Abstract
BackgroundDespite the combination of surgical resection, radio- and chemotherapy, median survival of glioblastoma multiforme (GBM) patients only slightly increased in the last years. Disease recurrence is definite with no effective therapy existing after tumor removal. Dendritic cell (DC) vaccination is a promising active immunotherapeutic approach. There is clear evidence that it is feasible, results in immunological anti-tumoral responses, and appears to be beneficial for survival and quality of life of GBM patients. Moreover, combining it with the standard therapy of GBM may allow exploiting synergies between the treatment modalities. In this randomized controlled trial, we seek to confirm these promising initial results.MethodsOne hundred and thirty-six newly diagnosed, isocitrate dehydrogenase wildtype GBM patients will be randomly allocated (1:1 ratio, stratified by O6-methylguanine-DNA-methyltransferase promotor methylation status) after near-complete resection in a multicenter, prospective phase II trial into two groups: (1) patients receiving the current therapeutic “gold standard” of radio/temozolomide chemotherapy and (2) patients receiving DC vaccination as an add-on to the standard therapy. A recruitment period of 30 months is anticipated; follow-up will be 2 years. The primary objective of the study is to compare overall survival (OS) between the two groups. Secondary objectives are comparing progression-free survival (PFS) and 6-, 12- and 24-month OS and PFS rates, the safety profile, overall and neurological performance and quality of life.DiscussionUntil now, close to 500 GBM patients have been treated with DC vaccination in clinical trials or on a compassionate-use basis. Results have been encouraging, but cannot provide robust evidence of clinical efficacy because studies have been non-controlled or patient numbers have been low. Therefore, a prospective, randomized phase II trial with a sufficiently large number of patients is now mandatory for clear evidence regarding the impact of DC vaccination on PFS and OS in GBM.Trial registrationProtocol code: GlioVax, date of registration: 17. February 2017.Trial identifier: EudraCT-Number 2017–000304-14.German Registry for Clinical Studies, ID: DRKS00013248 (approved primary register in the WHO network) and at ClinicalTrials.gov, ID: NCT03395587. Registered on 11 March 2017.
Highlights
Despite the combination of surgical resection, radio- and chemotherapy, median survival of glioblastoma multiforme (GBM) patients only slightly increased in the last years
Study endpoints The primary objective of the study is to determine whether survival of newly diagnosed GBM patients treated with lysate-loaded, mature Dendritic cell (DC) vaccines as add-on to the standard of care is superior to the treatment with the standard of care alone
DC vaccination with high-purity, tumor-lysate-loaded, mature DC will be fully integrated into standard therapy
Summary
Despite the combination of surgical resection, radio- and chemotherapy, median survival of glioblastoma multiforme (GBM) patients only slightly increased in the last years. There is clear evidence that it is feasible, results in immunological anti-tumoral responses, and appears to be beneficial for survival and quality of life of GBM patients. Combining it with the standard therapy of GBM may allow exploiting synergies between the treatment modalities. The established therapeutic standard in the first-line therapy for GBM combines maximal safe resection, fractionated radiotherapy with concomitant alkylating temozolomide (TMZ) chemotherapy followed by adjuvant TMZ. This multimodal approach has improved the survival of patients significantly. There is a clear need for novel therapeutic modalities
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