Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Cytochrome C Oxidase Activity in Newly Diagnosed Glioblastoma Multiforme (GBM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02997423
Recruitment Status : Active, not recruiting
First Posted : December 20, 2016
Last Update Posted : March 20, 2019
Sponsor:
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
NeuroNEXT Network
Information provided by (Responsible Party):
Corinne Griguer, 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.

Condition or disease
Glioblastoma

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.


Layout table for study information
Study Type : Observational
Actual Enrollment : 153 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Prospective Phase II Study of Cytochrome C Oxidase Activity as a Novel Biomarker In Subjects With Newly Diagnosed Primary Glioblastoma Multiforme
Actual Study Start Date : November 30, 2016
Estimated Primary Completion Date : November 30, 2020
Estimated Study Completion Date : November 30, 2022

Resource links provided by the National Library of Medicine





Primary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: 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.


Other Outcome Measures:
  1. Progression Free Survival (PFS) [ Time Frame: Date of diagnosis through 48 months after enrollment ]
    This biomarker trial is designed to prospectively evaluate the hypothesis that progression free survival time (PFS) is a function of the CcO enzymatic activity in the tumor. PFS is defined as time interval from date of surgery to first documented progression according to the RANO criteria, irrespective of post-SOC therapies.

  2. MGMT methylation status on OS and PFS [ Time Frame: Date of diagnosis through 24 months after enrollment ]
    Compare the prognostic abilities of CcO activity to another frequently used biomarker, the methylation status of O6-methylguanine-DNA methyltransferase (MGMT) on OS and PFS times.


Biospecimen Retention:   Samples With DNA
Tumor tissue and DNA


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Newly diagnosed primary Glioblastoma multiforme (GBM) patients who will receive standard of care treatment.
Criteria

Inclusion Criteria

  1. Willingness and ability to provide written informed consent and to comply with the study protocol as judged by Physician interview (NOTE: This could be patient's Neurosurgeon, Neuro-Oncologist or Study Investigator). If patient lacks capacity to consent, a legally authorized representative is allowed to provide written informed consent.
  2. Age ≥ 21 years
  3. Karnofsky Performance Status (KPS) ≥ 60.
  4. Subjects' planned upfront treatment to be standard of care treatment with radiotherapy and temozolomide (i.e. TEMODAR) for histologically confirmed GBM at initial diagnosis
  5. No history of other malignancies except adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, or other curatively treated solid tumors with no evidence of disease for at least 5 years.
  6. No serious active infection (e.g., wound infection requiring parenteral antibiotics) or other serious underlying medical conditions that in the opinion of the investigator would compromise standard of care treatment.
  7. No other condition (e.g., psychological or geographical) that would preclude study compliance.
  8. An MRI that is consistent with a primary malignant glioma
  9. Histologically confirmed newly diagnosed primary GBM before treatment using World Health Organization (WHO) classification criteria (A local pathology report constitutes adequate documentation of histology for initial study enrollment, however central pathology review will be required to confirm the diagnosis of GBM for final data analysis).
  10. Viability of tumor tissue representative of GBM ≥ 70 mg, snap-frozen within 30 minutes of resection, 10 minutes or less at room temperature.
  11. All subjects must have received maximal safe resection followed by standard radiation therapy with concomitant Temozolomide taken during the course of radiation therapy.

Exclusion Criteria:

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.

  1. Inability to fulfill the requirements of the protocol
  2. Secondary GBM or other gliomas.
  3. History of sensitivity to Temozolomide.
  4. 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.
  5. 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).


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02997423


Locations
Layout table for location information
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
UC Davis
Sacramento, California, United States, 95817
United States, Florida
University of Miami
Miami, Florida, United States, 33136
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60208
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Missouri
Washington University Medical School
Saint Louis, Missouri, United States, 63110
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467
Columbia University Medical Center
New York, New York, United States, 10032
University of Rochester Medical Center
Rochester, New York, United States, 14642
SUNY Stony Brook
Stony Brook, New York, United States, 11794
United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45219
Ohio State University
Columbus, Ohio, United States, 43210
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15261
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37235
United States, Texas
University of Texas Southwestern
Dallas, Texas, United States, 75390
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84112
United States, Washington
Swedish Neuroscience Institute
Seattle, Washington, United States, 98122
Sponsors and Collaborators
Corinne Griguer
National Institute of Neurological Disorders and Stroke (NINDS)
NeuroNEXT Network
Investigators
Layout table for investigator information
Principal Investigator: Corinne E Griguer, PhD University of Iowa

Publications:
Layout table for additonal information
Responsible Party: Corinne Griguer, Associate Professor, University of Iowa
ClinicalTrials.gov Identifier: NCT02997423     History of Changes
Other Study ID Numbers: NN106
U01NS093663 ( U.S. NIH Grant/Contract )
First Posted: December 20, 2016    Key Record Dates
Last Update Posted: March 20, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

The requestor must submit a formal written request for data sharing, and the request must be approved by the NeuroNEXT Steering Committee and the Publication Committee before any data are shared. Prior to data sharing, the DCC and the external source must also execute a data sharing agreement that includes a description of the data that are requested and how the data will be shared. A contract / usage agreement may be required.

The DCC will submit de-identified datasets and associated documentation to NINDS for archiving and public access, consistent with the current NINDS Data Sharing policy. The DCC will provide documentation with each final dataset to ensure that other users can efficiently and accurately use the dataset, and to prevent misinterpretation or misuse. This documentation may include information about how the data were collected, provide details about the code used to generate the dataset, and define variables and variable field locations.

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Analytic Code
Time Frame: Upon request.
Access Criteria: Written request to principal investigator.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Corinne Griguer, University of Iowa:
Glioblastoma Multiforme
Biomarker
Cytochrome C Oxidase
Newly diagnosed
Additional relevant MeSH terms:
Layout table for MeSH terms
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue