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 range1 Year – 24 Years

SexALL

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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…

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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