NCT03072134

Neural Stem Cell Based Virotherapy of Newly Diagnosed Malignant Glioma

Neural Stem Cell Oncolytic Adenoviral Virotherapy of Newly Diagnosed Malignant Glioma

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: Northwestern University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Malignant gliomas have a very poor prognosis with median survival measured in months rather than years. It is a disease in great need of novel therapeutic approaches. Based on the encouraging results of our preclinical studies which demonstrate improved efficacy without added toxicity, the paradigm of delivering a novel oncolytic adenovirus via a neural stem cell line in combination with radiation and chemotherapy is well-suited for evaluation in newly diagnosed malignant gliomas. The standard-of-care allows application of virotherapy as neoadjuvant therapy and assessment of the cooperative effects with radiation/chemotherapy without altering the standard treatment.

Detailed description

This is an open-label, phase 1, dose escalation trial that followed a 3x3 design. Three doses will be evaluated in the resectable cohorts: Cohort 1: 0.5x10\^8 NSCs loading 6.25x10\^10 vp; Cohort 2: 1.0x10\^8 NSCs loading 1.25x10\^11 vp; and Cohort 3: 1.5x10\^8 NSCs loading 1.875x10\^11 vp. Subjects enrolled have newly diagnosed high-grade glioma based on clinical and radiologic criteria; pathology will be confirmed at the time of surgical resection. Direct intra-tumoral injection of study product (NSC-CRAd-S-p7) will be done after resection but prior to closure. Subjects will then receive concomitant radiotherapy (RT) at a dose of 60Gy and chemotherapy with temozolomide (TMZ), 75 mg/m2, daily during RT. This will be followed by adjuvant TMZ dosed at 200 mg/m2 for 6 cycles. Subjects will be followed until disease progression with serial brain MRIs, and for survival up to 5 years. The non-resectable cohort will not opened due to limited product availability.

Conditions

• Glioma
• Anaplastic Astrocytoma
• Anaplastic Oligodendroglioma
• Anaplastic Oligoastrocytoma
• Glioblastoma Multiforme
• Astrocytoma, Grade III
• Astrocytoma, Grade IV
• Brain Cancer

Interventions

Type	Name	Description
BIOLOGICAL	Neural stem cells loaded with an oncolytic adenovirus	The primary objectives are to evaluate the safety of the combined therapy and determine the maximum tolerated dose (MTD) for a future Phase II study.

Timeline

• Start date: 2017-04-24
• Primary completion: 2020-04-06
• Completion: 2021-07-01
• First posted: 2017-03-07
• Last updated: 2023-01-20
• Results posted: 2023-01-20

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study