Clinical trial NCT02725684: Using Genomic Analysis to Guide Individual Treatment in Glioblastoma
Official title: Using Genomic Analysis to Guide Individual Treatment in Glioblastoma
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Glioblastoma
Lead sponsor: Rockefeller University
Sponsor class: OTHER
Collaborators: name: Memorial Sloan Kettering Cancer Center
name: Lenox Hill Hospital
name: North Shore University Hospital
name: NYU Langone Health
name: Weill Medical College of Cornell University
name: Albert Einstein College of Medicine
name: New York Genome Center
First posted: 2016-04-01
Enrollment: 36
Sex: ALL
Minimum age (years): 3
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with 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.

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.

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

Primary outcomes:
measure: Identification of targetable variants in the tumor
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Rockefeller University
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: New York
country: United States
facility: Lenox Hill Hospital
state: New York
city: New York
country: United States
facility: North Shore University Hospital
state: New York
city: The Bronx
country: United States
facility: Montefiore Medical Center
state: New York
Study officials:
affiliation: Rockefeller University
name: Robert Darnell, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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):105-117. doi: 10.1016/j.mrrev.2006.11.002. Epub 2007 Jan 25.
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. doi: 10.1158/1078-0432.ccr-03-0384.
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. doi: 10.1056/NEJMoa043330.
citation: Wrzeszczynski KO, Frank MO, Koyama T, Rhrissorrakrai K, Robine N, Utro F, Emde AK, Chen BJ, Arora K, Shah M, Vacic V, Norel R, Bilal E, Bergmann EA, Moore Vogel JL, Bruce JN, Lassman AB, Canoll P, Grommes C, Harvey S, Parida L, Michelini VV, Zody MC, Jobanputra V, Royyuru AK, Darnell RB. Comparing sequencing assays and human-machine analyses in actionable genomics for glioblastoma. Neurol Genet. 2017 Jul 11;3(4):e164. doi: 10.1212/NXG.0000000000000164. eCollection 2017 Aug.