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

Summary

This is a prospective, randomized, placebo-controlled, multi-center study of patients with newly diagnosed glioblastoma to evaluate a peptide vaccine (SurVaxM) in emulsion with Montanide given together with locally administered sargramostim plus adjuvant oral temozolomide (Arm A) versus saline-Montanide emulsion with locally administered saline (instead of sargramostim) plus adjuvant oral temozolomide (Arm B).

SurVaxM contains a synthetic peptide conjugate that stimulates immune responses capable of killing cancer cells that express the survivin molecule.

Inclusion Criteria
  1. Age ≥ 18 years of age.
  2. Have a Karnofsky performance status ≥ 70.
  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:
    1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
    2. Platelets ≥ 100 x 109/L
    3. Hemoglobin (Hgb) ≥ 9.0 g/dL
    4. Total bilirubin: ≤ 1.5 x ULN
    5. ALT and AST ≤ 4.0 x ULN
    6. Creatinine ≤ 1.8 mg/dL
    7. Prothrombin time (PT) within 1.5x normal limits
    8. Activated partial thromboplastin time (aPPT) within 1.5x control
    9. International Normalized Ration (INR) less than or equal to 1.5x control.
  7. Patient 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 that was completed within 72 hours after 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).
  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 6-week course of RT and completed ≥ 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 timepoints based on changes in: neurologic exam, corticosteroid use or radiographic progression (i.e., baseline MRI evaluation).
  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 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.
  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 prior to receiving any study related procedure.
Exclusion Criteria
  1. Recurrent or progressive glioblastoma
  2. Gliosarcoma, anapestic 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 of 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 in this trial.
  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 o the patient to receive the treatment 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 radiation therapy and temozolomide treatment (i.e., chemoradiation).
  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. Know 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 any other 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.
Investigator(s)

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