Prospective Randomized Placebo-Controlled Trial of SurVaxM Plus Adjuvant Temozolomide for Newly Diagnosed Glioblastoma (SURVIVE)

∙ To be included in this study, participants must meet the following criteria:

• Age ≥ 18 years of age.

• Have a Karnofsky performance status ≥ 70 (i.e., the patient must be able to care for him/herself with occasional help from others; refer to Appendix A).

• Pathologically confirmed diagnosis of glioblastoma of the cerebrum.

• The result of tumor MGMT methylation study must be available.

• The result of tumor IDH-1 mutation test must be available.

• Have the following clinical laboratory values obtained within 14 days prior to registration:

• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L

• Platelets ≥ 100 x 109/L

• Hemoglobin (Hgb) ≥ 9.0 g/dL

• Total bilirubin: ≤ 1.5 x ULN

• ALT and AST ≤ 4.0 x ULN

• Creatinine ≤ 1.8 mg/dL

• Prothrombin time (PT) within 1.5x normal limits

• Activated partial thromboplastin time (aPPT) within 1.5x control

• International Normalized Ration (INR) less than or equal to 1.5x control

‣ Patient must have no active bleeding or pathological condition that carries a high risk of bleeding (e.g., coagulopathy)

‣ Available results from a contrast-enhanced, post-operative brain MRI that was completed within 72 hours after surgery documenting either:

∙ a. gross total resection consisting of no gadolinium enhancement; or b. near-total resection consisting of either ≤ 1 cm3 nodular (i.e. volumetric) enhancement or ≤ 100 mm2 in cross sectional area (i.e. linear enhancement). Note: Patients who undergo either stereotactic biopsy or open biopsy for tissue diagnosis, or partial tumor resection, and who subsequently have a definitive surgical resection may still be eligible for inclusion, provided that randomization can occur within 16 weeks of the date of surgical resection. To be eligible, such patients must still meet postoperative imaging entry criteria as defined in item #8 above.

• Patients must have completed initial radiation therapy with TMZ (chemoradiation) according to established Stupp protocol (Stupp, 2005) for the treatment of their glioblastoma (i.e., completed 6-week course of RT and completed ≥ 75% of a course of concurrent TMZ chemotherapy).

⁃ Patients must be randomized within 16 weeks of surgical resection of their newly diagnosed glioblastoma.

⁃ No evidence of progressive disease at the post-chemoradiation timepoint based on changes in: neurologic exam, corticosteroid use or radiographic progression (i.e., baseline MRI evaluation). (See Section 14.5 for suspected pseudo-progression.)

⁃ Participants of child-bearing potential (not surgically sterile or postmenopausal) must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry and have a negative pregnancy test prior to starting study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

⁃ Dexamethasone dose less than or equal to 4 mg daily at time of study enrollment. Every reasonable effort should be made to reduce the dose of corticosteroids to the absolute minimum dose required to control neurologic symptoms prior to receiving SurVaxM.

⁃ Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure.