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

ConditionsMedulloblastomaMedulloblastoma, ChildhoodMedulloblastoma Recurrent
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age1-25
SponsorSabine Mueller, MD, PhD

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

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.

Disqualifiers

For Cohort 1 only: participants who have previously been treated with BIT in combination. Treatment with individual bevacizumab, irinotecan or TMZ is not an exclusion criteria.

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.

Trial design

Design model

Sequential

Treatments tested in this trial

  • Liothyronine (L-T3)

    Drug

    Given orally (PO)

  • Bevacizumab

    Drug

    Given IV

  • Irinotecan

    Drug

    Given IV

  • Temozolomide (TMZ)

    Drug

    Given PO

Treatment groups

69 Participants
are divided into 3 treatment groups
Group A: Phase 1 Cohort (Cohort 1)Experimental treatment 4 interventions
Group B: Phase 2 Cohort 1- Relapsed/Progressive DiseaseExperimental treatment 4 interventions
Group C: Phase 2 Cohort 2 - cfDNA positive in CSFExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

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)

Time frame
Up to 28 days
2

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.

Time frame
Up to 28 days
3

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.

Time frame
Up to 28 days
4

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.

Time frame
up to 9 months

Secondary outcomes

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Sabine Mueller, MD, PhD

Lead sponsor

University of California, San Francisco

Sponsor institution

Source ClinicalTrials.gov
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