CompletedPhase 1

Evaluation of LY2606368 Therapy in Combination With Cyclophosphamide or Gemcitabine for Children and Adolescents With Refractory or Recurrent Group 3/Group 4 or SHH Medulloblastoma Brain Tumors

United States21 participantsStarted 2019-08-08

Plain-language summary

SJELIOT is a phase 1 trial that aims to explore the combination of prexasertib with established DNA-damaging agents used in medulloblastoma to evaluate tolerance and pharmacokinetics in recurrent or refractory disease. Additionally, a small expansion cohort will be incorporated into the trial at the combination MTD/RP2D (maximum tolerated dose/recommended phase two dose) to detect a preliminary efficacy signal. Stratum A: Prexasertib and Cyclophosphamide Primary Objectives * To determine the safety and tolerability and estimate the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of combination treatment with prexasertib and cyclophosphamide in participants with recurrent/refractory Group 3 and Group 4 medulloblastoma and recurrent/refractory sonic hedgehog (SHH) medulloblastoma. * To characterize the pharmacokinetics of prexasertib in combination with cyclophosphamide. Secondary Objectives * To estimate the rate and duration of objective response and progression free survival (PFS) associated with prexasertib and cyclophosphamide treatment in this patient population. * To characterize the pharmacokinetics of cyclophosphamide and metabolites. Stratum B: Prexasertib and Gemcitabine Primary Objectives * To determine the safety and tolerability and estimate the MTD/RP2D of combination treatment with prexasertib and gemcitabine in participants with recurrent/refractory Group 3 and Group 4 medulloblastoma. * To characterize the pharmacokinetics of prexasertib in combination with gemcitabine. Secondary Objectives * To estimate the rate and duration of objective response and PFS associated with prexasertib and gemcitabine treatment in this patient population. * To characterize the pharmacokinetics of gemcitabine and gemcitabine triphosphate (only at St. Jude Children's Research Hospital).

Who can participate

Age range

1 Year – 24 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.

Inclusion Criteria: Screening Phase * Participants with recurrent, refractory, or progressive medulloblastoma. * Age ≥ 1 year and \< 25 years at the time of screening. * Participants and/or guardian can understand and is willing to sign a written informed consent document according to institutional guidelines. Exclusion Criteria: Screening Phase * Previous exposure to any CHK1 inhibitor. * 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 \> 480 msec). Inclusion Criteria: Strata A and B * Participant must be ≥1 year and \<25 years of age at time of screening. * Participant must have recurrent, progressive or refractory Group 3/Group 4 or SHH medulloblastoma (per central pathology confirmation of primary tissue and/or relapsed tissue). Central pathology review previously completed at St. Jude Children's Research Hospital using equivalent methods can be used for enrollment. Note: Group 3/Group 4 may be referred to as Non-WNT Non-SHH (NWNS) in pathology reports. Medulloblastoma patients with indeterminate molecular subgroup after central pathology review are eligible for enrollment on stratum A. * Participant must have measurable or evaluable disease as defined in the protocol. * Participant must have received their last dose of myelosuppressive anticancer chemotherapy at least 3 weeks prior to study enrollment. * Participants must h…

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 prexasertib and cyclophosphamide or gemcitabine treatment

To determine the safety and tolerability of combination treatment with prexasertib and cyclophosphamide or gemcitabine.

Timeframe: Up to 2 years after start of prexasertib and cyclophosphamide or gemcitabine treatment

To characterize the area under the concentration-time curve (AUC0-∞) of prexasertib in combination with cyclophosphamide or gemcitabine.

Timeframe: prexasertib and cyclophosphamide or gemcitabine treatment course 1 days 2 through 7

To characterize the systemic clearance (CL) of prexasertib in combination with cyclophosphamide or gemcitabine.

Timeframe: prexasertib and cyclophosphamide or gemcitabine treatment course 1 days 2 through 7

Trial details

NCT IDNCT04023669

SponsorSt. Jude Children's Research Hospital

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2023-05-01

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