Purpose

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

Eligibility

Eligible Ages
Over 21 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

Pre-Surgery:

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).

2. Age ≥ 21years

3. Karnofsky Performance Status (KPS) ≥ 60.

4. Subjects' planned upfront treatment to be SOC 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

Post-Surgery:

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. Availability 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. 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.
  3. Secondary GBM or other gliomas.
  4. History of sensitivity to Temozolomide.
  5. 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.
  6. GLIADEL wafers in combination with surgical resection.

Study Design

Phase
Study Type
Observational
Observational Model
Other
Time Perspective
Prospective

Recruiting Locations

Montefiore Medical Center
Bronx, New York
Contact:
Fatema Malbari
718-920-4378
fmalbari@montefiore.org

More Details

NCT ID
NCT02997423
Status
Recruiting
Sponsor
University of Alabama at Birmingham

Study Contact

Corinne E Griguer, PhD
205-934-8297
cegriguer@uabmc.edu

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.