Digoxin Medulloblastoma Study

Evaluation of Digoxin for Relapsed Non-WNT, Non-SHH Medulloblastoma

The purpose of this study is to evaluate the efficacy of digoxin in treating relapsed non-SHH, non-WNT medulloblastoma in pediatric and young adult patients.

Study Overview

• Status: Recruiting
• Conditions: Medulloblastoma; Medulloblastoma, Non-WNT/Non-SHH
• Intervention / Treatment: Drug: Digoxin

• Study Type: Interventional
• Enrollment (Estimated): 23
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jessica Crimella; Phone Number: 813-745-6250; Email: Jessica.Crimella@moffitt.org

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • University of Alabama at Birmingham Children's of Alabama
      • Principal Investigator: Laura Metrock, MD
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Recruiting
      • Arkansas Childrens Hospital
      • Principal Investigator: David Douglass, MD
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Not yet recruiting
      • Connecticut Children's Medical Center
      • Principal Investigator: Michael Isakoff, MD
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Not yet recruiting
      • Children's National Medical Center
      • Principal Investigator: Eugene Hwang, MD
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Not yet recruiting
      • Nemours Jacksonville
      • Principal Investigator: Darren Klawinski, MD
    • Miami, Florida, United States, 33136
      • Not yet recruiting
      • University of Miami
      • Principal Investigator: Bradley Gampel, MD
    • St. Petersburg, Florida, United States, 33701
      • Not yet recruiting
      • Johns Hopkins All Children's
      • Principal Investigator: Stacie Stapleton, MD
    • Tampa, Florida, United States, 33607
      • Recruiting
      • St. Joseph's Children's Hospital
      • Principal Investigator: Trisha Larkin, MD
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • Recruiting
      • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
      • Principal Investigator: Kenneth Cohen, MD
  • Missouri
    • St Louis, Missouri, United States, 63130
      • Recruiting
      • Washington University St. Louis
      • Principal Investigator: Mohamed Abdelbaki, MD
  • New York
    • The Bronx, New York, United States, 10467
      • Recruiting
      • Montefiore Medical Center
      • Principal Investigator: Alice Lee, MD
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Recruiting
      • UNC Lineberger Comprehensive Cancer Center
      • Principal Investigator: David Kram, MD
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Levine Cancer Institute
      • Principal Investigator: Erin Trovillion, MD
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University Medical Center
      • Principal Investigator: Scott Borinstein, MD
  • Texas
    • Dallas, Texas, United States, 75390
      • Not yet recruiting
      • UT Southwestern
      • Principal Investigator: Matthew Campbell, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must be age >12 months and <30 years at the time of enrollment.
• Patients must have relapsed non-WNT, non-SHH medulloblastoma confirmed by a CAP/CLIA certified assay (such as nanostring or methylation) performed on tissue from diagnosis or relapse.
• Patients must have received at least one prior course of chemotherapy for their medulloblastoma. They must also have received irradiation.
• Prior therapy: Therapy may not have been received more recently than the timeframes defined below: Craniospinal radiotherapy: At least 3 months have elapsed since prior craniospinal radiotherapy (at doses ≥ 18 Gy). Local radiotherapy: At least 3 months since prior local radiotherapy to primary tumor. Focal radiotherapy: At least 2 weeks since prior focal radiotherapy to symptomatic metastatic sites. Myelosuppressive chemotherapy and/or immunotherapy and/or biologics: More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas), immunotherapy, or biologics. Hematopoietic growth factor: Seven days must have elapsed since the completion of therapy with colony-stimulating factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], or erythropoietin), or platelet-stimulating agents.
• Patients must have recovered from any surgical procedures such as biopsy, with neurological stability for > 7 days.
• Patients must have clear residual disease, defined as tumor that is measurable in two perpendicular diameters on MRI (ie, largest tumor diameter and its largest perpendicular). The size of a measurable lesion at baseline should be at least 2 times the thickness of the slices showing the tumor (adding the interslice gap).
• Patients must have a Lansky or Karnofsky performance status score of ≥ 50%. Use Karnofsky for patients > 16 years of age and Lansky for patients < 16 years of age. Patients who are unable to ambulate but who are functional in a wheelchair will be considered ambulatory for the purpose of assessing the performance score.
• Patients must have normal organ and marrow function.
• Patient has no evidence of Wolff-Parkinson-White syndrome or high-grade AV block (form of second-degree heart block) on screening ECG.
• Patient has no evidence of hypertrophic obstructive cardiomyopathy on screening echo.
• Any patient that reports recent palpitations (within the last month), or concerning findings on echo or ECG must be evaluated and cleared for treatment with digoxin by a cardiologist prior to enrollment. Study PI should be contacted for additional questions/concerns regarding these patients.
• Patients receiving concurrent dexamethasone are eligible, provided dosage is stable or decreasing for ≥7 days prior to study enrollment.
• Patients must have a stable neurologic status for ≥7 days prior to study enrollment. If a patient experiences neurologic decline following enrollment but prior to day 1 of cycle 1, they should be reassessed for eligibility.
• Pregnancy: Females of childbearing potential must have a negative urine or serum pregnancy test prior to enrollment. Female patients who are lactating must agree to stop breastfeeding.
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
• All patients and/or their parents or legal guardians must have the ability to understand and the willingness to sign a written informed consent or assent document.

Exclusion Criteria:

• Participants who are receiving concurrent anticancer or any other investigational agents are ineligible.
• Participants taking digoxin for any reason during treatment for initial diagnosis of medulloblastoma or relapse are ineligible. Exposure to digoxin therapy prior to initial diagnosis of medulloblastoma is allowed.
• Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to digoxin are ineligible.
• Patients with serious or inadequately controlled cardiac arrhythmias, including baseline ectopy, ventricular tachycardia, frequent premature ventricular contractions (PVCs), or symptomatic sinus bradycardia are excluded from the study.
• Patients taking medications that are known to interfere with digoxin metabolism are ineligible.
• Participants with uncontrolled intercurrent illness, concurrent clinically significant unrelated systemic illness (e.g. serious infection) or significant cardiac, pulmonary, hepatic, or other organ dysfunction that would compromise the patient's ability to tolerate study treatment or would likely interfere with study procedures or results are ineligible.
• Participants with psychiatric illness/social situations that would limit compliance with study requirements are ineligible.
• Pregnant women or women unwilling to stop breastfeeding are excluded from this study because it is unknown how pregnant women with recurrent medulloblastoma will metabolize and tolerate digoxin. There is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with digoxin in this setting.
• Participants who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study.

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: Digoxin Treatment; Digoxin will be administered orally at a standard maintenance dosing. Each cycle will be 28 days.	Drug: Digoxin; 2.5-10 mcg/kg/day orally divided twice daily or once daily based on age on a continuous dosing schedule.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival at 4 months (PFS4)	Proportion of patients with progression free survival at 4 months after initiation of treatment.	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate	Response rate is defined as complete response (CR) + partial response (PR) at 4 months after initiation of study treatment.	4 months
Stable Disease (SD)	Stable disease rate as defined as stable disease (SD) at 4 months after initiation of study treatment.	4 months
Event Free Survival	Event Free Survival as defined as time from first dose of protocol therapy to secondary malignancy, death, or progression, whichever comes first.	Up to 12 months

Collaborators and Investigators

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborators: National Pediatric Cancer Foundation
• Investigators: Principal Investigator: Laura Metrock, MD, University of Alabama at Birmingham Children's of Alabama; Study Chair: Jonathan Metts, MD, Moffitt Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2026
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: November 20, 2024
• First Submitted That Met QC Criteria: November 20, 2024
• First Posted (Actual): November 22, 2024

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 25, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Medulloblastoma; Carbohydrates; Polycyclic Compounds; Glycosides; Steroids; Fused-Ring Compounds; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Digoxin
• Other Study ID Numbers: MCC-23221

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.: No