Combination Drug Therapy for Personalized Cancer Stem Cell High-Throughput Drug Screening for Glioblastoma

Study Overview
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Brief Summary
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Proposed treatment of subjects with newly diagnosed glioblastoma with novel personalized drug regimens identified to be effective in vitro using cancer stem cells derived from their individual tumors, alongside standard of care radiation and TMZ.

Detailed Description
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A panel of FDA approved drugs will be tested by high throughput screening, which is CLIA certified allowing for clinical decisions based on the results, to identify a combination of up to 3 drug candidates for treating individual patients. Lead candidates will be evaluated by pharmacists and a team of physicians, to confirm that prescribed drugs do not utilize pharmacological/ metabolic pathways that are known to increase the likelihood of toxicity, prior to initiating treatment. Investigational drug therapy, targeting CSCs, will be initiated alongside standard of care chemoradiation with TMZ.

Official Title
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A Phase 1 Study of Combination Drug Therapy Based on Personalized Cancer Stem Cell (CSC) High-Throughput Drug Screening (HTS) With Standard of Care for Newly Diagnosed Glioblastoma

Conditions
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Newly Diagnosed Glioblastoma

Intervention / Treatment
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* Drug: combinations of up to 3 FDA approved drugs from a panel of compounds


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological diagnosis of GBM (WHO grade 4) Subjects ≥18 years of age Patients must have a life expectancy of >6 months Patients must have a surgically accessible tumor with the intent for a gross or near total resection of the tumor mass (GBM, WHO grade 4) Patients must have a KPS rating of ≥70 Patients should not have received any prior systemic anti-cancer therapy Patients must be negative for HIV, Hepatitis B and C Baseline hematologic studies and chemistry and coagulation profiles must meet the following criteria: Hemoglobin (Hgb)> 8 g/dL Absolute Neutrophil Count (ANC) > 1,000/mm3 Platelet count > 100,000/mm3 Creatinine < 2 mg/dL Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) < 3x upper limit of normal (ULN) Exclusion Criteria: Metastatic disease Diseases or conditions that obscure toxicity or dangerously alter drug metabolism Serious intercurrent medical illness Inadequately controlled hypertension History of myocardial infarction or unstable angina within 6 months History of stroke or transient ischemic attack within 6 months

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: single-center Phase 1 open-label study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Personalized Combination Drug Therapy for Cancer Stem Cells<br>Administer combinations of up to 3 FDA approved drugs from a panel of compounds selected based on high throughput screening | Drug: combinations of up to 3 FDA approved drugs from a panel of compounds<br>* personalized drug combinations<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| determine safety of CSC/HTS-based combination drug therapy | incidence of treatment-related AEs, laboratory abnormalities, and SAEs as assessed by CTCAE version 5.0 | From date of first dose of investigational drug regimen until date of first documented progression or death from any cause, whichever came first, assessed up to 24 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of CSC/HTS-based combination drug therapy | Response assessment per Response Assessment in Neuro-Oncology (RANO) criteria | From inclusion in the study up to approximately 36 months | 
| Efficacy of CSC/HTS-based combination drug therapy | Progression-free survival (PFS) | From inclusion in the study until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 36 months | 
| Efficacy of CSC/HTS-based combination drug therapy | Median overall survival (OS) | From inclusion in the study until date of death from any cause, assessed up to approximately 36 months |