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

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

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.

Study Overview

• Status: Withdrawn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

Detailed Description

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.

• Study Type: Interventional
• 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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Carvedilol + Standard Treatment; 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; 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.; Other Names: Coreg

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: West Virginia University
• Collaborators: NovoCure Ltd.; West Virginia Clinical and Translational Science Institute

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2020
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): June 1, 2022

Study Registration Dates

• First Submitted: May 1, 2019
• First Submitted That Met QC Criteria: June 5, 2019
• First Posted (Actual): June 10, 2019

Study Record Updates

• Last Update Posted (Actual): April 12, 2021
• Last Update Submitted That Met QC Criteria: April 6, 2021
• Last Verified: April 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: WVU020318

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.: Yes