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

• ClinicalTrials.gov Identifier: NCT03861598
• Recruitment Status: Terminated
• First Posted: March 4, 2019
• Last Update Posted: September 24, 2021
• Sponsor: West Virginia University
• Collaborator: West Virginia Clinical and Translational Science Institute
• Information provided by (Responsible Party): West Virginia University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Glioblastoma Multiforme; Glioblastoma	Drug: Carvedilol	Early Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 4 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Feasibility Study: Evaluating Carvedilol With Chemotherapy in Second Line Glioblastoma Multiforme and Response of Peripheral Glioma Circulating Tumor Cells
• Actual Study Start Date: July 19, 2019
• Actual Primary Completion Date: August 21, 2020
• Actual Study Completion Date: June 17, 2021

Arms and Interventions

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; Coreg CR

Outcome Measures

Primary Outcome Measures :

1. 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 Outcome Measures :

1. 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.
2. 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

United States, West Virginia

WVU Cancer Institute - Mary Babb Randolph Cancer Center

Morgantown, West Virginia, United States, 26506

Sponsors and Collaborators

West Virginia University

West Virginia Clinical and Translational Science Institute

Investigators

• Principal Investigator: Joanna Kolodney, MD; West Virginia University

More Information

• Responsible Party: West Virginia University
• ClinicalTrials.gov Identifier: NCT03861598
• Other Study ID Numbers: WVU010318
• First Posted: March 4, 2019
• Last Update Posted: September 24, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

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