This phase II trial studies the side effects and how well vaccine therapy works when given together with temozolomide in treating patients with newly diagnosed glioblastoma. Vaccines made from the survivin peptide or antigen may help the body build an effective immune response to kill tumor cells that express survivin. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether temozolomide is more effective with or without vaccine therapy in treating glioblastoma.
PRIMARY OBJECTIVES: I. To evaluate 6-month progression-free survival (PFS6) in patients with survivin positive newly diagnosed glioblastoma multiforme (GBM) treated with at least 4 doses of SVN53-67/M57-keyhole limpet hemocyanin (KLH) peptide vaccine (SurVaxM) and standard of care temozolomide. SECONDARY OBJECTIVES: I. To determine the safety and tolerability of SurVaxM in patients receiving standard care adjuvant temozolomide. II. To evaluate overall survival (OS) in patients with survivin positive newly diagnosed GBM treated with SurVaxM and adjuvant temozolomide. III. To describe the immune response in patients treated with SurVaxM and predictors of response. IV. To evaluate objective tumor response rate (applicable only for patients with evaluable disease at study entry, as defined per Response Assessment in Neuro-Oncology \[RANO\] criteria) and predictors of response. OUTLINE: Patients receive the first priming dose of SVN53-67/M57-KLH peptide vaccine in emulsion with montanide ISA 51 subcutaneously (SC) and sargramostim SC within 7-28 days after completion of chemoradiation. Treatment repeats every 2 weeks for a total of 4 doses in the vaccine priming phase and then every 12 weeks during the adjuvant phase in the absence of disease progression or unacceptable toxicity. Patients also receive standard adjuvant temozolomide orally (PO) or intravenously (IV) on days 1-5. Treatment repeats every 28 days for 6 courses or more (at the discretion of the investigator) in the absence of disease progression or unacceptable toxicity. Patients may then receive maintenance SVN53-67/M57-KLH peptide vaccine in emulsion with montanide ISA 51 SC and sargramostim SC every 12 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 12 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
66
Correlative studies
Given SC
Given SC
Given SC
Given PO or IV
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States
Dana-Farber Harvard Cancer Center
Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States
Progression-free Survival (PFS)
The 6-month progression-free survival (PFS6) estimated using the Kaplan-Meier methods. PFS6 is defined as the percentage of patients without tumor progression or death from any cause 6 months after the date of diagnosis by biopsy. Corresponding confidence intervals will be computed.
Time frame: Date of diagnosis to the date of first observed disease progression or death due to any cause, assessed at 6 months
Immune Responses to SurVaxM and Predictors of Response
A series of exploratory analyses will initially take place including individual subject-level profile plots and overall mean plots used to examining the mean structure. Formal statistical examination of longitudinal patterns will be done through the use of a mixed model. Restricted maximum likelihood estimation will be utilized in the model fitting procedures. Once the model is fit, specific linear contrasts based on the estimated model parameters will be constructed and used to test hypotheses concerning between time point comparisons.
Time frame: Up to 30 days after completion of study treatment
Incidence of Grade 3 or 4 Toxicities, According to National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4
Toxicities will be summarized using simple frequencies by grade. CTEP Version 4 of the NCI Common Terminology Criteria for Adverse Events (CTCAE) will be utilized for AE reporting. Results are presented for the number of participants with drug-related Grade 3 or 4 toxicity/adverse event (AE). Grades range from 0 (none) to 5 (death), with Grade 3 and 4 being defined as follows: Grade 0 = No AE; Grade 1 = Mild AE; Grade 2 = Moderate AE; Grade 3 = Severe AE; Grade 4 = Life-threatening or disabling AE; Grade 5 = Death related to AE.
Time frame: Up to 30 days after completion of study treatment
Overall Survival
The median overall survival estimated using the Kaplan-Meier methods. Estimates of quantities such as median survival will be obtained. Corresponding confidence intervals will be computed.
Time frame: Date of diagnosis until (1) date of death or (2) the last date patient known alive (if death is not observed), assessed up to 2 years
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