An Investigation of Brain Tumor Metabolism in Patients Undergoing Surgical Resection

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by University of Texas Southwestern Medical Center
Sponsor:
Information provided by (Responsible Party):
University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:
NCT01668082
First received: June 12, 2012
Last updated: September 12, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention
Brain Mass
Procedure: surgical resection of a brain tumor

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of Texas Southwestern Medical Center:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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).


Estimated Enrollment: 40
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)
Arms Assigned Interventions
Experimental: surgical resection of a brain tumor

The patient will undergo surgical removal of the tumor after infusion of 13C-glucose using standard neurosurgical technique, including frameless stereotaxy for surgical navigation, and microsurgical technique.

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Procedure: surgical resection of a brain tumor
The patient will undergo surgical removal of the tumor after infusion of 13C-glucose using standard neurosurgical technique, including frameless stereotaxy for surgical navigation, and microsurgical technique.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female, age 18 years or older of any racial or ethnic group
  • Spanish-speaking patients will be eligible
  • Pre-operative brain MR imaging suggestive of a brain tumor
  • Patient able and willing to provide informed consent
  • Karnofsky Performance status > 70%
  • Negative serum pregnancy test or child bearing potential terminated by surgery, radiation, menopause or current use of two approved methods of birth control

Exclusion Criteria:

  • Patient unable to provide informed consent
  • Karnofsky Performance status < 70%
  • Patients who are claustrophobic or have other contraindications to MRI, such as implanted pacemaker device vascular clips, surgical clips, prosthetic valves, pacemakers, otologic implants
  • NYHA class III and IV congestive heart failure
  • Psychiatric or addictive disorders that preclude obtaining informed consent
  • Unstable angina
  • Pregnant or lactating women
  • Women of childbearing potential who refuse a pregnancy test (performed during screening)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01668082

Contacts
Contact: Sarah McNeil, RN 214-648-5573 sarah.mcneil@utsouthwestern.edu

Locations
United States, Texas
University of Texas Southwestern Recruiting
Dallas, Texas, United States, 75390
Contact: Sarah McNeil, RN    214-648-5573    sarah.mcneil@utsouthwestern.edu   
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         
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Investigators
Principal Investigator: Elizabeth Maher, MD, PhD University of Texas
  More Information

No publications provided

Responsible Party: University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT01668082     History of Changes
Other Study ID Numbers: 062010-157
Study First Received: June 12, 2012
Last Updated: September 12, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Texas Southwestern Medical Center:
Patients with newly identified brain mass

ClinicalTrials.gov processed this record on October 19, 2014