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

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).

Conditions

• Brain Tumor
• Brain Tumor, Recurrent
• Brain Tumor, Refractory
• Brain Tumor, Pediatric
• Medulloblastoma
• Medulloblastoma Recurrent
• Medulloblastoma, Non-WNT/Non-SHH
• Medulloblastoma, Non-WNT/Non-SHH, Group 3
• Medulloblastoma, Non-WNT/Non-SHH, Group 4
• Brain Cancer
• CNS Cancer
• CNS Tumor
• CNS Neoplasm

Interventions

DRUG

Prexasertib

IV

DRUG

Cyclophosphamide

IV

DRUG

Gemcitabine

IV

BIOLOGICAL

filgrastim

Given subcutaneously (SQ). Alternatively, pegfilgrastim may be given.

BIOLOGICAL

peg-filgrastim

Given subcutaneously (SQ). Alternatively, filgrastim may be given.

Sponsors & Collaborators

• Eli Lilly and Company

  collaborator INDUSTRY

• St. Jude Children's Research Hospital

  lead OTHER

Principal Investigators

• Giles W. Robinson, MD · St. Jude Children's Research Hospital

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

1 Year

Max Age

24 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-08-08

Primary Completion

2023-05-01

Completion

2025-01-13

FDA Drug

Yes

Countries

• United States

Study Locations