Carvedilol With Chemotherapy in Second Line Glioblastoma and Response of Circulating Tumor Cells

Overview

Subjects will receive standard chemotherapy and Tumor Treated Fields (TTFields) and will also receive Carvedilol for 4 cycles of treatment. Carvedilol will start at 6.25 mg orally twice a day and be increased to 12.5 mg orally twice daily after 1 to 2 weeks if tolerated. Peripheral glioma circulating tumor cells (CTC) and brain MRI with and without contrast will be obtained at baseline, 2 cycles, and 4 cycles to determine the efficacy and direction of change of the CTC using a new assay tool. Preliminary assessment of the tolerability of Carvedilol with standard chemotherapy will also be evaluated.

Full Title of Study: “A Feasibility Study: Evaluating Carvedilol With Chemotherapy in Second Line Glioblastoma Multiforme and Response of Peripheral Glioma Circulating Tumor Cells”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 31, 2019

Detailed Description

This will be a feasibility study to assess the use of a new PCR assay with response to standard chemotherapy treatment in the second line setting in glioblastoma multiforme (GBM). The change in direction with the combination of carvedilol with standard of chemotherapy based upon brain MRI results will be assessed and associating that with also the change in the quantity of tumor cells with a new invented assay device. Six subjects will be enrolled in the study who have recurrent GBM and will be receiving second line treatment.

The subjects will receive standard therapy per the discretion of the treating oncologist. Carvedilol will start at 6.25 mg orally twice daily for 1-2 weeks to confirm tolerance. The subjects will then receive carvedilol at 12.5 mg orally twice daily as the maximum dose and take it continuously for 4 cycles of therapy. At the completion of 4 cycles, patients will stop taking carvedilol. If the patients were on previous anti-hypertensive medications, they will be instructed to restart those medications if stopped on this trial for carvedilol.

Peripheral blood samples will be collected at baseline before initiation of treatment, on first day of every cycle for four cycles and after the last cycle is completed to obtain peripheral glioma circulating tumor levels. Subjects will be re-evaluated for response every 2 cycles of therapy with brain MRI with and without contrast.

Interventions

  • Drug: Carvedilol
    • Carvedilol orally starting at 6.25 mg and increasing to 12.5 mg if tolerated after 1-2 weeks for a total of 4 cycles of treatment.

Arms, Groups and Cohorts

  • Experimental: Cohort 1
    • Carvedilol orally with standard chemotherapy starting at 6.25 mg and increasing to 12.5 mg if tolerated after 1-2 weeks for a total of 4 cycles of treatment.

Clinical Trial Outcome Measures

Primary Measures

  • Identify the correlation between our new RT-qPCR assay for circulating tumor cells and the change in responses in patients on treatment to MRI results.
    • Time Frame: Baseline, end of cycle 2, end of cycle 4, approximately 6 months depending on treatment plan
    • Identify the correlation between our new RT-qPCR assay for circulating tumor cells and the change in responses in patients on treatment to MRI results. We will use 1 to indicate progression of disease seen on brain MRI, 2 to indicate stability or no change in imaging, and 3 to indicate response to treatment. The correlation will be assessed by Spearman’s Rank Correlation coefficient. We will have six patients on this study which will give us 12 changed measurements.

Secondary Measures

  • Evaluate response with the addition of carvedilol to standard chemotherapy in the second line treatment in glioblastoma multiforme
    • Time Frame: Baseline, end of cycle 2, end of cycle 4, approximately 6 months depending on treatment plan
    • Evaluate response with the addition of carvedilol to standard chemotherapy in the second line treatment in glioblastoma multiforme. Evaluate the correlation between changes in measurements derived from this new assay with changes in a numerical scale based upon brain MRI results. We will use 1 to indicate progression of disease seen on brain MRI, 2 to indicate stability or no change in imaging, and 3 to indicate response to treatment. The correlation will be assessed by Spearman’s Rank Correlation coefficient. We will have six patients on this study which will give us 12 changed measurements. We are evaluating the changes of responses in patients on treatment to MRI results and correlate those with our new RT-qPCR assay for circulating tumor cells.
  • Evaluate incidents of adverse events during the time subjects are taking carvedilol with chemotherapy
    • Time Frame: From Baseline to 30 days after stopping carvedilol.
    • Evaluate adverse events during the time subjects are taking carvedilol with chemotherapy

Participating in This Clinical Trial

Inclusion Criteria

  • Grade IV Glioblastoma, receiving chemotherapy with or without TTfields.
  • Progressive or recurrent disease requiring second line treatment
  • evidence of progression of disease by brain MRI and are planned to receive chemotherapy

Exclusion Criteria

  • Current use of another beta blocker that cannot be switched to carvedilol at the onset of the trial.
  • Systolic blood pressure <90 mmHg and/or heart rate <60 bpm without hypertensive medications
  • Allergy to beta blockers
  • Severe or uncontrolled asthma or COPD (chronic obstructive pulmonary disease)

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • West Virginia University
  • Collaborator
    • West Virginia Clinical and Translational Science Institute
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Joanna Kolodney, MD, Principal Investigator, West Virginia University
  • Overall Contact(s)
    • Sylvia McEwuen, RN, 304-293-1683, smcewuen@hsc.wvu.edu

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