The primary objective of this trial is to evaluate overall survival of patients with
O[6]-methylguanine-DNA methyltransferase (MGMT) methylated glioblastoma treated with or
without six months of adjuvant TMZ after standard radiation (6000 centigray (cGy)) plus
concurrent Temozolomide (TMZ).
Secondary Objectives include to prospectively assess the overall adverse event profile in the
two treatment arms. To compare lymphocyte counts overtime between the two treatment arms and
to prospectively compare quality of life in the two treatment arms as assessed by MD Anderson
Symptom Inventory-Brain Tumor Module (MDASI-BT) and Neurological quality of Life/minimal
infecting dose (NeuroQoL) (MID). The study will also compare progression-free survival
between the two treatment arms.
Recent phase III trials in patients with newly diagnosed patients with glioblastoma have
demonstrated that adding new agents (such as cilengitide, bevacizumab, or nivolumab) to
standard radiation and TMZ do not improve survival in this disease. The modest effects on
survival observed with the Optune® device are offset by the high costs, inconvenience, and
impact on the social interactions of patients wearing this device. Unfortunately, there are
currently no novel therapies poised to displace the European Organization Research &
Treatment Cancer (EORTC) regimen as the standard of care for patients with newly diagnosed
Glioblastoma Multiforme (GBM).As a result, a formal evaluation of the efficacy of the 6
months of adjuvant TMZ in this regimen is important to patients and research studies.
This is of particular importance in the 40% of patients who have MGMT methylated
glioblastoma. The very small benefit observed in MGMT unmethylated patients has led
investigators in Europe and the United States of America (including Cancer Therapy Evaluation
Program (CTEP) sponsored studies) to approve clinical trials in MGMT unmethylated patients
with newly diagnosed glioblastoma that entirely omit TMZ in both the concurrent and the
adjuvant settings Given the marginal value of TMZ in the MGMT unmethylated patient
population, the investigator's propose to study the value of adjuvant TMZ in the subset of
the MGMT methylated population. If omitting adjuvant TMZ is not detrimental to outcomes in
the methylated population then it is extremely unlikely to benefit the unmethylated
population where TMZ has even less effect.
Therefore, exploring the value of the six months of adjuvant TMZ in patients with newly
diagnosed MGMT methylated glioblastoma is important. If this was shown to be of minimal value
in prolonging survival there would be an immediate impact on both the standard care of
patients and research efforts to improve therapeutic outcomes.
Inclusion Criteria:
1. Patients must be 18 years of age or older.
2. Patients must have a Karnofsky Performance Status ≥ 60% (i.e. the patient must be able
to care for himself/herself with occasional help from others).
3. Patients must have had a pathologically confirmed recently diagnosed primary
glioblastoma before they began concurrent radiation and temozolomide.
4. Patients must have tumor MGMT methylation status of methylated using a Clinical
Laboratory Improvement Amendments (CLIA)-approved diagnostic test. Results of
routinely-used methods for MGMT methylation testing (e.g. Mutagenically separated-
polymerase chain reaction (MS-PCR) or quantitative PCR) are acceptable.
5. Documented mutated isocitrate dehydrogenase 1 gene (IDH1) isocitrate dehydrogenase 1
gene (IDH2)status: patients with either wild-type or(IDH) status are eligible.
Patients with no documented status are also eligible and the status should be listed
as unknown.
6. Patients must be completing or have completed 6 weeks of standard concurrent RT/TMZ.
7. Patients' post-operative treatment must have included at least 80% of standard
radiation and concomitant temozolomide. Patients may not have received any other prior
chemotherapy, immunotherapy or therapy with biologic agent (including immunotoxins,
immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins,
tumor-infiltrating lymphocytes (TIL), lymphokine activated killer cells (LAK) or gene
therapy), or hormonal therapy for their brain tumor. Prior Gliadel Wafers are allowed.
Glucocorticoid therapy is allowed.
8. Patients must be clinically eligible for the six months of adjuvant temozolomide.
9. Patients must be able to provide written informed consent.
10. Patients must have baseline MRI performed within the 21 days prior to starting
entering the "adjuvant" treatment or observation period.
11. Patients must have the following organ and marrow functions:
Absolute neutrophil count ≥1,500/µL Platelets ≥100,000/µL Hemoglobin ≥ 9 g/dL Total
bilirubin ≤1.5 × institutional upper limit of normal (ULN), (except for patients with known
Gilbert's syndrome who must have normal direct bilirubin) aspartate aminotransferase (AST)
serum glutamic-oxaloacetic transaminase (SGOT)/ alanine transaminase (ALT) serum
glutamic-pyruvic transaminase (SGPT) ≤ 2.5 × ULN Creatinine ≤1.5 × ULN OR Creatinine
clearance ≥ 60 mL/min/1.73m2
Exclusion Criteria:
1. Patients receiving any other standard or investigational agents or who plan to use the
OPTUNE device or other therapies for the glioblastoma are ineligible.
2. Patients with uncontrolled intercurrent illness including, but not limited to, ongoing
or active infection or psychiatric illness/social situations that would limit
compliance with study requirements, are ineligible.
3. Patients must not have received prior RT, chemotherapy (except for their concurrent
radiation and temozolomide for their recently diagnosed glioblastoma), immunotherapy
or therapy with a biologic agent (including immunotoxins, immunoconjugates, antisense,
peptide receptor antagonists, interferons, interleukins, tumor-infiltrating
lymphocytes, lymphokine-activated killer cells, or gene therapy), or hormonal therapy
for their brain tumor. Corticosteroid therapy is allowed.
4. Patients must not have had a prior diagnosis of a lower grade glioma.
5. No active treatment for other cancers in the past 3 years.
