Intracerebral injection of CpG oligonucleotide for patients with de novo glioblastoma—A phase II multicentric, randomised study

Abstract Background Immunostimulating oligodeoxynucleotides containing unmethylated cytosine-guanosine motifs (CpG-ODN) have shown a promising efficacy in several cancer models when injected locally. A previous phase II study of CpG-ODN in patients with recurrent glioblastoma (GBM) has suggested some activity and has shown a limited toxicity. This multicentre single-blinded randomised phase II trial was designed to study the efficacy of a local treatment by CpG-ODN in patients with de novo glioblastomas. Patients and methods Patients with a newly diagnosed glioblastoma underwent large surgical resection and CpG-ODN was randomly administrated locally around the surgical cavity. The patients were then treated according to standard of care (SOC) with radiotherapy and temozolomide. The primary objective was 2-year survival. Secondary outcomes were progression free survival (PFS), and tolerance. Results Eighty-one (81) patients were randomly assigned to receive CpG-ODN plus SOC (39 patients) or SOC (42 patients). The 2-year overall survival was 31% (19%; 49%) in the CpG-ODN arm and 26% (16%; 44%) in the SOC arm. The median PFS was 9 months in the CpG-ODN arm and 8.5 months in the SOC arm. The incidence of adverse events was similar in both arms; although fever and post-operative haematoma were more frequent in the CpG-ODN arm. Conclusions Local immunotherapy with CpG-ODN injected into the surgical cavity after tumour removal and followed by SOC, although well tolerated, does not improve survival of patients with newly diagnosed GBM.