NCT04023669

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

Completed Phase 1 Last updated 7 February 2025

What this trial tests

Phase 1 trial testing Prexasertib in Brain Tumor in 21 participants. Completed in 13 January 2025.

Timeline

8 August 2019

Primary endpoint
1 May 2023

13 January 2025

Quick facts

Lead sponsor	St. Jude Children's Research Hospital
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	21
Start date	8 August 2019
Primary completion	1 May 2023
Estimated completion	13 January 2025
Sites	1 location across United States

Drugs / interventions tested

• Prexasertib
• Cyclophosphamide (cyclophosphamide) — full drug profile →
• Gemcitabine (gemcitabine) — full drug profile →
• filgrastim — full drug profile →
• peg-filgrastim — full drug profile →

Conditions studied

• Brain Tumor — all drugs for Brain Tumor →
• Brain Tumor, Recurrent — all drugs for Brain Tumor, Recurrent →
• Brain Tumor, Refractory — all drugs for Brain Tumor, Refractory →
• Brain Tumor, Pediatric — all drugs for Brain Tumor, Pediatric →

Sponsor

St. Jude Children's Research Hospital

Who can join

Adults 1 to 24, any sex, with Brain Tumor or Brain Tumor, Recurrent. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Leveraging the replication stress response to optimize cancer therapy.
   Cybulla E, Vindigni A. · · 2023 · cited 109× · PMID 36323800 · DOI 10.1038/s41568-022-00518-6
2. Targeting DNA repair pathway in cancer: Mechanisms and clinical application.
   Wang M, Chen S, Ao D. · · 2021 · cited 84× · PMID 34977872 · DOI 10.1002/mco2.103
3. Therapeutic Targeting of DNA Damage Response in Cancer.
   Choi W, Lee ES. · · 2022 · cited 61× · PMID 35163621 · DOI 10.3390/ijms23031701
4. Molecular stratifications, biomarker candidates and new therapeutic options in current medulloblastoma treatment approaches.
   Menyhárt O, Győrffy B. · · 2020 · cited 60× · PMID 31970590 · DOI 10.1007/s10555-020-09854-1
5. Targeting the DNA Damage Response to Overcome Cancer Drug Resistance in Glioblastoma.
   Ferri A, Stagni V, Barilà D. · · 2020 · cited 53× · PMID 32664581 · DOI 10.3390/ijms21144910
6. Modeling pediatric medulloblastoma.
   Roussel MF, Stripay JL. · · 2020 · cited 49× · PMID 31788908 · DOI 10.1111/bpa.12803
7. CHK1 protects oncogenic KRAS-expressing cells from DNA damage and is a target for pancreatic cancer treatment.
   Klomp JE, Lee YS, Goodwin CM, Papke B, et al · · 2021 · cited 41× · PMID 34852220 · DOI 10.1016/j.celrep.2021.110060
8. Small-molecule screen reveals synergy of cell cycle checkpoint kinase inhibitors with DNA-damaging chemotherapies in medulloblastoma.
   Endersby R, Whitehouse J, Pribnow A, Kuchibhotla M, et al · · 2021 · cited 40× · PMID 33472956 · DOI 10.1126/scitranslmed.aba7401