An Investigation of Brain Tumor Metabolism in Patients Undergoing Surgical Resection
The study is designed to use infusion of a non-radioactive, naturally occurring isotope of glucose (13C) in patients undergoing surgical resection for a newly identified brain mass to obtain the metabolic phenotype of the tumor, and correlate it with the histopathological diagnosis. In each patient, 13C NMR spectral analysis of tumor extracts will be obtained after intraoperative infusion of [U-13C]glucose or [1,2-13C]glucose. Whenever feasible, patients will undergo 3 preoperative imaging studies - 18FDG-PET, diffusion tensor imaging with 1H-spectroscopy on 3T MR scanner, and ultra high resolution MR imaging on the 7T MR scanner. The results of these imaging studies will be correlated with the metabolic phenotype to generate a comprehensive non-invasive view of the tumor with the goal of identifying infiltrative, metabolically active tumor cells within the brain. In addition, a comprehensive molecular profile of the tumor will be obtained and enable a genotype-metabolic phenotype comparative analysis.
Correlative Translational Research The investigators will obtain tumor tissue from each patient for comprehensive molecular analysis (array CGH, expression profiling, methylation profiling) which will be correlated with tumor histology, the metabolites identified by 1H-MR spectroscopy and the 13Cglucose metabolic profile. Patients will be followed at designated time points along their treatment course to obtain information about ongoing treatment and response, time to tumor progression and overall survival. These parameters will be used in correlational analysis with the metabolic phenotype.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
|Official Title:||An Investigation of Brain Tumor Metabolism in Patients Undergoing Surgical Resection|
- metabolic phenotype correlation to clinical endpoints [ Time Frame: at end of follow-up period- between days 1-14 ] [ Designated as safety issue: No ]To correlate the metabolic phenotype obtained from histopathological diagnosis with the clinical endpoints of time to tumor progression and overall survival during the 5 years of patient follow-up
- baseline imaging data review [ Time Frame: at time of study entry- within 14 days of surgery ] [ Designated as safety issue: No ]To compare and contrast baseline imaging data obtained on the 7T MR among the major brain tumor histological subtypes (e.g. low grade gliomas, glioblastoma, brain metastases) with emphasis on the differences in vascular integrity and extent of tumor infiltration for each subtype
- molecular profiling [ Time Frame: after surgical resection- day 0 ] [ Designated as safety issue: No ]To correlate changes on 7T with the molecular profile of the primary resected tumor (molecular profiling is being done under a separate IRB approved protocol).
|Study Start Date:||May 2010|
|Estimated Study Completion Date:||July 2015|
|Estimated Primary Completion Date:||July 2015 (Final data collection date for primary outcome measure)|
Procedure: surgical resection of a brain tumor
This study has been expanded to include subjects with primary tumors outside the central nervous system, including breast cancer, lung cancer, melanoma, renal cell carcinoma, prostate cancer and colon cancer. Patients with a brain mass identified on brain imaging and who need surgical resection of the mass will be eligible for this metabolism study. Eligible study patients will be screened, recruited, and enrolled at UT Southwestern Medical Center in the Harold C. Simmons Comprehensive Cancer Center, University Hospital - Zale Lipshy and University Hospital - St. Paul, Children's Medical Center of Dallas as well as at Parkland Health and Hospital System. We will consent 60 patients, including projected screen failures and early withdrawals, and anticipate that we will study 25 patients in this clinical protocol. Once enrolled, patients will undergo a series of preoperative brain imaging studies including 3T MRI with Diffusion Tensor Imaging (DTI) and 1H-MR spectroscopy, 7T MRI and a brain 18FDG-PET scan within 7-14 days of the scheduled operation. Of these studies, only the 3T MRI is standard of care. The DTI and 1H-MR spectroscopy are additional scanning sequences that are being done for research purposes. Similarly, the 7T MRI and the 18FDG-PET are being done for research purposes only. On the day of surgery, the patient will have a peripheral IV started while waiting in the preoperative holding area and a 20% solution of either [U-13C]glucose and/or [1,2-13C]acetate (to be determined for each individual patient by the PI) will be infused at a rate of 4g/hr for a maximum of 4 hours. During the infusion period, 4 timed blood samples will be collected for NMR analysis of 13C-glucose in the blood. The infusion will continue until the tumor has been resected and samples have been collected and flash frozen for 13C-NMR spectral analysis and molecular analyses. The infusion and tumor collection for 13C-NMR analysis is being done for research purposes only. However, the remainder of the neurosurgical operative and post-operative procedures will be followed according to standard practice. The patient will be seen 10-14 days after surgery for a follow up visit at which time an assessment of adverse events will be performed. Thereafter, every 6 months for 5 years or until death, the patient will be contacted and data regarding treatment, responses, and tumor progression will be collected for correlative analysis.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01668082
|Contact: Sarah McNeil, RNfirstname.lastname@example.org|
|United States, Texas|
|University of Texas Southwestern||Recruiting|
|Dallas, Texas, United States, 75390|
|Contact: Sarah McNeil, RN 214-648-5573 email@example.com|
|Sub-Investigator: Craig Malloy, MD|
|Sub-Investigator: Changho Choi, PhD|
|Sub-Investigator: Bruce Mickey, MD|
|Sub-Investigator: Christopher Madden, MD|
|Sub-Investigator: Robert Bachoo, MD, PhD|
|Sub-Investigator: Ralph Deberardinis, MD, PhD|
|Sub-Investigator: Juan Pascual, MD, PhD|
|Sub-Investigator: Kimmo Hatanpaa, MD, PhD|
|Sub-Investigator: Jack Raisanen, MD|
|Principal Investigator:||Elizabeth Maher, MD, PhD||University of Texas|