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

NCT03971734 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: ABTC 1804UM1CA137443
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

High Grade Glioma; Anaplastic Astrocytoma; Anaplastic Oligodendroglioma; Glioblastoma

Outcome Measures

Primary Outcomes (1)

• Dose of regadenoson

  Dose of regadenoson which results in an increase of gadolinium Ktrans by over 10 times.

  15 minutes

Study Arms (7)

Arm 1 regadenoson 0.05mg

EXPERIMENTAL

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

Drug: Regadenoson 0.05mg

Arm 2 regadenoson 0.1mg

EXPERIMENTAL

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.

Drug: Regadensoson 0.1mg

Arm 3 regadenoson 0.2mg

EXPERIMENTAL

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.

Drug: Regadensoson 0.2mg

Arm 4 regadenoson 0.4mg

EXPERIMENTAL

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.

Drug: Regadensoson 0.4mg

Arm 5 regadenoson 0.7mg

EXPERIMENTAL

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.

Drug: Regadensoson 0.7mg

Arm 6 regadenoson 1.0mg

EXPERIMENTAL

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.

Drug: Regadensoson 1.0mg

Arm 7 regadenoson 1.4mg

EXPERIMENTAL

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.

Drug: Regadensoson 1.4mg

Interventions

Regadenoson 0.05mg DRUG

Regadensoson 0.05mg administered prior to MRI

Arm 1 regadenoson 0.05mg

Regadensoson 0.1mg DRUG

Regadensoson 0.1mg administered prior to MRI

Arm 2 regadenoson 0.1mg

Regadensoson 0.2mg DRUG

Regadensoson 0.2mg administered prior to MRI

Arm 3 regadenoson 0.2mg

Regadensoson 0.4mg DRUG

Regadensoson 0.4mg administered prior to MRI

Arm 4 regadenoson 0.4mg

Regadensoson 0.7mg DRUG

Regadensoson 0.7mg administered prior to MRI

Arm 5 regadenoson 0.7mg

Regadensoson 1.0mg DRUG

Regadensoson 1.0mg administered prior to MRI

Arm 6 regadenoson 1.0mg

Regadensoson 1.4mg DRUG

Regadensoson 1.4mg administered prior to MRI

Arm 7 regadenoson 1.4mg

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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.
• Patients must have stable MRI (no progression of disease) for the past 2 months or more.
• Patients may have an unlimited number of prior relapses.
• The following intervals from previous treatments are required to be eligible:
• weeks from the completion of radiation.
• weeks from an anti-VEGF therapy
• weeks from a nitrosourea chemotherapy
• weeks from a non-nitrosourea chemotherapy
• weeks or 5 half-lives from any investigational (not FDA-approved) agents
• weeks from administration of a non-cytotoxic, FDA-approved agent (e.g., erlotinib, hydroxychloroquine, etc.)
• Age ≥18 years and ≤ 45 years.
• Karnofsky Performance (KPS) Status 80% (see Appendix A).
• Patients must have adequate organ and marrow function as defined below:
• \- Creatinine ≤ 1.5 mg/Dl or eGFR ≥30 mL/min/1.73 m2

You may not qualify if:

• 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.
• Patients who are receiving any other investigational agents.
• History of hypersensitivity reactions attributed to compounds of similar chemical or biologic composition to regadenoson.
• 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
• Patients who have uncontrolled hypo- or hypertension defined as a systolic blood pressure \<90 mmHg or \>180 mmHg, respectively.
• Patients who have uncontrolled asthma or seizures.
• Patients taking potential neurotoxic medications - see eligibility criteria of protocol for specific list of medications
• Patients with uncontrolled concurrent illness.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157-1096, United States

Location

Related Publications (1)

• Grossman SA, Romo CG, Ye X, Kral B, Strowd RE, Lesser G, Raymond C, Iacoboni M, Desideri S, Fisher J, Danda N, Ellingson BM. Assessing the dose of regadenoson required to transiently alter blood-brain barrier integrity in patients with infiltrating gliomas. Neurooncol Adv. 2025 Feb 15;7(1):vdaf041. doi: 10.1093/noajnl/vdaf041. eCollection 2025 Jan-Dec.

  PMID: 40225909 DERIVED

MeSH Terms

Conditions

Glioma; Astrocytoma; Oligodendroglioma; Glioblastoma

Interventions

regadenoson

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Stuart A Grossman, MD

  ABTC

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Seven dose levels of Regadenoson will be studied in part 1, minimum 3 patients per dose level. Part 2 will include 5 patients at each level that achieved thresh hold in part 1

Study Record Dates

• First Submitted: May 31, 2019
• First Posted: June 3, 2019
• Study Start: December 6, 2019
• Primary Completion: April 30, 2022
• Study Completion: October 2, 2023
• Last Updated: October 6, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)