Liothyronine in Combination With BIT Regimen for Medulloblastoma With or Without Minimal Residual Disease

NCT07346157 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 250812NCI-2025-08554
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1/Phase 2 study assessing liothyronine (L-T3) immunotherapy and in combination with standard chemotherapy (bevacizumab, irinotecan and temozolomide (BIT)) in children and young adults with medulloblastoma that is relapsed or progressive after standard upfront therapy.

Conditions

Medulloblastoma; Medulloblastoma, Childhood; Medulloblastoma Recurrent

Outcome Measures

Primary Outcomes (5)

• Proportion of participants experienced an Adverse Event

  Proportion of participants with adverse events of L-T3 as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 5.0)

  Up to 28 days

• Proportion of participants who experience dose-limiting toxicity (DLT) (Dose Escalation)

  The DLT evaluable analysis set includes all participants in the dose-finding part of the study who have received the target doses of L-T3, and who have either experienced a DLT or were followed for the full DLT evaluation period. DLT is defined as L-T3-related toxicity at a frequency ≥33% in any treatment arm.

  Up to 28 days

• Maximum Tolerated Dose (MTD) (Dose Escalation)

  The DLT evaluable analysis set includes all participants in the dose-finding part of the study who have received the target doses of L-T3, and who have either experienced a DLT or were followed for the full DLT evaluation period. The MTD is defined as the dose level given for 14 days which ≤ 1/6 participants experience a DLT.

  Up to 28 days

• Percentage Progressive Free Survival (PFS) at month 9

  Cohort 1 Phase 2, PFS at 9 months is defined as the proportion of patients alive and progression-free 9 months from start of treatment. Any patient lost-to-follow-up prior to 9 months will be considered an event (i.e., progression/death) for the purposes of the analysis.

  up to 9 months

• Percentage of cf-DNA clearance

  Participants in Cohort 2 Phase 2 will be assessed in two serial measurements of at least one month apart to determine cf-DNA clearance in cerebrospinal fluid (CSF). Percentage of participants with cf-DNA clearance will be reported.

  Up to 30 days after last dose of L-T3.

Study Arms (3)

Phase 1 Cohort (Cohort 1)

EXPERIMENTAL

Participants will be treated with a backbone of BIT. L-T3 will be administered on day 1 of each cycle at planned dose levels (DL). Once the Recommended Phase 2 Dose (RP2D) is established with dosing days 1-7, an additional cohort of 6 participants will be treated at the maximum tolerated DL for 14 days of the cycle, Dose level escalation (DLE), which, if tolerated, will become the RP2D. If DLE is not tolerated, the RP2D will become the highest tolerated DL from the prior cohort.

Drug: Liothyronine (L-T3); Drug: Bevacizumab; Drug: Irinotecan; Drug: Temozolomide (TMZ)

Phase 2 Cohort 1- Relapsed/Progressive Disease

EXPERIMENTAL

Participants will be treated at the RP2D of L-T3 based on the results of the safety Phase 1 cohort. Participants may continue therapy for up to 12 cycles if there is no evidence of unacceptable toxicity, disease progression, or withdrawal of consent. For participants that are benefiting from therapy, they may continue L-T3 monotherapy for one additional year (24 cycles total therapy). Treatment beyond that specified in the protocol should be discussed with the study chairs. Duration of Follow up Participants will enter follow up after the 30-day toxicity period. Follow-up procedures are to be captured under the PNOC COMP protocol with the exception of protocol defined follow up procedures. Participants will be followed under the PNOC COMP protocol until death or withdrawal from study.

Drug: Liothyronine (L-T3); Drug: Bevacizumab; Drug: Irinotecan; Drug: Temozolomide (TMZ)

Phase 2 Cohort 2 - cfDNA positive in CSF

EXPERIMENTAL

Children and young adults with medulloblastoma and CSF cf-DNA positivity without radiographic disease progression/recurrence following standard upfront therapy. will include children and young adults with medulloblastoma and positive cf-DNA in CSF following initial standard therapy and will involve a Phase 2 to evaluate clearance of cf-DNA positive disease in CSF in response to L-T3 monotherapy at the RP2D. Cohort 2 will begin enrolling once the RP2D of L-T3 is established.

Drug: Liothyronine (L-T3)

Interventions

Liothyronine (L-T3) DRUG

Given orally (PO)

Also known as: L-T3

Phase 1 Cohort (Cohort 1); Phase 2 Cohort 1- Relapsed/Progressive Disease; Phase 2 Cohort 2 - cfDNA positive in CSF

Bevacizumab DRUG

Given IV

Also known as: vascular endothelial growth factor (VEGF) inhibitor, VEGF inhibitor

Phase 1 Cohort (Cohort 1); Phase 2 Cohort 1- Relapsed/Progressive Disease

Irinotecan DRUG

Given IV

Also known as: Camptosar

Phase 1 Cohort (Cohort 1); Phase 2 Cohort 1- Relapsed/Progressive Disease

Temozolomide (TMZ) DRUG

Given PO

Also known as: TMZ

Phase 1 Cohort (Cohort 1); Phase 2 Cohort 1- Relapsed/Progressive Disease

Eligibility Criteria

• Age: 1 Year - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Phase 1 and Phase 2, Cohort 1:
• Participants must have histologically confirmed medulloblastoma that is relapsed/progressive following standard upfront therapy. Tissue confirmation of medulloblastoma diagnosis is required at diagnosis and not required at the time of relapse for entry into the study.
• Phase 2, Cohort 2: Participants must have cerebrospinal fluid (CSF) with cell-free deoxyribonucleic acid (cf-DNA) + assessed in a Chemiluminescent immunoassay (CLIA)-certified or protocol-approved laboratory. After entry into the study, another CSF sample will be collected and analyzed centrally prior to initiation of protocol therapy to verify cf-DNA positivity.
• Evidence of Disease:
• Phase 1 and Phase 2, Cohort 1:
• Participants may have either Measurable or Evaluable Disease Measurable Disease: Participants must have clear residual disease at the time of enrollment, defined as tumor that is measurable in two perpendicular dimensions on MRI Evaluable Disease: Diffuse leptomeningeal disease OR clear MRI evidence of disease that may not be measurable in two perpendicular dimensions.
• Phase 2, Cohort 2:
• For cf-DNA positive cohort: Participants are not required to have measurable or evaluable disease but must have cf-DNA positivity in a CLIA-certified or protocol-approved laboratory, as above.
• Prior Therapy: Participants must have received standard upfront therapy for medulloblastoma (either with craniospinal radiation or high dose chemotherapy and autologous stem cell rescue. If other therapy utilized, must be discussed with study chairs prior to participation). Participants for Phase 1 and Phase 2 cohort 1 may have received further chemotherapy and/or radiation therapy beyond standard upfront therapy prior to trial enrollment. Participants within the Phase 2 cohort 1 must have experienced at least one, and at most, two relapses prior to study enrollment.
• Age 1-25 years old.
• Performance Score: Karnofsky ≥ 50 for participants \> 16 years of age and Lansky ≥ 50 for participants ≤16 years of age (See Appendix A). Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• For those participants currently treated with levothyroxine (Synthroid) they must have stable dosing for a minimum of 3 months prior to enrollment.
• Organ Function Requirements
• Peripheral absolute neutrophil count (ANC) ≥ 1000/cubic millimeters (mm3)
• Platelet count ≥ 75,000/microliter (uL) (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).

You may not qualify if:

• Participants who have had myelosuppressive chemotherapy within 3 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. (Participants receiving chemotherapy directly into the CSF at doses not expected to be myelosuppressive may have received therapy up to 7 days prior to enrollment).
• Participants must be at least 7 days since the completion of therapy with a biologic or small molecule agent or non-myelosuppressive chemotherapy agent. For any agent with known adverse events that can occur beyond 7 days after administration, the period prior to enrollment must be beyond the time during which adverse events are known to occur. Such participants should also be discussed with study chairs.
• Radiation: For participants on the Phase 1 and Phase 2 Cohort 1, the tumor designated as "measurable" for protocol purposes must not have received radiation within 6 weeks prior to study entry and focal radiation to areas of symptomatic metastatic disease must not be given within 14 days of study entry. If a new lesion occurs outside the radiation field, the participant is eligible to enroll at any time point from completion of radiation. For Cohort 2 participants, there is no required washout for radiation therapy.
• Participants who are receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to L-T3 or other agents used in study.
• Participants receiving any medications or substances that are strong inhibitors or strong inducers of CYP450 enzymes are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated list such as http://medicine.iupui.edu/clinpharm/ddis/table.aspx; medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the participant and/or legal parent or guardian will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection.
• Women of childbearing potential must not be pregnant or breast-feeding.
• Human immunodeficiency virus- (HIV) positive participants will be ineligible if HIV therapy regimen has not been stable for at least 4 weeks or there is intent to change the regimen within 8 weeks following enrollment, or if they are severely immunocompromised.
• Diagnosis of Graves' Disease or other pre-existing hyperthyroid disease.
• Participants with severe protein calorie malnutrition that in the opinion of the investigator may not tolerate protocol therapy.
• Participants with previous or active clinical cardiovascular disease, including the history of heart failure, myocardial infarction, cardiomyopathy, or ventricular systolic dysfunction on TTE (LVEF \<55% or SF \<28%), clinically significant arrhythmia (including atrial fibrillation, atrial flutter, frequent ventricular ectopy), clinically significant peripheral vascular disease.
• Participants with uncontrolled systemic hypertension (systolic blood pressure \> 95th percentile for age and height if participant is ≤ 17 years old)
• Participants with uncontrolled diabetes mellitus (HbA1c \>8%) or uncontrolled diabetes insipidus

Sponsors & Collaborators

• Sabine Mueller, MD, PhD: lead

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Medulloblastoma

Interventions

Triiodothyronine; Bevacizumab; Vascular Endothelial Growth Factor A; Irinotecan; Temozolomide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Thyronines; Thyroid Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Thyroxine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Vascular Endothelial Growth Factors; Angiogenic Proteins; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Camptothecin; Alkaloids; Heterocyclic Compounds; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Sabine Mueller

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kelly Hitchner

CONTACT

877-827-3222; PNOC044@ucsf.edu

Study Design

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

Study Record Dates

• First Submitted: January 14, 2026
• First Posted: January 16, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): March 31, 2031
• Study Completion (Estimated): March 31, 2031
• Last Updated: January 16, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF

Locations

US (1)