Neural Stem Cell Based Virotherapy of Newly Diagnosed Malignant Glioma

Sponsor

Northwestern University (Other)

Overall Status

Completed

CT.gov ID

NCT03072134

Collaborator

(none)

Enrollment

Locations

Arms

50.2

Actual Duration (Months)

6.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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 diganosed 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.

Condition or Disease	Intervention/Treatment	Phase
Glioma Anaplastic Astrocytoma Anaplastic Oligodendroglioma Anaplastic Oligoastrocytoma Glioblastoma Multiforme Astrocytoma, Grade III Astrocytoma, Grade IV Brain Cancer	Biological: Neural stem cells loaded with an oncolytic adenovirus	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

13 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Intervention Model Description:

A Phase I study of neural stem cell based virotherapy in combination with standard radiation and chemotherapy for patients with newly diagnosed malignant gliomaA Phase I study of neural stem cell based virotherapy in combination with standard radiation and chemotherapy for patients with newly diagnosed malignant glioma

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Neural Stem Cell Oncolytic Adenoviral Virotherapy of Newly Diagnosed Malignant Glioma

Actual Study Start Date :

Apr 24, 2017

Actual Primary Completion Date :

Apr 6, 2020

Actual Study Completion Date :

Jul 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Unresectable disease Patients with unresectable tumors will undergo a biopsy followed by injection of neural stem cells loaded with the virus and then receive standard chemoradiotherapy.	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. Other Names: NSC-CRAd-Survivin-pk7
Experimental: Resectable disease Patients with resectable tumors will undergo a resection followed by injection of neural stem cells loaded with the virus and then receive standard chemoradiotherapy.	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. Other Names: NSC-CRAd-Survivin-pk7

Arm

Intervention/Treatment

Experimental: Unresectable disease

Patients with unresectable tumors will undergo a biopsy followed by injection of neural stem cells loaded with the virus and then receive standard chemoradiotherapy.

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.

Other Names:

NSC-CRAd-Survivin-pk7

Experimental: Resectable disease

Patients with resectable tumors will undergo a resection followed by injection of neural stem cells loaded with the virus and then receive standard chemoradiotherapy.

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.

Other Names:

NSC-CRAd-Survivin-pk7

Outcome Measures

Primary Outcome Measures

Determine the maximum number of neural stem cells loaded with the oncolytic adenovirus. [Two years]
We will escalate the number of neural stem cells loaded with the oncolytic adenovirus in each cohort of patients and monitor the neurological exam for development of any neurological side effects.

Secondary Outcome Measures

Assessment of tumor response or progression to treatment on MRI. [Two years]
We will monitor patients with serial MRIs over the course of the study to determine whether there is any evidence of tumor regression or progression.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients must have presumed malignant glioma based on clinical and radiologic evaluation (pathologic confirmation of malignant glioma must be made at the time of stereotactic biopsy or resection prior to NSC-CRAd-S-pk7 injection; if this is not possible, the injection will not be performed and the subject will no longer be eligible for the study).
Tumor must be accessible for injection and must not be located in the brainstem, or contained within the ventricular system.
Planning to undergo standard radiation/chemotherapy
18 years of age or older.
Performance status must be KPS ≥ 70
SGOT (AST) < 3x upper limit of normal
Serum creatinine < 2mg/dl
Platelets > 100,000/mm3 and WBC > 3000/mm3

Exclusion Criteria:

Prior or ongoing liver disease including known cirrhosis, hepatitis B or C infection but not to exclude patients with a distant history of resolved hepatitis A infection.
Immunosuppressive drugs (with exception of corticosteroid).
Known HIV+ patients.
Acute infections (viral, bacterial or fungal infections requiring therapy).
Pregnant or breast-feeding patients.
Evidence of metastatic disease or other malignancy (except squamous or basal cell skin cancers).
Prior radiation therapy to the brain or prior treatment for brain tumor Other serious co-morbid illness or compromised organ function.