Using Genomic Analysis to Guide Individual Treatment in Glioblastoma

The purpose of the study is to assess whether the use of genomics can identify patient
specific treatment choices in glioblastoma (GBM) that improves clinical outcomes over
standard of care. GBM is a devastating disease, the most common primary brain tumor and the
most aggressive. With current standard therapy, which includes surgery, radiation therapy,
and chemotherapy with temozolomide, the median survival is only 14.6 months. Once patients
fail temozolomide, there are no other proven therapies, although other chemotherapies,
bevacizumab, and tyrosine kinase inhibitors are often tried. Because tumors are different
between patients, outcomes vary among patients. For example, temozolomide, though recommended
to all patients with GBM as the only chemotherapy to improve survival, is also known not to
be effective in patients with o6-methylguanine-DNA-methyltransferase (MGMT) unmethylated
tumors. This example underscores the idea that if each tumor is different, and that perhaps
there would be better outcomes if each tumor was treated uniquely.

Genomic sequencing is a technology that can be employed to identify specific characteristics
of each tumor as compared to healthy cells. Since 2008, genomic sequencing technology has
advanced significantly, having entered the era of next generation sequencing, and
simultaneously, the cost of using this technology has dramatically decreased, nearing the
cost of some currently used diagnostic tests such as MRI. In this study, the investigators
plan to assess the usefulness of this technology and its analysis as a method of guiding
treatment choices for the individual patient with GBM.

The investigators plan to sequence tumor/normal from GBM patients to identify mutations. The
mutations will be analyzed for potential drug targets for treatment and recommendations for
treatment will be suggested if any are identified. If the clinician implements the
recommendations, clinical follow up data will be collected. The investigators will compare
clinical outcomes, such as survival to historical controls undergoing standard of care
treatment to assess whether this genomic guided, individualized therapy determination
improves these measures.

In addition, the investigators plan to use next generation sequencing methods to determine
whether the presence of brain messenger ribonucleic acid (mRNA) and miRNA can be detected in
the peripheral blood and whether there is biological relevance to their presence if detected.

Inclusion Criteria:

- Histologically confirmed glioblastoma multiforme

- Enough tumor tissue available from initial surgery to obtain at least 5 ug DNA and 5
ug RNA

- Sufficient blood sample to obtain 5 ug DNA and 5 ug RNA

- Karnofsky score at least 60

- Life expectancy at least 6 months

Exclusion Criteria:

- Subjects not interested in further treatment of their brain tumor