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

Sponsor

Corinne Griguer (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02997423

Collaborator

National Institute of Neurological Disorders and Stroke (NINDS) (NIH), NeuroNEXT Network (Other)

153

Enrollment

Locations

Anticipated Duration (Months)

8.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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	Intervention/Treatment	Phase
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.

Study Design

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 :

Nov 30, 2016

Anticipated Primary Completion Date :

Nov 30, 2022

Anticipated Study Completion Date :

Nov 30, 2024

Outcome Measures

Primary Outcome Measures

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.

Other Outcome Measures

Progression Free Survival (PFS) [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.
MGMT methylation status on OS and PFS [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

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.
Age ≥ 21 years
Karnofsky Performance Status (KPS) ≥ 60.
Subjects' planned upfront treatment to be standard of care treatment with radiotherapy and temozolomide (i.e. TEMODAR) for histologically confirmed GBM at initial diagnosis
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.
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.
No other condition (e.g., psychological or geographical) that would preclude study compliance.
An MRI that is consistent with a primary malignant glioma
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).
Viability of tumor tissue representative of GBM ≥ 70 mg, snap-frozen within 30 minutes of resection, 10 minutes or less at room temperature.
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.

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	UC Davis	Sacramento	California	United States	95817
3	University of Miami	Miami	Florida	United States	33136
4	Northwestern University	Chicago	Illinois	United States	60208
5	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
6	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
7	Washington University Medical School	Saint Louis	Missouri	United States	63110
8	Montefiore Medical Center	Bronx	New York	United States	10467
9	Columbia University Medical Center	New York	New York	United States	10032
10	University of Rochester Medical Center	Rochester	New York	United States	14642
11	SUNY Stony Brook	Stony Brook	New York	United States	11794
12	University of Cincinnati	Cincinnati	Ohio	United States	45219
13	Ohio State University	Columbus	Ohio	United States	43210
14	Oregon Health & Science University	Portland	Oregon	United States	97239
15	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15261
16	Vanderbilt University	Nashville	Tennessee	United States	37235
17	University of Texas Southwestern	Dallas	Texas	United States	75390
18	University of Utah	Salt Lake City	Utah	United States	84112
19	Swedish Neuroscience Institute	Seattle	Washington	United States	98122

Sponsors and Collaborators

Corinne Griguer
National Institute of Neurological Disorders and Stroke (NINDS)
NeuroNEXT Network

Investigators

Principal Investigator: Corinne E Griguer, PhD, University of Iowa

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Corinne Griguer, Associate Professor, University of Iowa

ClinicalTrials.gov Identifier:

NCT02997423

Other Study ID Numbers:

NN106
U01NS093663

First Posted:

Dec 20, 2016

Last Update Posted:

Mar 8, 2022

Last Verified:

Mar 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Corinne Griguer, Associate Professor, University of Iowa

Glioblastoma Multiforme

Biomarker

Cytochrome C Oxidase

Newly diagnosed

Additional relevant MeSH terms:

Glioblastoma

Study Results

No Results Posted as of Mar 8, 2022