IRB Study Number 21-1248
Phase Phase 2
Institute Taussig Cancer Institute
4.1 Primary Objective
• To compare overall survival (OS) in patients with newly diagnosed glioblastoma between treatment arms A and B.
4.2 Secondary Objectives
• To tabulate the number and type of grade 3 and grade 4 toxicities, according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAEs) Version 5.
• To compare progression free survival in patients with newly diagnosed glioblastoma between treatment Arms A and B,
• To compare treatment-associated overall survival at pre-specified time points (OS-15, OS-18 and OS-24) between treatment Arms A and B.
• To compare treatment-associated progression-free survival at pre-specified time points (PFS-3, PFS-6 and PFS-12) between treatment arms A and B.
4.3 Exploratory and Scientific Objectives
• To evaluate the predictive value of perfusion-weighted imaging in assessing pseudo-progression and post-vaccination enhancement in patients receiving SurVaxM
• To evaluate the objective image-based tumor response rate (applicable only for patients with evaluable disease at study entry as defined by RANO criteria).
• To evaluate molecular predictors of response to SurVaxM, including MGMT methylation status, anti-survivin immunoglobin titers, survivin-specific CD8+ responses, tumor survivin expression levels and other molecular tumor tissue markers.
1 Age ≥ 18 years of age.
2 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).
3 Pathologically confirmed diagnosis of glioblastoma of the cerebrum.
4 The result of tumor MGMT methylation study must be available.
5 The result of tumor IDH-1 mutation test must be available.
6 Have the following clinical laboratory values obtained within 14 days prior to registration:
o Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
o Platelets≥ 100 x 109/L
o Hemoglobin (Hgb) > 9.0 g/dL
o Total bilirubin: ≤ 1.5 x ULN
o ALT and AST ≤ 4.0 x ULN
o Creatinine ≤ 1.8 mg/dL
o Prothrombin time (PT) within 1.5x normal limits
o Activated partial thromboplastin time (aPPT) within 1.5x control
o International Normalized Ration (INR) less than or equal to 1.4x control
7 Patients must have no active bleeding or pathological condition that carries a high risk of bleeding (e.g., coagulopathy)
8 Available results from a contrast-enhanced, post-operative Brain MRI completed within 72 hours following surgery documenting either: 1) gross total resection consisting of no gadolinium enhancement; or 2) 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 the second procedure is performed within 14 days of the initial procedure and randomization can occur within 16 weeks of the date of surgical resection. In addition, to be eligible such patients must still meet post-operative imaging entry criteria as defined in item #8 above.
9 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 a full course of fractionated radiation therapy and ≥ 75% of a course of concurrent TMZ chemotherapy).
10 Patients must be randomized within 16 weeks of surgical resection of their newly diagnosed glioblastoma.
11 No evidence of progressive disease at the post-chemoradiation timepoint (baseline evaluation), based on changes in the neurologic exam, corticosteroid use, or radiographic progression. See Section 14.5 for suspected pseudo-progression.
12 Participants of child-bearing potential (not surgically sterile or post-menopausal) 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.
13 Dexamethasone dose less than or equal to 4 mg daily at time of study enrollment. Every effort should be made to reduce the dose of corticosteroids to the absolute minimum dose required to control neurologic symptoms prior to receiving SurVaxM.
14 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.
1 Recurrent or progressive glioblastoma.
2 Gliosarcoma, anaplastic astrocytoma, oligodendroglioma, ependymoma, low grade glioma or any histology other than glioblastoma
3 Multicentric glioblastoma or glioblastoma involving the brainstem or cerebellum, or leptomeningeal or spinal extension present at diagnosis.
4 Residual contrast enhancement > 1 cm3 on post-operative scan obtained within 72 hours following surgery.
5 Absence of MRI obtained within 72 hours of craniotomy documenting ≤ 1 cm3 contrast-enhancing tumor.
6 Patients who elect to have Optune therapy (Tumor Treating Fields) are not eligible to participate.
7 Patient has had non-standard radiation therapy for glioblastoma (i.e., whole brain radiation therapy, gamma knife or LINAC stereotactic radiosurgery).
8 Prior or concurrent immunotherapy for brain tumor, including immune checkpoint inhibitors (pembrolizumab, nivolumab or ipilimumab) or other cancer vaccine therapy.
9 Prior or concurrent treatment with bevacizumab.
10 Patients with serious concurrent infection or medical illness, which in the treating physician’s opinion would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety.
11 History of tuberculosis or other granulomatous disease.
12 Patient is pregnant or breast-feeding.
13 Patient has received any other chemotherapeutic agent or investigational drug in addition to standard of care radiation therapy with concomitant temozolomide (chemoradiation per Stupp protocol).
14 Patient with concurrent or prior malignancy is ineligible unless he or she has had curatively treated carcinoma-in-situ or basal cell carcinoma of the skin.
15 Patients who have had repeat craniotomy for tumor therapy after receiving RT and TMZ treatment.
16 Patients who have had surgical implantation of carmustine (Gliadel) wafers are not eligible to participate in this study.
17 Known history of systemic autoimmune disorder.
18 Known human immunodeficiency virus (HIV) positivity or acquired immunodeficiency syndrome (AIDS) related illness or other serious medical illness.
19 Patient has a contraindication to MRI scans or to gadolinium contrast agent
20 Patient has a contraindication to temozolomide.
21 Patient is unwilling or unable to follow protocol requirements.
22 Patient has received an investigational treatment for the glioblastoma.
23 Any condition which in the Investigator’s opinion makes the candidate unsuitable to receive the study drug or protocol procedures.