MK-2206 for Recurrent Malignant Glioma

- Participants will have the following tests and procedures within 2 days before the
first dose of MK-2206: medical history, physical examination, blood tests, urine tests
and EKG.

- Participants in Part 2 of this research study may also have optional FDG-PET imaging
done. If the participant agrees, they will have two PET scans performed; one within a
week before beginning study drug, and another within 3 days after starting study drug.

- Participants in Part 1 will take MK-2206 orally prior to surgery on days 1-8 (with
surgery after the MK-2206 dose on day 8). They will have an EKG within 4-8 hours after
their first dose of MK-2206, and again on Day 8. During surgery, a sample of the tumor
will be taken for research. The tumor tissue will be analyzed to measure the level of
MK-2206 in the tumor and to study the effect of the drug on the tumor. Genetic tests
will be done on the tumor tissue to determine if the tumor's genetic profile can
predict response to treatment. You will also have 3 teaspoons of blood drawn to measure
the level of MK-2206 in the blood. An assessment of the participant's tumor by MRI or
CT scan will be done within 96 hours of surgery to determine how much of the tumor has
been removed. One to 4 weeks after surgery (within 14 days of the last MRI/CT scan),
MK-2206 treatment will restart at the same schedule as before surgery (weekly dosing).
Within 2 days prior to restarting MK-2206 the following tests and procedures must be
completed: medical history, physical examination, blood tests, urine test and EKG.

- Participants in both groups will receive MK-2206 by mouth once a week (Days 1, 8, 15,
and 22). Participants will receive an EKG within 4-8 hours after their first dose of
MK-2206 (for Part 1 participants, this is day 1 pre-surgery; for Part 2 participants,
this is day 1 of the first cycle of treatment). Participants will receive an EKG weekly
during their first cycle of treatment with MK-2206. The following tests and procedures
are required within 2 days before the start of each subsequent 4-week cycle of MK-2206
treatment: medical history, physical examination, blood tests, urine test, and EKG.
Each treatment cycle lasts 4 weeks during which time participants will be taking the
study drug once a week. In addition, patients will also need the following
tests/procedures performed during treatment cycles: medical history and physical
examination on Day 15 (+/- 2 days) of Cycles 1 and 2 and blood tests weekly during
Cycle 1 and on Day 15 (+/- 2 days) of cycle 2.

- Assessments of the tumor by MRI will be performed within one week prior to the start of
each odd-numbered cycle, starting with cycle 3.

- Participants can continue to receive study drug until their disease worsens or develop
unacceptable side effects.

Inclusion Criteria:

- Histologically confirmed glioblastoma or gliosarcoma. Participants will be eligible
if the orginal histology was low-grade glioma and a subsequent histological diagnosis
of glioblastoma or gliosarcoma is made.

- Unequivocal evidence for tumor progression by MRI or CT scan. A scan should be
performed within 14 days of registration. The same type of scan must be used
throughout the period of protocol treatment for tumor measurement. MRI scans are
preferred whenever possible. If participants in Part 2 of the study are taking
corticosteroids, the dose must be stable or decreasing for at least 5 days prior to
the scan.

- Must have recovered from the toxic effects of prior therapy. From the start of
scheduled study treatment, the following time periods must have elapsed: 4 weeks from
any investigational agent, 4 weeks from cytotoxic therapy, or 4 weeks from other
anti-tumor therapies.

- Must have failed prior radiation therapy and must have an interval of at least 12
weeks from the completion of radiation therapy.

- Prior therapy that included interstitial brachytherapy or stereotactic radiosurgery
must have confirmation of progressive disease based upon nuclear imaging, MR
spectroscopy, or histopathology.

- Participants having undergone recent resection of recurrent or progressive tumor will
be eligible as long as the following conditions apply: a) they have recovered from
the effects of surgery, b) residual disease following resection of recurrent tumor is
not mandated for eligibility. To best assess the extent of residual disease
post-operatively, and MRI or CT scan should be done no later than 96 hours following
surgery or at least 4 weeks post-operatively, in either case within 14 days prior to
registration. If participants in Part 2 of the study are taking corticosteroids, the
dose must be stable or decreasing for at least 5 days prior to the scan. If steroids
are added or the steroid dose is increased between the date of the screening MRI or
CT scan and the start of treatment, a new baseline MRI or CT is required.

- 18 years of age or older

- Life expectancy of > 8 weeks

- Karnofsky performance status 60 or greater

- Normal organ and marrow function as outlined in the protocol

- At least 35-45 paraffin slides (standard thickness of 4 microns) from any prior
surgery available for correlative studies

- Women of child-bearing potential and men must agree to use adequate contraception
prior to study entry and for the duration of study participation.

- Participants must be registered for the Ivy Consortium Tissue and Data Study.

Additional Part 1 Eligibility Criteria:

- Must be deemed by the site Investigator to be an appropriate candidate for surgical
resection.

- Must have frozen tumor sample (minimum of 100mg of tissue) from any prior surgery
available for correlative studies

- Unequivocal evidence for tumor progression by MRI or CT scan. For this scan only,
increasing corticosteroid doses are acceptable.

Additional Part 2 Eligibility Criteria:

- Subjects with anaplastic gliomas who meet other eligibility criteria are eligible.

Exclusion Criteria:

- Participants who have received therapy for more than two prior relapses

- Prior treatment with Akt inhibitors, PI3K inhibitors, mTOR inhibitors, or
anti-angiogenic agents

- Must not be on an enzyme-inducing anti-epileptic drug. If previously on an EIAED, the
patient must be off of it for at least two weeks prior to registration.

- Receiving any medications or substances that are strong inhibitors or inducers of
CYP3A4

- Receiving any other investigational agents

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to MK-2206

- History or current evidence of heart disease

- Uncontrolled intercurrent illness including, but not limited to ongoing or active
infection, chronic liver disease, chronic renal disease, chronic pulmonary disease,
or psychiatric illness/social situations that would limit compliance with study
requirements.

- Poorly controlled diabetes mellitus

- Pregnant or breastfeeding women

- Individuals with a history of a different malignancy are ineligible except for the
following circumstances. Individuals with a history of other malignancies are
eligible if they have been disease-free for at least 3 years and are deemed by the
investigator to be at low risk for recurrence of that malignancy. Individuals with
the following cancers are eligible if diagnosed and treated within the past 3 years:
cervical cancer in situ, and basal cell squamous cell carcinoma of the skin

- HIV-positive individuals