Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-24 @ 5:44 PM
Ignite Modification Date:
2025-12-24 @ 5:44 PM
NCT ID:
NCT03896568
Brief Summary:
This phase I trial studies best dose and side effects of oncolytic adenovirus DNX-2401 in treating patients with high-grade glioma that has come back (recurrent). Oncolytic adenovirus DNX-2401 is made from the common cold virus that has been changed in the laboratory to make it less likely to cause an infection (such as a cold). The virus is also changed to target brain cancer cells and attack them.
Detailed Description:
PRIMARY OBJECTIVES:
I. To determine the maximal tolerated dose (MTD) of allogeneic bone marrow-derived human mesenchymal stem cells (BM-hMSCs) loaded with the oncolytic adenovirus DNX-2401 (BM-hMSCs-DNX2401) administered by intra-arterial injection (i.e., transfemoral endovascular intracranial injection) in patients with recurrent glioblastoma (GBM), IDH-mutant astrocytoma grade 4, gliosarcoma, or wild-type IDH-1 anaplastic astrocytoma.
II. To determine the local and systemic toxicity of allogeneic BM-hMSCs-DNX2401 administered by intra-arterial injection (i.e., transfemoral endovascular intracranial injection) in patients with recurrent GBM, gliosarcoma or wild-type IDH-1 anaplastic astrocytoma.
III. To determine at the molecular and cellular level the capacity of allogeneic BM-hMSCs-DNX2401 administered intra-arterially to home to and deliver DNX-2401 to recurrent GBM, gliosarcoma or wild-type IDH-1 anaplastic astrocytoma by analyzing post-treatment surgical brain tumor specimens for the expression and distribution of adenoviral proteins.
SECONDARY OBJECTIVES:
I. To assess shedding of adenovirus into the blood, sputum, and nasopharynx after intra-arterial administration of BM-hMSCs-DNX2401 in patients with recurrent GBM, gliosarcoma or wild-type IDH-1 anaplastic astrocytoma.
II. To assess the development of anti-adenovirus antibodies after intra-arterial administration of BM-hMSCs-DNX2401 in patients with recurrent GBM, gliosarcoma or wild-type IDH-1 anaplastic astrocytoma.
III. To evaluate immune-mediated cytokine responses after intra-arterial administration of BM-hMSCs-DNX2401 in patients with recurrent GBM, gliosarcoma or wild-type IDH-1 anaplastic astrocytoma.
IV. To assess anti-tumoral activity and to determine progression-free survival (PFS) and overall survival (OS) after intra-arterial administration of BM-hMSCs-DNX2401 in patients with recurrent GBM, gliosarcoma or wild-type IDH-1 anaplastic astrocytoma.
OUTLINE: This is a dose-escalation study.
PART I: Patients receive one or two infusions of BM-hMSCs-DNX-2401 intra-arterially (IA) over 20-30 minutes on day 0. Dose level 1-5 will receive 1 infusion. Dose level 6 will receive 2 infusions.
PART II: Patients receive one or two infusions BM-hMSCs-DNX-2401 IA, depending on the highest dose that was tolerated in Part 1. After 2 weeks, patients undergo surgery where the tumor is removed, then receive intramural injection of BM-hMSCs-DNX-2401 into the resection cavity.
After completion of study treatment, patients in both part I and II are followed up on days 1, 4, 7, and 14 of month 1,every 6 weeks for 6 months (4 visits), then every 8 weeks for 1 year (6 visits), then every 4 months for 1 year (3 visits), then every 6 months until the tumor grows back. Patients treated at Dose level 6 in Part 1 and Part 2 are also followed up on Day 12, then on Day 1, 4, and 7 after second infusion, then on Day 1, 7, and 14 post-craniotomy for Part 2, Dose Level 6, then ,every 6 weeks for 6 months (4 visits), then every 8 weeks for 1 year (6 visits), then every 4 months for 1 year (3 visits), then every 6 months until the tumor grows back.
Study:
NCT03896568
Study Brief:
Protocol Section:
NCT03896568