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

• Status: Recruiting
• Trial end date: 2022-03-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborator: National Cancer Institute (NCI)
• Treatments: Regadenoson

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