina and/or congestive heart failure requiring hospitalization
Transmural myocardial infarction within the past 6 months
Acute bacterial and/or fungal infection requiring IV antibiotics
Chronic obstructive pulmonary disease exacerbation or respiratory illness requiring hospitalization or that would preclude study treatment
Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
Known HIV positivity or AIDS, based upon the current CDC definition
No evidence of active connective tissue disorders (e.g., lupus erythematosus and/or scleroderma) (for patients enrolled in groups 2 or 3)
No other major medical illness or psychiatric impairment that, in the investigator's opinion, would preclude study treatment or informed consent
PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior radiotherapy to the scalp, cranium, brain, or skull base

**Pt must have MRI prior to step 1. This is not listed in eligibility until step 2. GMP**

Inclusion:
*Histologically proven diagnosis of glioblastoma or gliosarcoma (WHO grade IV) confirmed by central review prior to step 2 registration
*Tumor tissue that is determined by central path review prior to step 2 registration to be of sufficient size for analysis of MGMT status and determination of molecular profile.
-Patients must have at least 1 block of tumor tissue; submission of 2 blocks is strongly encouraged. At least 1 cubic centimeter of tissue composed primarily of tumor must be present.
-Cavitron ultrasonic aspirator-derived material is not allowed; fresh frozen tumor tissue acquisition is encouraged.
-Diagnosis must be made by surgical excision, either partial or complete
-The tumor tissue should be sent ASAP. It should be submitted by 4 weeks after the surgical procedure so that study registration and treatment can commence by the mandatory 5 week postop outer limit.
*The tumor must have a supratentorial component.
*H&P within 14 days prior to registration
*The patient must have recovered from the effects of surgery, postop infection, and other complications.
*A diagnostic contrast-enhanced MRI of the brain must be performed preop and postop prior to the initiation of radiotherapy. The postop scan must be performed within 28 days prior to study registration.
*An MRI or CT scan (potentially in addition to the postoperative scan) must be obtained within 1 week prior to registration and must not demonstrate significant postop hemorrhage defined as > 1 cm diameter of blood. If > 1 cm of acute blood is detected, the patient will be ineligible for this trial. The radiation planning MRI or CT scan may be used to determine presence of hemorrhage.
*Patients unable to undergo MR imaging because of non-compatible devices can be
enrolled, provided pre- and postop contrast-enhanced CT scans are obtained and are of sufficient quality. Preop and postop scans must be the same type.
*Documentation of steroid doses within 14 days prior to registration.
*KPS = 70
*CBC/differential obtained within 14 days prior to on study, with adequate bone marrow function defined by protocol
*Adequate renal and hepatic function, as defined by protocol
*Systolic blood pressure = 160 mg Hg or diastolic pressure = 90 mg Hg within 14 days prior to study
*EKG without evidence of acute cardiac ischemia within 14 days prior study
*PT INR < 1.4 for patients not on warfarin confirmed by testing within 14 days prior to study.
*Patients on full-dose anticoagulants must meet both of the following criteria:
-No active bleeding or pathological condition that carries a high risk of bleeding
-In-range INR (between 2 and 3) on a stable dose of oral anticoagulant or on a
stable dose of low molecular weight heparin

Exclusion
*Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for = 3 years.
*Recurrent or multifocal malignant gliomas
*Metastases detected below the tentorium or beyond the cranial vault.
*Prior chemo or radiosensitizers for cancers of the head and neck region; note that prior chemo for a different cancer is allowable, except prior temozolomide or bevacizumab. Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment are not permitted.
*Prior RT to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields.
*Severe, active co-morbidity, defined as follows:
-Unstable angina and/or CHF within the last 6 months
-Transmural MI within the last 6 months
-Evidence of recent MI or ischemia by the findings of S-T elevations of = 2 mm using the analysis of an EKG performed within 14 days of registration
-NYHA grade II or greater CHF requiring hospitalization within 12 months prior to registration
-History of stroke or TIA within 6 months
-Serious and inadequately controlled cardiac arrhythmia
-Significant vascular disease or clinically significant PVD
-Evidence of bleeding diathesis or coagulopathy
-Serious or non-healing w

***SPECIAL REGULATORY REQUIRED PRIOR TO PATIENT ENROLLMENT******
MINIMUM OF ONE STAFF PERSON FROM EACH SITE MUST BE CERTIFIED FOR COGNITIVE TESTING...CALL CC/P TEAM
1)Life expectancy of at least > 30 weeks. Karnofsky Performance Status must be > 60 or ECG 2.
2)No planned therapy, including surgery, brain radiation of any type, chemotherapy, or immunotherapy during the next 30 weeks.
3)Must have received a prior course of at least 30 Gy fractionated whole or partial brain irradiation for treatment of a primary brain tumor or metastatic disease to the brain.
4)Must have completed radiation > 6 months prior to enrollment and have no radiographic evidence of brain disease, or stable brain disease defined as no evidence of tumor progression in the 3 months prior to enrollment.
5)Patients who have undergone one or more treatments with single fraction stereotactic radiosurgery (SRS) in addition to whole or partial brain irradiation are eligible
6)For patients with brain metastases, no progressive extracranial primary or metastatic disease can be present; if extracranial primary or metastatic disease is present, it must be stable or have responded to local and/or systemic treatment in the 3 months prior to enrollment
7)No history of active peptic ulcer, active asthma, or active chronic obstructive pulmonary disease
8)No arrythmias including bradycardia or heartblock