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Determining Dose of Regadenoson Most Likely to Transiently Alter the Integrity of the Blood-Brain Barrier in Patients With High Grade Gliomas

Study Purpose

enroll patients with histologically confirmed high-grade gliomas to evaluate the ability of regadenoson to transiently disrupt a relatively intact blood-brain barrier (BBB). determine the best dose of regadenoson to disrupt the BBB and allow for enhanced penetration of gadolinium during MRI.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

 No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

 Interventional
Eligible Ages 18 Years - 45 Years
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria. 1. Patients must have histologically confirmed high grade glioma (including but not limited to glioblastoma (GBM), anaplastic astrocytoma (AA), gliosarcoma, and anaplastic oligodendroglioma). Patients with previous low-grade glioma who progressed after RT/chemotherapy and are biopsied and found to have GBM/GS are eligible. 2. Patients must have measurable contrast-enhancing disease by MRI imaging within 7-14 days of starting treatment (defined by at least 1 cm x 1 cm). Patient must be able to tolerate MRIs with contrast. 3. Patients must have stable MRI (no progression of disease) for the past 2 months or more. 4. Patients may have an unlimited number of prior relapses. 5. The following intervals from previous treatments are required to be eligible:

  • - 12 weeks from the completion of radiation.
  • - 16 weeks from an anti-VEGF therapy.
  • - 6 weeks from a nitrosourea chemotherapy.
  • - 3 weeks from a non-nitrosourea chemotherapy.
  • - 2 weeks or 5 half-lives from any investigational (not FDA-approved) agents.
  • - 2 weeks from administration of a non-cytotoxic, FDA-approved agent (e.g., erlotinib, hydroxychloroquine, etc.) 6.
Age ≥18 years and ≤ 45 years. 7. Karnofsky Performance (KPS) Status 80% (see Appendix A). 8. Patients must have adequate organ and marrow function as defined below:
  • - Creatinine ≤ 1.5 mg/Dl or eGFR ≥30 mL/min/1.73 m2.
9. Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. 10. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of regadenoson are eligible for this trial. 11. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria. 1. Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > Grade 1) with the exception of alopecia. 2. Patients who are receiving any other investigational agents. 3. History of hypersensitivity reactions attributed to compounds of similar chemical or biologic composition to regadenoson. 4. Patients with any history, current symptoms, or signs of cardiovascular disease including:
  • - any ischemic cardiac event (myocardial infarction, coronary revascularization, stable or unstable angina) - Ischemic or nonischemic cardiomyopathy and/or congestive heart failure.
  • - Supraventricular tachycardia, atrial fibrillation, and/or atrial flutter.
  • - Ventricular tachyarrhythmias.
  • - Severe sinus bradycardia defined as a resting heart rate <40 bpm.
  • - Symptomatic bradycardia, sick sinus syndrome, greater than first-degree AV block, left bundle branch block, and/or presence of a cardiac pacemaker.
  • - Stenotic valvular heart disease.
5. Patients who have uncontrolled hypo- or hypertension defined as a systolic blood pressure <90 mmHg or >180 mmHg, respectively. 6. Patients who have uncontrolled asthma or seizures. 7. Patients taking potential neurotoxic medications
  • - see eligibility criteria of protocol for specific list of medications.
8. Patients with uncontrolled concurrent illness. 9. Patients with psychiatric illness/social situations that would limit compliance with study requirements. 10. Pregnant women will be excluded from this study. 11. Because of the potential risk of serious cardiac reactions in the breastfed infant, advise the nursing mother to pump and discard breast milk for 10 hours after administration of regadenoson

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

 NCT03971734
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

 Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

 Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

 Stuart A Grossman, MD
Principal Investigator Affiliation ABTC
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

 Other, NIH
Overall Status Terminated
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

 High Grade Glioma, Anaplastic Astrocytoma, Anaplastic Oligodendroglioma, Glioblastoma
Additional Details

PRIMARY OBJECTIVE: To determine if there is a dose of regadenoson, in the range shown to be safe for clinical administration, that can increase gadolinium Ktrans by more than 10 times the values reported in the literature within normal-appearing brain parenchyma with a previously documented intact blood-brain barrier in patients with high grade gliomas. SECONDARY OBJECTIVE To determine if there is a dose of regadenoson, in the range shown to be safe for clinical administration, that can substantially alter the normalized, contrast enhanced MRI signal intensity in normal-appearing tissues and in: A) Brain adjacent to tumor (i.e. T2 hyperintense, but without contrast enhancement before regadenoson) and B) Contrast enhancing tumor (with contrast enhancement before regadenoson). Part I Treatment Plan.Part I of the protocol is designed to identify the best regadenoson dose(s) to transiently disrupt the blood-brain barrier as measured by DCE-MRI and contrast enhancement on T1-weighted images corresponding to an increase in the accumulation of MRI contrast (gadolinium) into normal appearing brain contralateral to the brain tumor. Patients who are at low risk of having complications with a standard regadenoson cardiac stress test (young with no known cardiac disease) and who have had stable MRI scans for at least 2 months prior to enrollment will be asked to undergo a research MRI within two weeks after their most recent previous MRI. Part II Treatment Plan.Part II will be initiated if the first portion of the study identifies one or more doses of regadenoson that meets the desired endpoint of a Ktrans value >0.04 min-1 within contralateral normal-appearing brain following regadenoson administration. Part II patients will undergo more extensive imaging prior to regadenoson administration to confirm that regadenoson has a significant effect on the BBB using a more comprehensive imaging approach. Five additional patients who are at low risk to have complications of a standard chemical cardiac stress test (young with no known significant cardiac disease) will be sequentially enrolled at each regadenoson dose meeting the desired endpoint in Part

  • I. In these cohorts, the full research imaging protocol will be utilized in both the pre- and post-regadenoson MRI scans which will allow a direct comparison of all imaging parameters in both the pre-regadenoson and post-regadenoson settings to be directly compared.

Arms & Interventions

Arms

Experimental: Arm 1 regadenoson 0.05mg

Approximately 10 minutes prior to undergoing the research MRI, patients will be administered a single dose of regadenoson at their assigned dose level, under the supervision of a cardiologist. The research MRI scan will be performed immediately following administration of regadenoson and appropriate monitoring of vital signs and 12-lead electrocardiography on a similar machine as the pre-enrollment eligibility MRI scan, using the same administered dose of gadolinium and acquisition parameters. The research MRI will consist of DCE perfusion MRI for estimation of Ktrans and will be performed with co-administration of standard doses of gadolinium following regadenoson dose. Regadenoson 0.05mg

Experimental: Arm 2 regadenoson 0.1mg

Approximately 10 minutes prior to undergoing the research MRI, patients will be administered a single dose of regadenoson at their assigned dose level, under the supervision of a cardiologist. The research MRI scan will be performed immediately following administration of regadenoson and appropriate monitoring of vital signs and 12-lead electrocardiography on a similar machine as the pre-enrollment eligibility MRI scan, using the same administered dose of gadolinium and acquisition parameters. The research MRI will consist of DCE perfusion MRI for estimation of Ktrans and will be performed with co-administration of standard doses of gadolinium following regadenoson dose.

Experimental: Arm 3 regadenoson 0.2mg

Approximately 10 minutes prior to undergoing the research MRI, patients will be administered a single dose of regadenoson at their assigned dose level, under the supervision of a cardiologist. The research MRI scan will be performed immediately following administration of regadenoson and appropriate monitoring of vital signs and 12-lead electrocardiography on a similar machine as the pre-enrollment eligibility MRI scan, using the same administered dose of gadolinium and acquisition parameters. The research MRI will consist of DCE perfusion MRI for estimation of Ktrans and will be performed with co-administration of standard doses of gadolinium following regadenoson dose.

Experimental: Arm 4 regadenoson 0.4mg

Approximately 10 minutes prior to undergoing the research MRI, patients will be administered a single dose of regadenoson at their assigned dose level, under the supervision of a cardiologist. The research MRI scan will be performed immediately following administration of regadenoson and appropriate monitoring of vital signs and 12-lead electrocardiography on a similar machine as the pre-enrollment eligibility MRI scan, using the same administered dose of gadolinium and acquisition parameters. The research MRI will consist of DCE perfusion MRI for estimation of Ktrans and will be performed with co-administration of standard doses of gadolinium following regadenoson dose.

Experimental: Arm 5 regadenoson 0.7mg

Approximately 10 minutes prior to undergoing the research MRI, patients will be administered a single dose of regadenoson at their assigned dose level, under the supervision of a cardiologist. The research MRI scan will be performed immediately following administration of regadenoson and appropriate monitoring of vital signs and 12-lead electrocardiography on a similar machine as the pre-enrollment eligibility MRI scan, using the same administered dose of gadolinium and acquisition parameters. The research MRI will consist of DCE perfusion MRI for estimation of Ktrans and will be performed with co-administration of standard doses of gadolinium following regadenoson dose.

Experimental: Arm 6 regadenoson 1.0mg

Approximately 10 minutes prior to undergoing the research MRI, patients will be administered a single dose of regadenoson at their assigned dose level, under the supervision of a cardiologist. The research MRI scan will be performed immediately following administration of regadenoson and appropriate monitoring of vital signs and 12-lead electrocardiography on a similar machine as the pre-enrollment eligibility MRI scan, using the same administered dose of gadolinium and acquisition parameters. The research MRI will consist of DCE perfusion MRI for estimation of Ktrans and will be performed with co-administration of standard doses of gadolinium following regadenoson dose.

Experimental: Arm 7 regadenoson 1.4mg

Approximately 10 minutes prior to undergoing the research MRI, patients will be administered a single dose of regadenoson at their assigned dose level, under the supervision of a cardiologist. The research MRI scan will be performed immediately following administration of regadenoson and appropriate monitoring of vital signs and 12-lead electrocardiography on a similar machine as the pre-enrollment eligibility MRI scan, using the same administered dose of gadolinium and acquisition parameters. The research MRI will consist of DCE perfusion MRI for estimation of Ktrans and will be performed with co-administration of standard doses of gadolinium following regadenoson dose.

Interventions

Drug: - Regadenoson 0.05mg

Regadensoson 0.05mg administered prior to MRI

Drug: - Regadensoson 0.1mg

Regadensoson 0.1mg administered prior to MRI

Drug: - Regadensoson 0.2mg

Regadensoson 0.2mg administered prior to MRI

Drug: - Regadensoson 0.4mg

Regadensoson 0.4mg administered prior to MRI

Drug: - Regadensoson 0.7mg

Regadensoson 0.7mg administered prior to MRI

Drug: - Regadensoson 1.0mg

Regadensoson 1.0mg administered prior to MRI

Drug: - Regadensoson 1.4mg

Regadensoson 1.4mg administered prior to MRI

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Baltimore, Maryland

Status

Address

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231

Winston-Salem, North Carolina

Status

Address

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157-1096

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