Neural Stem Cell Based Virotherapy of Newly Diagnosed Malignant Glioma
Condition: Glioma; Anaplastic Astrocytoma; Anaplastic Oligodendroglioma; Anaplastic Oligoastrocytoma; Glioblastoma Multiforme; Astrocytoma, Grade III; Astrocytoma, Grade IV; Brain Cancer
MeSH terms: Glioblastoma; Glioma; Astrocytoma; Oligodendroglioma; Brain Neoplasms
Intervention: Neural stem cells loaded with an oncolytic adenovirus
Intervention description: 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.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
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)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Glioma; Glioblastoma; Astrocytoma; Brain Cancer; New Diagnosed Glioma; Temozolomide; Radiation; Neural Stem Cells; Virotherapy; Adenovirus; Oncolytic virotherapy

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.
    

Eligibility 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.