NCT01956734

Virus DNX2401 and Temozolomide in Recurrent Glioblastoma

Phase I Trial of Combination of DNX-2401 (Formerly Named Delta-24-RGD) Oncolytic Adenovirus With a Short Course of Temozolomide for Treatment of Glioblastoma at First Recurrent

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 31 (estimated)
• Sponsor: Clinica Universidad de Navarra, Universidad de Navarra · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

Phase I trial, unicentric, uncontrolled. Intratumoral injection or intramural (into the resected tumor cavity) of DNX2401 into brain tissue will be followed by up to two 28 - day cycles of oral temozolomide (TMZ) in schedule of 7 days on/7 days off to evaluate safety of the combination. Completion of two full cycles of TMZ will be dependent upon tolerance and toxicity. The rationale in using the virus with chemotherapy begins with the lessons learned in many clinical trials in glioblastoma (GBM) about both the great difficulty of treating this disease with monotherapy and the limitations of the therapeutic virus. The best clinical results in recent years have been achieved with combinations of multiple therapeutics efforts, including, maximum resection and chemotherapy, immunotherapy and targeted therapies. There are very strong preclinical data about the synergy of DNX-2401 and TMZ proposed in our trial design. The dose-dense schemes of TMZ like the one we will use, have been developed with the aim to saturate o6-methylguanine-DNA-methyltransferase (MGMT). The published results to date have shown reasonable toxicity albeit with modest efficacy' these schemes are now in phase III trials. In addition, autophagy triggered by TMZ could help viral replication in the tumor cells 11. The last argument in favor of this virus + TMZ combination is the proved efficacy in killing GBM tumor stem cells. In vitro and animals models have shown this combination is much more effective that any of the treatments alone against GBM stem cells and the tumors derived from them.

Detailed description

DNX2401 will be injected after stereotactic biopsy reveals intraoperative pathology confirming the presence of recurrent glioblastoma. The injection will be either intratumoral or intramural with injections throughout the post-resection cavity.

Conditions

• Glioblastoma Multiforme
• Recurrent Tumor

Interventions

Type	Name	Description
PROCEDURE	DNX2401 and Temozolomide	Virus injection in the brain parenchyma after pathology confirmation of recurrent glioblastoma. Temozolomide oral 14 days after virus injection.

Timeline

• Start date: 2013-09-01
• Primary completion: 2015-12-01
• Completion: 2017-03-01
• First posted: 2013-10-08
• Last updated: 2017-10-24

Locations

1 site across 1 country: Spain