Using Genomic Analysis to Guide Individual Treatment in Glioblastoma

Brief Summary
The purpose of this study is to assess whether the use of genomics can help identify patient specific treatment choices in cancer. In order to test this, the investigators plan to use genomic sequencing technology to identify patient specific mutations in glioblastoma multiforme (GBM) as compared to normal cells to identify mutations. Further analysis will identify potential treatment targets and whether there are any drugs that could be used for these particular mutations. Follow up clinical data will be assessed to see if this individualized method of choosing treatment options can improve clinical outcomes in patients with GBM.
Brief Title
Using Genomic Analysis to Guide Individual Treatment in Glioblastoma
Detailed Description
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.
Completion Date
Completion Date Type
Actual
Conditions
Glioblastoma
Eligibility Criteria
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
Inclusion Criteria
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

Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Submit Date
Maximum Age
100 Years
Minimum Age
3 Years
NCT Id
NCT02725684
Org Class
Other
Org Full Name
Rockefeller University
Org Study Id
RDA-0837
Overall Status
Completed
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Using Genomic Analysis to Guide Individual Treatment in Glioblastoma
Primary Outcomes
Outcome Description
Identification of variants in each tumor that are potential drug targets
Outcome Measure
Identification of targetable variants in the tumor
Outcome Time Frame
6 months
Start Date
Start Date Type
Actual
Status Verified Date
First Submit Date
First Submit QC Date
Study Population
Patients with glioblastoma
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
100
Minimum Age Number (converted to Years and rounded down)
3
Investigators
Investigator Type
Principal Investigator
Investigator Name
Jerome Graber
Investigator Email
jgraber@montefiore.org
Investigator Phone
718-920-5505