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Neural Stem Cell Based Virotherapy of Newly Diagnosed Malignant Glioma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03072134
Recruitment Status : Completed
First Posted : March 7, 2017
Results First Posted : January 20, 2023
Last Update Posted : January 20, 2023
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Maciej Lesniak, Northwestern University

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 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.

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

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 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 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 : April 24, 2017
Actual Primary Completion Date : April 6, 2020
Actual Study Completion Date : July 1, 2021


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 Name: 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 Name: NSC-CRAd-Survivin-pk7




Primary Outcome Measures :
  1. Percentage of Dose-limiting Toxicities [ Time Frame: Two years ]
    Using a 3+3 dose escalation design, three to six patients were to be enrolled per dose in each of the 3 cohorts. If no patients in the cohort experienced a dose-limiting toxicity (DLT), then the next cohort enrolled a minimum of 3 patients. If one of three patients experienced a DLT, then 3 more patients were evaluated at that dose level. If none of these three additional patients experienced a DLT, then dose escalation occurs, unless this is the highest dose, in which case dose escalation is stopped and the highest dose is declared the MTD. If 1 or more of these additional 3 patients had a DLT, then three additional patients may be entered, after discussion with the sponsor, at the next lowest does level if only three patients were treated previously at that dose. If two or more patients experienced a DLT Dose escalation will be stopped; 3 more patients could be added with sponsor approval at the next lower dose level.


Secondary Outcome Measures :
  1. Assessment of Tumor Response. [ Time Frame: Two years ]
    Per Response Assessment in Neuro-Oncology Criteria (RANO, 2017) for target lesions as assessed by MRI: Complete Response (CR): The enhancing tumor is no longer seen by neuroimaging; Partial Response (PR): Decrease of ≥ 50% in the product of two diameters with the patient on a stable or decreasing dose of steroids; Minor Response (MR): Decrease in diameter products of < 50% with the patient on a stable or decreasing dose of steroids; Stable Disease (SD): The scan shows no change. Patients should be receiving stable or decreasing doses of steroids; Progression (P): Increase of > 25% in tumor area (two diameters) provided that the patient has not had his/her dose of steroids decreased since the last evaluation period. A concomitant decrease in steroid dose will rule out a progression designation during the first two months after completion of radiation; Pseudoprogression (PP): Radiological changes without concomitant neurological changes.

  2. Progression-free Survival [ Time Frame: two years ]
    Median progression-free survival

  3. Overall Survival [ Time Frame: Two years ]
    Median overall survival



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03072134


Locations
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United States, California
City of Hope
Duarte, California, United States, 91010
United States, Illinois
Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Northwestern University
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Maciej S Lesniak, MD Northwestern University
  Study Documents (Full-Text)

Documents provided by Maciej Lesniak, Northwestern University:
Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Maciej Lesniak, Professor and Chairman, Northwestern University
ClinicalTrials.gov Identifier: NCT03072134    
Other Study ID Numbers: STU00203933
5P50CA221747-05 ( U.S. NIH Grant/Contract )
First Posted: March 7, 2017    Key Record Dates
Results First Posted: January 20, 2023
Last Update Posted: January 20, 2023
Last Verified: December 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Maciej Lesniak, Northwestern University:
Neural Stem Cells
Glioma
Glioblastoma
Astrocytoma
Brain Cancer
New Diagnosed Glioma
Temozolomide
Radiation
Virotherapy
Adenovirus
Oncolytic virotherapy
Additional relevant MeSH terms:
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Neoplasms, Germ Cell and Embryonal
Glioblastoma
Glioma
Astrocytoma
Oligodendroglioma
Brain Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases