Digoxin Medulloblastoma Study

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/CLIAcertified assay (such as nanostring or methylation) performed on tissue fromdiagnosis or relapse.

• Patients must have received at least one prior course of chemotherapy for theirmedulloblastoma. They must also have received irradiation.

• Prior therapy: Therapy may not have been received more recently than the timeframesdefined below: Craniospinal radiotherapy: At least 3 months have elapsed since priorcraniospinal radiotherapy (at doses ≥ 18 Gy). Local radiotherapy: At least 3 monthssince prior local radiotherapy to primary tumor. Focal radiotherapy: At least 2weeks since prior focal radiotherapy to symptomatic metastatic sites.Myelosuppressive chemotherapy and/or immunotherapy and/or biologics: More than 3weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas),immunotherapy, or biologics. Hematopoietic growth factor: Seven days must haveelapsed since the completion of therapy with colony-stimulating factors (e.g.,filgrastim [G-CSF], sargramostim [GM-CSF], or erythropoietin), orplatelet-stimulating agents.

• Patients must have recovered from any surgical procedures such as biopsy, withneurological stability for > 7 days.

• Patients must have clear residual disease, defined as tumor that is measurable intwo perpendicular diameters on MRI (ie, largest tumor diameter and its largestperpendicular). The size of a measurable lesion at baseline should be at least 2times the thickness of the slices showing the tumor (adding the interslice gap).

• Patients must have a Lansky or Karnofsky performance status score of ≥ 50%. UseKarnofsky 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 beconsidered 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 screeningecho.

• Any patient that reports recent palpitations (within the last month), or concerningfindings on echo or ECG must be evaluated and cleared for treatment with digoxin bya cardiologist prior to enrollment. Study PI should be contacted for additionalquestions/concerns regarding these patients.

• Patients receiving concurrent dexamethasone are eligible, provided dosage is stableor 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 1of cycle 1, they should be reassessed for eligibility.

• Pregnancy: Females of childbearing potential must have a negative urine or serumpregnancy test prior to enrollment. Female patients who are lactating must agree tostop 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 andfor the duration of study participation. Should a woman become pregnant or suspectshe is pregnant while she or her partner is participating in this study, she shouldinform her treating physician immediately.

• All patients and/or their parents or legal guardians must have the ability tounderstand and the willingness to sign a written informed consent or assentdocument.

Exclusion Criteria:

• Participants who are receiving concurrent anticancer or any other investigationalagents are ineligible.

• Participants taking digoxin for any reason during treatment for initial diagnosis ofmedulloblastoma or relapse are ineligible. Exposure to digoxin therapy prior toinitial diagnosis of medulloblastoma is allowed.

• Patients with a history of allergic reactions attributed to compounds of similarchemical or biologic composition to digoxin are ineligible.

• Patients with serious or inadequately controlled cardiac arrhythmias, includingbaseline ectopy, ventricular tachycardia, frequent premature ventricularcontractions (PVCs), or symptomatic sinus bradycardia are excluded from the study.

• Patients taking medications that are known to interfere with digoxin metabolism areineligible.

• Participants with uncontrolled intercurrent illness, concurrent clinicallysignificant unrelated systemic illness (e.g. serious infection) or significantcardiac, pulmonary, hepatic, or other organ dysfunction that would compromise thepatient's ability to tolerate study treatment or would likely interfere with studyprocedures or results are ineligible.

• Participants with psychiatric illness/social situations that would limit compliancewith study requirements are ineligible.

• Pregnant women or women unwilling to stop breastfeeding are excluded from this studybecause it is unknown how pregnant women with recurrent medulloblastoma willmetabolize and tolerate digoxin. There is an unknown but potential risk for adverseevents in nursing infants secondary to treatment of the mother with digoxin in thissetting.

• Participants who in the opinion of the investigator may not be able to comply withthe safety monitoring requirements of the study.