NN106

Principal Investigator: Howard Colman
Keywords: brain tumor Department: Neurosurgery - Adult
IRB Number: 00093191 Co Investigator: Randy Jensen
Specialty: Neurosurgery, Neurosurgery
Sub Specialties: Neuro-Oncology, Brain Tumors
Recruitment Status: Not yet recruiting

Contact Information

Cathy Revere
cathy.revere@hsc.utah.edu
801-585-9516

Brief Summary

Primary Objective

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, defined as CcO/citrate synthase (CcO/CS) ratio > 4, are associated with shorter OS time as compared to tumors with low CcO activity (CcO/CS < 4).  SOC consists of post-surgical radiation therapy with concurrent Temozolomide followed by up to 12 cycles of adjuvant Temozolomide.  

Secondary Objectives

 

1.  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,

2.  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. 

 

Inclusion Criteria

 

Inclusion Criteria:

Subject Characteristics:

  1. Willingness to undergo a maximal debulking surgery and radiotherapy concomitant with temozolomide at initial diagnosis
  2. Willingness and ability to provide written informed consent and to comply with the study protocol as judged by the investigator.
  3. Age ≥ 21 years.
  4. KPS score ≥ 60.
  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 would preclude study treatment
  7. No other condition (e.g., psychological or geographical) that would preclude study compliance

 

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. Any serious disease or condition 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 Temodar.
  5. Planned upfront treatment with any anti-angiogenic agent targeting the 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.