Using Genomic Analysis to Guide Individual Treatment in Glioblastoma

Glioblastoma Clinical Trial

Official title:

Using Genomic Analysis to Guide Individual Treatment in Glioblastoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02725684
• Other study ID #: RDA-0837
• Status: Completed
• Phase: N/A
• First received: December 8, 2015
• Last updated: October 23, 2017
• Start date: March 12, 2015
• Est. completion date: July 7, 2017

Study information

• Verified date: October 2017
• Source: Rockefeller University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: July 7, 2017
• Est. primary completion date: July 7, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Glioblastoma

Intervention

Other:
• Observational study, no intervention
Observational study, no intervention

Locations

Country	Name	City	State
United States	Lenox Hill Hospital	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	New York University Langone Medical Center	New York	New York
United States	North Shore University Hospital	New York	New York
United States	Rockefeller University	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Montefiore Medical Center	The Bronx	New York

Sponsors (8)

Lead Sponsor	Collaborator
Rockefeller University	Albert Einstein College of Medicine, Inc., Lenox Hill Hospital, Memorial Sloan Kettering Cancer Center, New York Genome Center, New York University Langone Medical Center, North Shore University Hospital, Weill Medical College of Cornell University

Country where clinical trial is conducted

United States, 

References & Publications (3)

Gormally E, Caboux E, Vineis P, Hainaut P. Circulating free DNA in plasma or serum as biomarker of carcinogenesis: practical aspects and biological significance. Mutat Res. 2007 May-Jun;635(2-3):105-17. Epub 2007 Jan 25. Review. — View Citation

Hegi ME, Diserens AC, Godard S, Dietrich PY, Regli L, Ostermann S, Otten P, Van Melle G, de Tribolet N, Stupp R. Clinical trial substantiates the predictive value of O-6-methylguanine-DNA methyltransferase promoter methylation in glioblastoma patients treated with temozolomide. Clin Cancer Res. 2004 Mar 15;10(6):1871-4. — View Citation

Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identification of targetable variants in the tumor	Identification of variants in each tumor that are potential drug targets	6 months

External Links

•   Wetterstrand KA. DNA Sequencing Costs: Data from the NHGRI Genome SequencingProgram (GSP)