Clinical trial NCT05380349: Personalized Cancer Stem Cell High-Throughput Drug Screening for Glioblastoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Newly Diagnosed Glioblastoma
Lead sponsor: Swedish Medical Center
Sponsor class: OTHER
First posted: 2022-05-18
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: single-center Phase 1 open-label study
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: determine safety of CSC/HTS-based combination drug therapy
timeFrame: 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 outcomes:
measure: Efficacy of CSC/HTS-based combination drug therapy
timeFrame: From inclusion in the study up to approximately 36 months
measure: Efficacy of CSC/HTS-based combination drug therapy
timeFrame: 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
measure: Efficacy of CSC/HTS-based combination drug therapy
timeFrame: From inclusion in the study until date of death from any cause, assessed up to approximately 36 months
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
Study officials:
affiliation: Ivy Center for Advanced Brain Tumor Treatment
name: Charles S Cobbs
role: PRINCIPAL_INVESTIGATOR
References: