Description:
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.
Title
- Brief Title: Carvedilol With Chemotherapy in Second Line Glioblastoma and Response of Circulating Tumor Cells
- Official Title: A Feasibility Study: Evaluating Carvedilol With Chemotherapy in Second Line Glioblastoma Multiforme and Response of Peripheral Glioma Circulating Tumor Cells
Clinical Trial IDs
- ORG STUDY ID:
WVU010318
- NCT ID:
NCT03861598
Conditions
- Glioblastoma Multiforme
- Glioblastoma
Interventions
| Drug | Synonyms | Arms |
|---|
| Carvedilol | Coreg, Coreg CR | Cohort 1 |
Purpose
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.
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Cohort 1 | Experimental | 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. | |
Eligibility Criteria
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)
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | 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 |
| Safety Issue: | |
| Description: | 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 Outcome Measures
| Measure: | 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 |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Evaluate incidents of adverse events during the time subjects are taking carvedilol with chemotherapy |
| Time Frame: | From Baseline to 30 days after stopping carvedilol. |
| Safety Issue: | |
| Description: | Evaluate adverse events during the time subjects are taking carvedilol with chemotherapy |
Details
| Phase: | Early Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | West Virginia University |
Last Updated
August 4, 2020
