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

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

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.

Study Overview

• Status: Terminated
• Conditions: Glioblastoma; Glioblastoma Multiforme
• Intervention / Treatment: Drug: Carvedilol

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.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • WVU Cancer Institute - Mary Babb Randolph Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	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.; Other Names: Coreg CR; Coreg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	Baseline, end of cycle 2, end of cycle 4, approximately 6 months depending on treatment plan

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate response with the addition of carvedilol to standard chemotherapy in the second line treatment in glioblastoma multiforme	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.	Baseline, end of cycle 2, end of cycle 4, approximately 6 months depending on treatment plan
Evaluate incidents of adverse events during the time subjects are taking carvedilol with chemotherapy	Evaluate adverse events during the time subjects are taking carvedilol with chemotherapy	From Baseline to 30 days after stopping carvedilol.

Collaborators and Investigators

• Sponsor: West Virginia University
• Collaborators: West Virginia Clinical and Translational Science Institute

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 19, 2019
• Primary Completion (ACTUAL): August 21, 2020
• Study Completion (ACTUAL): June 17, 2021

Study Registration Dates

• First Submitted: February 11, 2019
• First Submitted That Met QC Criteria: March 1, 2019
• First Posted (ACTUAL): March 4, 2019

Study Record Updates

• Last Update Posted (ACTUAL): September 24, 2021
• Last Update Submitted That Met QC Criteria: September 17, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplastic Processes; Neoplasm Metastasis; Glioblastoma; Neoplastic Cells, Circulating; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Protective Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Antioxidants; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Carvedilol
• Other Study ID Numbers: WVU010318

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No