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

NCT ID: NCT02997423

Last Updated: 2023-02-13

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 153 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-11-30
• Study Completion Date: 2022-11-30

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.

Conditions

Glioblastoma

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility 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

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).

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

NeuroNEXT Network

OTHER

Sponsor Role: collaborator

University of Iowa

OTHER

Sponsor Role: lead

Responsible Party

Corinne Griguer

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Corinne E Griguer, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Iowa

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

UC Davis

Sacramento, California, United States

University of Miami

Miami, Florida, United States

Northwestern University

Chicago, Illinois, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Washington University Medical School

St Louis, Missouri, United States

Columbia University Medical Center

New York, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

SUNY Stony Brook

Stony Brook, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

University of Cincinnati

Cincinnati, Ohio, United States

Ohio State University

Columbus, Ohio, United States

Oregon Health & Science University

Portland, Oregon, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Vanderbilt University

Nashville, Tennessee, United States

University of Texas Southwestern

Dallas, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Swedish Neuroscience Institute

Seattle, Washington, United States

Countries

United States

References

Vogelbaum MA, Jost S, Aghi MK, Heimberger AB, Sampson JH, Wen PY, Macdonald DR, Van den Bent MJ, Chang SM. Application of novel response/progression measures for surgically delivered therapies for gliomas: Response Assessment in Neuro-Oncology (RANO) Working Group. Neurosurgery. 2012 Jan;70(1):234-43; discussion 243-4. doi: 10.1227/NEU.0b013e318223f5a7.

Reference Type: BACKGROUND

PMID: 21593697 (View on PubMed)

Galanis E, Wu W, Cloughesy T, Lamborn K, Mann B, Wen PY, Reardon DA, Wick W, Macdonald D, Armstrong TS, Weller M, Vogelbaum M, Colman H, Sargent DJ, van den Bent MJ, Gilbert M, Chang S. Phase 2 trial design in neuro-oncology revisited: a report from the RANO group. Lancet Oncol. 2012 May;13(5):e196-204. doi: 10.1016/S1470-2045(11)70406-5.

Reference Type: BACKGROUND

PMID: 22554547 (View on PubMed)

Griguer CE, Oliva CR, Coffey CS, Cudkowicz ME, Conwit RA, Gudjonsdottir AL, Ecklund DJ, Fedler JK, Neill-Hudson TM, Nabors LB, Benge M, Hackney JR, Chase M, Leonard TP, Patel T, Colman H, de la Fuente M, Chaudhary R, Marder K, Kreisl T, Mohile N, Chheda MG, McNeill K, Kumthekar P, Dogan A, Drappatz J, Puduvalli V, Kowalska A, Graber J, Gerstner E, Clark S, Salacz M, Markert J. Prospective biomarker study in newly diagnosed glioblastoma: Cyto-C clinical trial. Neurooncol Adv. 2021 Dec 24;4(1):vdab186. doi: 10.1093/noajnl/vdab186. eCollection 2022 Jan-Dec.

Reference Type: RESULT

PMID: 35088051 (View on PubMed)

Other Identifiers

U01NS093663

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NN106

Identifier Type: -

Identifier Source: org_study_id