Predicting Response Patterns to Treatment in Glioblastoma (GBM) Patients

Study Overview
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Brief Summary
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PROPHETIC GBM - Predicting response patterns to treatment in Glioblastoma (GBM) oncology patients based on host response evaluation during anti-cancer treatments

Detailed Description
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The goal of this research study is identify new host response proteins, pathways and mechanisms that are associated with responsiveness to GBM treatment modalities. This will serve as a tool for physicians when making treatment decisions. The investigators also aim to identify the metabolic pathways that could lead to better therapeutic options. The patients will be given their treatment according to the institute's standard of care. The patients will provide up to 5 blood samples and clinical data will be collected from their medical records. The data obtained from the blood samples and the medical records of the patients will be used to search for potential mechanisms that are involved in response to treatment, and to identify potential targets to increase the response, and hence, increase treatment effectiveness or suggest potential new treatments.

Official Title
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Predicting Response Patterns to Treatment in Glioblastoma (GBM) Oncology Patients Based on Host Response Evaluation During Anti-cancer Treatments

Conditions
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Glioblastoma

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of informed consent prior to any study-specific procedures. Male or female aged at least 18 years. KPS not less than 50. Normal hematologic, renal and liver function: Absolute neutrophil count above 1500/mm3, platelets above 100,000/mm3, hemoglobin above 9 g/dL; Creatinine concentration not more than 1.4 mg/dL, or creatinine clearance above 40 mL/min; Total bilirubin below 1.5 mg/dL, ALT+ AST levels not more than 3 times above the upper normal limit. Patients planned to receive standard of care TMZ+RT treatment; TTF therapy during RT is permitted. Exclusion Criteria: Any concurrent and/or other active malignancy that has required systemic treatment within 2 years of surgery. Except for basal cell carcinomas and squamous cell carcinomas that have been completely excised and considered cured at least 12 months prior to screening, and carcinoma in situ of the cervix that have been completely excised and cured at least 5 years prior to screening. Participation in another clinical trial which includes an investigational drug. Generalized impairment or mental incompetence that would render the patient unable to understand his/her participation in the study. Pregnancy.

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| GBM patients<br>Newly diagnosed patients above 18 years of age with GBM receiving standard of care, i.e., maximal surgical resection possible followed by radiation therapy (RT) plus temozolomide (TMZ) therapy and maintenance TMZ. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to treatment | complete remission (CR); partial remission (PR), stable disease (SD), progressive disease (PD), suspected pseudo-progression, as defined by RANO | One month after completion of TMZ + RT | 
| Response to treatment | CR, PR, SD, PD, suspected pseudo-progression, as defined by RANO | 3 months after treatment completion in the first year | 
| Response to treatment | CR, PR, SD, PD, suspected pseudo-progression, as defined by RANO | 6 months after treatment completion in the first year | 
| Response to treatment | CR, PR, SD, PD, suspected pseudo-progression, as defined by RANO | 9 months after treatment completion in the first year | 
| Response to treatment | CR, PR, SD, PD, suspected pseudo-progression, as defined by RANO | 12 months after treatment completion in the first year | 
| Response to treatment | CR, PR, SD, PD, suspected pseudo-progression, as defined by RANO | 18 months after treatment completion in the first year | 
| Response to treatment | CR, PR, SD, PD, suspected pseudo-progression, as defined by RANO | 24 months after treatment completion in the first year | 
| Response to treatment | CR, PR, SD, PD, suspected pseudo-progression, as defined by RANO | 30 months after treatment completion in the first year | 
| Response to treatment | CR, PR, SD, PD, suspected pseudo-progression, as defined by RANO | 36 months after treatment completion in the first year | 
| Blood levels of proteins | Blood levels of proteins representing the Host response at baseline | Pre-chemoradiation therapy - 7 days or less before the first administration | 
| Blood levels of proteins | Changes in Blood levels of proteins representing the Host response compared to baseline | After the first chemoradiation administration - at least 24 h after the first temozolomide (TMZ) dose, and between 24-48 h after the first radiation therapy (RT) dose | 
| Blood levels of proteins | Changes in Blood levels of proteins representing the Host response compared to baseline | 21+/-2 days after the first TMZ dose | 
| Blood levels of proteins | Changes in Blood levels of proteins representing the Host response compared to baseline | At first detection of progressive disease (PD) based on MRI evaluation during follow-up assessed up to 36 months | 
| Blood levels of proteins | Changes in Blood levels of proteins representing the Host response compared to baseline | If the previous detection of progression turned out to be pseudo-progression, then an additional blood sample should be drawn at time of progression, assessed up to 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS | Overall survival | Until death or 3 years | 
| PFS | Progression free survival | up to 3 years |