Anti-Cancer Effects of Carvedilol With Standard Treatment in Glioblastoma and Response of Peripheral Glioma Circulating Tumor Cells

Study Overview
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Brief Summary
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The purpose of this pilot study is to evaluate the addition of carvedilol with standard of care treatment to determine if it will improve progression-free survival in the front line setting in patients with glioblastoma multiforme (GBM). In addition, monitoring of circulating tumor cells (CTCs) by a real-time reverse transcriptase polymerase chain reaction (qRT-PCR) assay to correlate with the clinical findings.

Detailed Description
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This is a pilot study to assess efficacy of the addition of a non-selective beta-blocker to standard of care treatment in the front-line setting of glioblastoma multiforme. And to also evaluate the level of peripheral glioma circulating tumor cells via TeleomeScan assay to correlate disease response determined by neuro-imaging. Peripheral blood samples will be collected at baseline, on day 1 of cycle 1 and then after on day 1 of cycle 4 and at the end of cycle 6 of adjuvant chemotherapy. in order to correlate the biological effects of treatment response. The investigators will evaluate the quantity of peripheral glioma circulating tumor cells and want to apply the information seen in the periphery to the status of the cancer on imaging studies. Subjects will start oral carvedilol at 6.25 mg orally twice daily and will evaluate the patient and vital status if they tolerate this dose at 1-2 weeks after initiation. If tolerated well, will increase the dose to the maximum anticipation of 12.5 mg orally twice daily. Treatment will proceed for 6 cycles and carvedilol will stop at the end of 6 cycles. Patients will be monitored with neuroimaging prior before chemoradiotherapy, before adjuvant temozolomide and every 2 months on adjuvant temozolomide. Following the completion of 6 cycles of adjuvant therapy, patients will continue to receive neuroimaging on every 3 months' basis until disease progression based upon standard of care.

Official Title
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A Pilot Study: Evaluating the Anti-Cancer Effects of Carvedilol With TTFields and Standard of Care in Glioblastoma and Response of Peripheral Glioma Circulating Tumor Cells

Conditions
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Glioblastoma, Glioblastoma Multiforme

Intervention / Treatment
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* Drug: Carvedilol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have histologically or cytologically confirmed WHO Grade IV Glioblastoma Subjects must have not received previous chemotherapy or radiation therapy for GBM Subjects must have systolic blood pressure greater than or equal to 90 and heart rate >59 Subjects who are on beta-blockers for other etiologies may enroll on study and switch therapy to carvedilol if deemed medical appropriate per treating physician Exclusion Criteria: Subjects receiving any other investigational agents Subjects who have severe and uncontrolled asthma, COPD Systolic blood pressure <90 mmHg or HR <60 bpm without antihypertensive medications at baseline Subjects with uncontrolled illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Allergy to beta blockers

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Carvedilol + Standard Treatment<br>Subjects will receive carvedilol starting at 6.25 mg orally (PO) twice daily for 1-2 weeks and if tolerated will then be increased to 12.5 mg PO twice daily starting on day 1 of concurrent chemoradiotherapy and continue daily until the end of adjuvant cycle 6 of temozolomide and Tumor Treated Fields. | Drug: Carvedilol<br>* Carvedilol: Start at 6.26 mg PO twice daily for 1-2 weeks and if tolerated, will be increased to 12.5 mg PO twice daily for 6 cycles as tolerated.<br>* Other names: Coreg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival curve of overall survival | Kaplan-Meier curves for overall survival in order to see if the addition of carvedilol to standard of care appears promising from a clinical standpoint | From start of carvedilol treatment until the date of first documented progression or death which ever comes first (approximately 6-15 months) | 
| Survival curve of progression free survival | Kaplan-Meier curves for progression free survival in order to see if the addition of carvedilol to standard of care appears promising from a clinical standpoint | From start of carvedilol treatment until the date of first documented progression or death which ever comes first (approximately 6-15 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantify Circulating Tumor Cells (CTCs) | Quantify CTCs via qRT-PCR assay and to assess how the trend of CTCs correspond to disease status as measured by RANO criteria on neuro-imaging. | Baseline (prior to any treatment), Cycle 1 Day 1, Cycle 4 day 1, End of cycle 6 of Chemotherapy (each cycle is 28 days) |