A Randomized Phase 3 Open Label Study of Nivolumab vs Temozolomide Each in Combination with Radiation Therapy in Newly Diagnosed Adult Subjects with Unmethylated MGMT (tumor O-6-methylguanine DNA methyltransferase) Glioblastoma

Study ID
STU 012016-083

Study Sites

  • Clements University Hospital

Rafael Leon

Principal Investigator
Edward Pan, M.D.


Study Design:

This study will enroll subjects with newly-diagnosed glioblastoma (GBM), following surgical resection of the
tumor. after informed consent is obtained, subjects will enter the screening phase. Tumor tissue will be evaluated
for MGMT methylation by a central laboratory assay. in order to randomize 550 eligible subjects, a total of
approximately 1200 subjects are expected to have tumor screening, of which approximately 600 subjects are
anticipated to have unmethylated MGMT tumors.
Post-operative baseline MRi preferably following consensus recommendations, must be obtained prior to randomization. it is strongly recommended that this scan be obtained [Less Than] 72 hrs or [Greater Than]14 days post-surgery in order to minimize artifact. There is no requirement that this baseline scan be performed on a [Quote]qualified[Quote] machine (a qualified MRi is one that meets the imaging Manual specifications and has been validated with the required phantom scan). if a post-operative MRi is not available, a high-quality, contrast-enhanced CT scan may be performed initially, but in this case a contrast-enhanced MRi must be performed prior to randomization ([Greater Than] 2 weeks post-op preferred).
Subjects with a central laboratory result of unmethylated MGMT may continue in the screening phase, in which
eligibility for randomization will be documented and baseline demographic and disease information submitted; for
When ready to begin study treatment, subjects will proceed to the treatment phase of the study. all subjects who
enter the treatment phase, ie, all randomized subjects, will be followed for safety and tolerability, tumor progression
and survival. a contrast-enhanced MRi should be performed 4 weeks ((+-) 7 days) after completing radiation therapy, then every
8 weeks ((+-)7 days) until progression regardless of treatment schedule or dose delays.. Tumor progression will be assessed using
Radiologic assessment in neuro-oncology criteria (Rano). additional assessments will be performed for
cognitive function, neurologic function, biomarkers, and patient-reported quality of life outcomes.
after cessation of study treatment for any reason, all randomized subjects will enter a follow up phase. in the shortterm,
visits are defined for reporting of treatment-related adverse events. all subjects in whom disease progression
had not been detected at the time study treatment is stopped will be followed closely for progression with contrast enhanced MRi every 8 weeks ((+-) 7 days) until progression. after progression subsequent treatment will be reported. all randomized
subjects MuST be followed for survival (primary endpoint).

Participant Eligibility

Key Inclusion criteria:

* Males and Females age >= 18 years old;

* Newly diagnosed histologically confirmed supratentorial glioblastoma (Grade 4 malignant glioma by World
Health Organization including gliosarcoma)
o No treatment for GBM other than surgery;
o Post-operative baseline MRI, preferably following consensus recommendations,
must be obtained prior to randomization. It is strongly recommended that this scan be
obtained <72 hrs or >14 days post-surgery in order to minimize artifact;

* Substantial recovery from surgical resection
o No major ongoing safety issues following surgery
o Able to taper steroids (preferably discontinued). Dose at randomization must be <= 20 mg prednisone daily
or <= 3 mg dexamethasone daily (or equivalent)

* Centrally confirmed tumor unmethylated MGMT

* Karnofsky performance status of >=70

* Clinically appropriate for concomitant temozolomide plus radiation therapy based on investigator judgement.