CompletedPhase 1

SJDAWN: St. Jude Children's Research Hospital Phase 1 Study Evaluating Molecularly-Driven Doublet Therapies for Children and Young Adults With Recurrent Brain Tumors

United States68 participantsStarted 2018-03-05

Plain-language summary

Approximately 90% of children with malignant brain tumors that have recurred or relapsed after receiving conventional therapy will die of disease. Despite this terrible and frustrating outcome, continued treatment of this population remains fundamental to improving cure rates. Studying this relapsed population will help unearth clues to why conventional therapy fails and how cancers continue to resist modern advances. Moreover, improvements in the treatment of this relapsed population will lead to improvements in upfront therapy and reduce the chance of relapse for all. Novel therapy and, more importantly, novel approaches are sorely needed. This trial proposes a new approach that evaluates rational combination therapies of novel agents based on tumor type and molecular characteristics of these diseases. The investigators hypothesize that the use of two predictably active drugs (a doublet) will increase the chance of clinical efficacy. The purpose of this trial is to perform a limited dose escalation study of multiple doublets to evaluate the safety and tolerability of these combinations followed by a small expansion cohort to detect preliminary efficacy. In addition, a more extensive and robust molecular analysis of all the participant samples will be performed as part of the trial such that we can refine the molecular classification and better inform on potential response to therapy. In this manner the tolerability of combinations can be evaluated on a small but relevant population and the chance of detecting antitumor activity is potentially increased. Furthermore, the goal of the complementary molecular characterization will be to eventually match the therapy with better predictive biomarkers. PRIMARY OBJECTIVES: * To determine the safety and tolerability and estimate the maximum tolerated dose/recommended phase 2 dose (MTD/RP2D) of combination treatment by stratum. * To characterize the pharmacokinetics of combination treatment by stratum. SECONDARY OBJECTIVE: * To estimate the rate and duration of objective response and progression free survival (PFS) by stratum.

Who can participate

Age range

1 Year – 39 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Potential participants will first be screened using the screening inclusion/exclusion shown below. If they meet the requirements of the screening phase, they will then be evaluated for enrollment based on the overall study's inclusion criteria as well as the stratum-specific inclusion/exclusion criteria for the applicable stratum, all of which are shown below. SCREENING INCLUSION CRITERIA - ALL PARTICIPANTS: * Participants with recurrent, progressive, or refractory brain tumors. * Age ≥ 1 year and \< 25 years at the time of screening. Exception: Participants with recurrent, progressive, or refractory Medulloblastoma and are ≥ 1 and \< 40 years of age at the time of study screening are eligible for screening. * Participants and/or guardian have the ability to understand and the willingness to sign a written informed consent document according to institutional guidelines. SCREENING EXCLUSION CRITERIA - ALL PARTICIPANTS: * Participants with a diagnosis of recurrent, progressive, or refractory low grade glioma (LGG). * Previous exposure to a CDK4/6 inhibitor (palbociclib, abemaciclib, or ribociclib). * Participants with a history of clinically significant, uncontrolled heart disease and/or repolarization abnormalities. * Participants with any history of QTc prolongation (i.e. QTc interval of \> 450 msec). Participants who meet the requirements of the screening phase will then be evaluated for enrollment based on the overall study's inclusion criteria as well as the stratum-s…

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

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

Timeframe: 1 month after start of therapy

Pharmacokinetics of combination treatment: Stratum A

Timeframe: Course 1: Days -1, 0, 1 and 15 and 16; Course 2: Day 1

Pharmacokinetics of combination treatment: Stratum B

Timeframe: Course 1: Days 1, 2, 3, 14 and 15

Pharmacokinetics of combination treatment: Stratum C

Timeframe: Course 1: Days -1, 0, 1, 2, 21, 22 and 28; Course 2: Day 1

Trial details

NCT IDNCT03434262

SponsorSt. Jude Children's Research Hospital

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2022-09-30

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