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Anti-metabolite

Combination Therapy for Brain Cancer

Phase 1

Waitlist Available

Led By Giles W. Robinson, MD

Research Sponsored by St. Jude Children's Research Hospital

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participants with recurrent, progressive, or refractory CNS tumors as confirmed through central pathology review and whose diagnosis is being treated on this study

Participants with recurrent, progressive, or refractory Non-WNT Non-SHH (NWNS) Medulloblastoma or Ependymoma as confirmed through central pathology review

Must not have

Participants with a history of clinically significant, uncontrolled heart disease and/or repolarization abnormalities

Previous exposure to a CDK4/6 inhibitor (palbociclib, abemaciclib, or ribociclib)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 month after start of therapy

Awards & highlights

No Placebo-Only Group

Summary

This trial will help improve cure rates for children with brain tumors by studying how the tumors continue to resist modern advances and by testing new approaches to treatment.

Who is the study for?

This trial is for children and young adults aged 1 to less than 25 years with recurrent brain tumors, except those with specific low-grade gliomas or retinal vein occlusion. Participants must have completed previous cancer treatments at least 4 weeks prior, be able to swallow medication (or use a g-tube), not be pregnant or breastfeeding, and agree to use effective contraception. They should also have stable health without serious medical issues that could affect the study.

What is being tested?

The SJDAWN trial tests combinations of drugs like Gemcitabine, Trametinib, Filgrastim, Sonidegib, and Ribociclib on various types of recurrent brain tumors in children and young adults. It aims to find safe dosages and see how well these drug pairs work together based on tumor type and molecular characteristics.

What are the potential side effects?

Potential side effects may include reactions related to the immune system's response to treatment, blood cell count changes leading to increased infection risk or bleeding problems, liver function changes causing fatigue or yellowing skin/eyes (jaundice), heart rhythm irregularities (QTc prolongation), as well as general discomforts such as nausea or rash.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My brain tumor is growing or returning despite treatment.

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My tumor is a specific type of brain cancer that has not responded to treatment.

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I am between 1 and 24 years old.

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I am not currently taking medications that strongly affect liver enzymes or that can alter my heart rhythm.

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I am not pregnant, can take a pregnancy test, and will use effective birth control during and 8 months after the study.

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My medulloblastoma is worsening or not responding to treatment, and my tumor has specific genetic changes.

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I can swallow pills.

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My weight and body surface area meet the trial's requirements.

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I am between 10 and 40 years old.

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I am between 1 and 24 years old.

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My brain tumor is growing or has come back despite treatment.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a history of serious heart disease that is not under control.

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I have been treated with a CDK4/6 inhibitor before.

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I am currently breastfeeding.

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I have been diagnosed with subependymoma or myxopapillary ependymoma.

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I have been treated with a MEK inhibitor before.

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I have been treated with a MEK inhibitor before.

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I have a confirmed RB1 gene mutation.

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I have been diagnosed with retinal vein occlusion.

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My condition is a recurring or worsening low grade brain tumor.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1 month after start of therapy

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~1 month after start of therapy

This trial's timeline: 3 weeks for screening, Varies for treatment, and 1 month after start of therapy for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Estimate the Maximum tolerated dose (MTD)/Recommended Phase 2 Dose (RP2D) of each doublet by stratum

Pharmacokinetics of combination treatment: Stratum A

Pharmacokinetics of combination treatment: Stratum B

+1 more

Secondary study objectives

Duration of objective response by stratum

Response rate by stratum

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Group I: C: ribociclib + sonidegibExperimental Treatment2 Interventions

Stratum C participants with refractory or recurrent medulloblastoma (SHH-activated) \>6 months off smoothened inhibitor, presence of 9q loss or PTCH1 mutant, skeletally mature. They received combination treatment with ribociclib and sonidegib. Stratum C is being closed due to low accrual

Group II: B: ribociclib + trametinibExperimental Treatment2 Interventions

Stratum B participants with a diagnosis of one of the following refractory or recurrent CNS diseases: medulloblastoma, \[sonic hedgehog (SHH)- or WNT-activated\];; high grade glioma (including: high grade glioma, (NOS), WHO Grade III or IV; anaplastic astrocytoma, IDH mutant; glioblastoma, IDH-wildtype; glioblastoma, IDH-mutant; diffuse midline glioma, H3K27-mutant; anaplastic oligodendroglioma, IDH mutant and 1p/19q-codeleted; anaplastic pleomorphic xanthoastrocytoma); select CNS embryonal tumors (including: embryonal tumors with multilayered rosettes, C19MC-altered; embryonal tumors with multilayered rosettes, NOS; medulloepithelioma; CNS neuroblastoma; CNS ganglioneuroblastoma; CNS embryonal tumor, NOS; atypical teratoid/rhabdoid tumor; CNS embryonal tumor with rhabdoid features). They receive combination treatment with ribociclib and trametinib. Stratum B has completed all the necessary accrual

Group III: A: ribociclib + gemcitabineExperimental Treatment3 Interventions

Stratum A participants with a diagnosis of refractory or recurrent medulloblastoma (Group 3/4) or refractory or recurrent ependymoma. (including: ependymoma, not otherwise specified (NOS), WHO Grade III; ependymoma, RELA fusion positive; anaplastic ependymoma; ependymoma, NOS, WHO grade II). They receive combination treatment with ribociclib and gemcitabine. They may also receive growth therapy support with filgrastim. Stratum A has completed all the necessary accrual

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Gemcitabine

2017

Completed Phase 3

~1920

filgrastim

1997

Completed Phase 3

~7260