Status:

COMPLETED

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

Lead Sponsor:

St. Jude Children's Research Hospital

Collaborating Sponsors:

Eli Lilly and Company

Conditions:

Brain Tumor

Brain Tumor, Recurrent

Eligibility:

All Genders

1-24 years

Phase:

PHASE1

Brief 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 r...

Detailed Description

Participants will be stratified by the biological characteristics of their tumor to one of two treatment strata: STRATUM A * Combination Treatment: prexasertib and cyclophosphamide * Patient populat...

Eligibility Criteria

Inclusion

  • 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

  • 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 have had their last fraction of radiation (including CSI) at least 4 weeks prior to study enrollment. Participants who received radiation therapy for palliation must have had their last fraction of radiation at least 2 weeks prior to study enrollment.
  • \-- Note: Participants must have relapsed with recurrent, progressive or refractory disease after any prior radiation therapy that is not considered palliative. Palliative radiation therapy is defined as local small port RT to alleviate and/or palliate symptoms. (CSI, whole brain RT, large field/port RT, or large field/port multilevel spinal RT will not be considered palliative at any dose.)
  • Participant who are receiving corticosteroids must be on a stable or decreasing dose for at least 1 week prior to enrollment with no plans for escalation.
  • Participant must have a Lansky (≤ 16 years) or Karnofsky (\> 16 years) performance score of ≥50 and, in the opinion of the investigator, a minimum life expectancy of at least 6 weeks.
  • \-- Note: Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
  • Participant must have adequate bone marrow and organ function as defined as:
  • ANC ≥ 1.0 x 10\^9/L without growth factor support within 7 days
  • Platelet count ≥ 75x 10\^9/L without support of a platelet transfusion within 7 days
  • Hemoglobin ≥8.0 g/dL without support of a blood transfusion within 7 days
  • Potassium, total calcium (corrected for serum albumin), magnesium, sodium and phosphorus within institutional normal limits or corrected to within normal limits with supplements before first dose of study medication
  • Serum creatinine ≤ the maximum serum creatinine based on age/gender: Age: 1 to \< 2 years; maximum serum creatinine (mg/dL): 0.6 (male, female); Age: 2 to \< 6 years; maximum serum creatinine (mg/dL): 0.8 (male, female); Age: 6 to \< 10 years; maximum serum creatinine (mg/dL): 1 (male, female); Age: 10 to \< 13 years; maximum serum creatinine (mg/dL): 1.2 (male, female); Age: 13 to \< 16 years; maximum serum creatinine (mg/dL): 1.5 (male), 1.4 (female); Age :≥ 16 years; maximum serum creatinine (mg/dL): 1.7 (male), 1.4 (female).
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN. For the purposes of this study the ULN of ALT and AST is 45 U/L.
  • Total bilirubin ≤ ULN; or if \> ULN then direct bilirubin ≤ 1.5 x ULN
  • Female participants of childbearing age must have a negative pregnancy test at the time of enrollment.
  • Participants of childbearing or child fathering potential must be willing to use medically acceptable form of birth control during treatment and for 16 weeks after stopping treatment.
  • Participants and/or guardian have the ability to understand and the willingness to sign a written informed consent document according to institutional guidelines.

Key Trial Info

Start Date :

August 8 2019

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

January 13 2025

Estimated Enrollment :

21 Patients enrolled

Trial Details

Trial ID

NCT04023669

Start Date

August 8 2019

End Date

January 13 2025

Last Update

February 7 2025

Active Locations (1)

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St. Jude Children's Research Hospital

Memphis, Tennessee, United States, 38105