A phase II clinical trial of poly-ICLC with radiation for adult patients with newly diagnosed supratentorial glioblastoma: a North American Brain Tumor Consortium (NABTC01-05)

Abstract

Purpose This phase II study was designed to determine the overall survival time of adults with supratentorial glioblastoma treated with the immune modulator, polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly-ICLC), in combination with and following radiation therapy (RT). Methods and Materials This was an open-label, single arm phase II study. Patients were treated with RT in combination with poly-ICLC followed by poly-ICLC as a single agent. Poly-ICLC was initiated 7–28 days after the surgical procedure that established the diagnosis; radiotherapy began within 7 days of the first dose of poly-ICLC and within 35 days of surgical diagnosis. Treatment with poly-ICLC continued following the completion of RT to a maximum of 1 year or until tumor progression. Results 31 patients were enrolled in this study. One patient did not have a GBM and was deemed ineligible. For the 30 eligible patients, time to progression was known for 27 patients and 3 were censored. The estimated 6-month progression free survival was 30% and the estimated 1-year progression-free survival was 5%. Median time to progression was as 18 weeks. The 1-year survival was 69% and the median survival was 65 weeks. Conclusions The combined therapy was relatively well tolerated. This study suggests a survival advantage compared to historical studies using RT without chemotherapy but no survival advantage compared to RT with adjuvant nitrosourea or non-temozolomide chemotherapy. Our results suggest that poly-ICLC has activity against glioblastoma and may be worth further study in combination with agents such as temozolomide.

Advances in the Treatment of Malignant Gliomas

“…Two phase 2 studies with poly ICLC suggested survival advantage awaiting further confirmation [45,46].…”

Dendritic Cell Vaccines for Cancer Therapy: Fundamentals and Clinical Trials

“…Antitumor response was associated with activation of 2′5′-oligoadenylate synthetases, which are antiviral proteins induced by type I IFN [ 143 ]. In another study, 30 adult patients with glioblastoma multiforme received poly-ICLC in combination with radiotherapy, thereby demonstrating an advantage in relation to historical studies using radiotherapy alone [ 144 ]. Okada's group is currently analyzing the effect of associating poly-ICLC with DC vaccines generated under INF−α(αDC1), previously shown to be more effective than conventional DCs at inducing an antigen-specifi c CTL response [ 145 ].…”

Dual Role of TLR3 in Inflammation and Cancer Cell Apoptosis

“…Poly-ICLC is also used in combination with radiotherapy for low-grade recurrent B and T cell lymphoma, and for brain and central nervous system tumors in phase I and II clinical phase. Interestingly, a phase II clinical trial from the North American Brain Tumor Consortium for 30 patients with newly diagnosed supratentorial glioblastoma showed that treatment with radiotherapy in combination with Poly-ICLC followed by Poly-ICLC as a single agent was relatively well-tolerated and enhanced the survival of patients compared to historical studies using radiotherapy alone [95]. Then, the New Approaches to Brain Tumor Therapy (NABTT) consortium assigned 365 patients with newly diagnosed glioblastoma in phase II clinical trial for testing novel agents in combination with radiation + temozolomide and compared the results with the data from the European Organization for Research and Treatment of Cancer (EORTC) phase II study [96,97].…”