Cytochrome C Oxidase Activity in Newly Diagnosed Glioblastoma Multiforme (GBM)
- Conditions
- Glioblastoma
- Registration Number
- NCT02997423
- Lead Sponsor
- University of Iowa
- Brief Summary
This is a multi-institutional, consortium-based, non-interventional prospective blinded endpoints clinical study to determine whether high activity of Cytochrome C Oxidase (CcO) in tumor specimens from subjects with newly diagnosed primary GBM is associated with shortened OS (primary outcome) and PFS (secondary outcome) times.
- Detailed Description
This Biomarker trial is designed to prospectively evaluate the hypothesis that the overall survival (OS) time of a subject with newly diagnosed primary GBM tumors, treated by standard of care (SOC), is a function of the CcO enzymatic activity in the tumor (OS; time interval from date of first diagnosis to death from any cause, irrespective of post-SOC therapies, assessed up to 24 months from accrual). In particular, tumors with high CcO activity are associated with shorter OS time as compared to tumors with low CcO activity. SOC consists of post-surgical radiation therapy with concurrent Temozolomide followed by up to 12 cycles of adjuvant Temozolomide.
Additional outcomes are to study the relation between CcO activity in the GBM tumors and progression free survival times (PFS; time intervals from dates of diagnosis to documented disease progression by MRI or tumor-related death) and, to compare the prognostic abilities of CcO activity to other frequently used biomarkers, namely the methylation status of O6-methylguanine-DNA methyltransferase (MGMT), on OS and PFS.
Tumor tissue will be submitted by participating centers for measurements of the CcO/Citrate Synthase (CS), MGMT promoter methylation. The subjects will agree to receive the SOC treatment. The therapeutic option at the time of first recurrence is at the discretion of the treating physician. PFS and OS times will be compared with high vs. low CcO activity and with the MGMT methylation status of the tumor. At the time of death or at 24 months s/p enrollment (whichever comes first), the site PI will complete an exit form documenting the details of enrollees' treatment history and date(s) of any tumor progression.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 153
Not provided
Exclusion criteria are proposed that will exclude subjects with pre-existing co-morbidities that could contribute to pre-mature death (e.g., significant cardiovascular history), with non-included pretreated tumors occupying either intracranial and extra-axial space, significantly impaired neurological performance status (e.g., KPS>60), with glial tumors that are genomically distinct from primary GBM tumors (e.g., gliomas arising from a previously diagnosed lower grade than GBM) or those unable to complete the fundamental requirements of the study.
- Inability to fulfill the requirements of the protocol
- Secondary GBM or other gliomas.
- History of sensitivity to Temozolomide.
- Planned upfront treatment with any anti-angiogenic agent targeting the (vascular endothelial growth factor (VEGF) pathway including but not limited to bevacizumab, cediranib, vandetanib, sunitinib, pazopanib, aflibercept, or sorafenib or any immunotherapy regimen.
- Any severe post-operative infection or other complications that may significantly delay the initiation of brain tumor therapy, or other conditions that, in the opinion of the investigator, would compromise the subject's ability to participate in the study.
Note: Use of Gliadel wafers, in combination with surgical resection, is allowed if the patient is to follow standard-of-care treatment post-operatively (i.e., radiation therapy with temozolomide). Use of Gliadel wafers during surgery with only radiation therapy post-operatively is excluded (i.e., omitting temozolomide).
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Overall Survival (OS) Date of diagnosis through 24 months after enrollment This biomarker trial is designed to prospectively evaluate the hypothesis that the overall survival (OS) time of a subject with newly diagnosed primary GBM tumors, treated by standard of care (SOC), is a function of the CcO enzymatic activity in the tumor. OS is defined as the time interval from date of first diagnosis to death from any cause, irrespective of post-SOC therapies, assessed up to 24 months from accrual.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (19)
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Swedish Neuroscience Institute
🇺🇸Seattle, Washington, United States
University of Miami
🇺🇸Miami, Florida, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
SUNY Stony Brook
🇺🇸Stony Brook, New York, United States
University of Texas Southwestern
🇺🇸Dallas, Texas, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
UC Davis
🇺🇸Sacramento, California, United States
Washington University Medical School
🇺🇸Saint Louis, Missouri, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Vanderbilt University
🇺🇸Nashville, Tennessee, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States