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NCT Number: NCT03072134

Neural Stem Cell Based Virotherapy of Newly Diagnosed Malignant Glioma

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.

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Key information

Conditions

Glioma Adenoviridae Infections Anaplastic Astrocytoma Anaplastic Oligoastrocytoma Anaplastic Oligodendroglioma Astrocytoma Astrocytoma, Grade III Astrocytoma, Grade IV Brain Cancer Brain Diseases Brain Neoplasms Central Nervous System Diseases Central Nervous System Neoplasms DNA Virus Infections Glioblastoma Glioblastoma Multiforme Infections Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Nervous System Diseases Nervous System Neoplasms Neuroectodermal Tumors Oligodendroglioma Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

City of Hope, Duarte, California, United States

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Neural stem cells loaded with an oncolytic adenovirus

Biological

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

Primary outcomes

  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 outcomes

  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

Sponsors and collaborators

Lead sponsor

Northwestern University

Other

Collaborators

  • National Cancer Institute (NCI)

Registry information

Official study title

Neural Stem Cell Oncolytic Adenoviral Virotherapy of Newly Diagnosed Malignant Glioma

Important dates

Study start
2017
Primary completion
2020
Study completion
2021
First posted
Mar 7, 2017
Registry last updated
Jan 20, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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