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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

Primary Purpose

Brain Tumor, Brain Tumor, Recurrent, Brain Tumor, Refractory

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Prexasertib
Cyclophosphamide
Gemcitabine
filgrastim
peg-filgrastim
Sponsored by
St. Jude Children's Research Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain Tumor focused on measuring Brain Tumors in Adolescents, Brain Tumors in Children, Brain Tumors in Young Adults, CHK1/2 Inhibitor, Combination therapy, Indeterminate molecular subgroup, Medulloblastoma, Group 3, Medulloblastoma, Group 4, Medulloblastoma, G3/G4, Progressive brain tumor, Recurrent brain tumor, Refractory brain tumor, Sonic hedgehog, SHH Medulloblastoma, St. Jude Brain Tumor Studies, St. Jude Studies, St. Jude Treatment, Molecular, Molecular therapy

Eligibility Criteria

1 Year - 24 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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 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.

Exclusion Criteria: Strata A and B

  • Participant who is receiving any other investigational agents.
  • Participants with other clinically significant medical disorders (i.e. serious infections or significant cardiac, pulmonary, hepatic, psychiatric, or other organ dysfunction) that could compromise their ability to tolerate protocol therapy or would interfere with the study procedures or results.
  • Participant with a history of clinically significant, uncontrolled heart disease and/or repolarization abnormalities as documented by a standard 12-lead ECG.
  • Shortening fraction of <27% by ECHO or ejection fraction of <50% by gated radionuclide study.
  • Prior history of QTc prolongation or QTc interval of > 480 msec.
  • Female participants who are breastfeeding a child.
  • Participants are excluded if unable to comply with guidelines listed in appendix I.

Sites / Locations

  • St. Jude Children's Research Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

A: prexasertib + cyclophosphamide

B: prexasertib + gemcitabine

Arm Description

Stratum A: Participants receive combination treatment with cyclophosphamide given intravenously (IV) on days 1 and 15 and prexasertib given intravenously (IV) on days 2 and 16. Cycles repeat every 28 days for up to 24 months (26 cycles) in the absence of disease progression or unacceptable toxicity. They may also receive growth therapy support with filgrastim or peg-filgrastim. Note: Only if absolutely necessary, cyclophosphamide may be given on day 16 and prexasertib may be given on day 17.

Stratum B: Participants receive combination treatment with gemcitabine given intravenously (IV) on days 1 and 15 and prexasertib given intravenously (IV) on days 2 and 16. Cycles repeat every 28 days for up to 24 months (26 cycles) in the absence of disease progression or unacceptable toxicity. They may also receive growth therapy support with filgrastim or peg-filgrastim. Note: Only if absolutely necessary, gemcitabine may be given on day 16 and prexasertib may be given on day 17.

Outcomes

Primary Outcome Measures

Estimate the Maximum tolerated dose (MTD)/Recommended Phase 2 Dose (RP2D) of each doublet by stratum
The maximum tolerated dose (MTD) is empirically defined as the highest dose level at which six patients have been treated with at most one patient experiencing a dose-limiting toxicity (DLT) and the next higher dose level has been determined to be too toxic. The MTD estimate will not be available if the lowest dose level studied is too toxic or the highest dose level studied is considered safe. In the latter case, the highest studied safe dose may be considered as the recommended phase 2 dose (RP2D). The MTD estimation will be limited to evaluable patients and toxicity assessments from course 1 (28 days).
To determine the safety and tolerability of combination treatment with prexasertib and cyclophosphamide or gemcitabine.
Incidence of adverse event data at least possibly related to treatment will be summarized in tables by treatment combination and by dose level.
To characterize the area under the concentration-time curve (AUC0-∞) of prexasertib in combination with cyclophosphamide or gemcitabine.
Prexasertib area under the curve (AUC0-∞) is estimated based on course 1, days 2 through 7 PK samples.
To characterize the systemic clearance (CL) of prexasertib in combination with cyclophosphamide or gemcitabine.
Prexasertib systemic clearance (CL) is estimated based on course 1, days 2 through 7 pharmacokinetic samples.

Secondary Outcome Measures

Rate of objective response (complete or partial response) by stratum
The incidence of objective responses (complete or partial response) observed during prexasertib and cyclophosphamide or gemcitabine treatment or during follow-up prior to progression or initiation of alternative cancer therapy.
Duration of objective response by stratum
The duration of objective response is measured from the time the measurement criteria are met for complete response (CR) or partial response (PR), whichever is recorded first, until the first day on which recurrent or progressive disease is objectively documented.
Progression-free survival for patients treated with prexasertib and cyclophosphamide or gemcitabine
Progression-free survival (PFS) is defined from the time of treatment initiation until disease progression or until death from any cause (whichever is earlier) for patients who experience an event and until the date of last follow-up for those who are alive and progression free at the time of analysis. PFS is estimated by Kaplan-Meier approach and median PFS is reported.
To characterize the area under the concentration-time curve (AUC0-24h) of cyclophosphamide.
Cyclophosphamide area under the curve (AUC0-24h) is estimated based on course 1, days 1 and 2 PK samples.
To characterize the systemic clearance (CL) of cyclophosphamide.
Cyclophosphamide systemic clearance (CL) is estimated based on course 1, days 1 and 2 PK samples.
To characterize the area under the concentration-time curve (AUC0-24h) of 4-hydroxy-cyclophosphamide.
4-hydroxy-cyclophosphamide are under the curve AUC0-24h is estimated based on course 1, days 1 and 2 PK samples.
To characterize the area under the concentration-time curve (AUC0-24h) of carboxyethylphosphoramide mustard.
Carboxyethylphosphoramide mustard area under the curve (AUC0-24h) is estimated based on course 1, days 1 and 2. PK samples.
To characterize the area under the concentration-time curve (AUC0-4h) of gemcitabine.
Gemcitabine area under the curve (AUC0-4h) is estimated based on course 1, day 1 PK samples.
To characterize the systemic clearance (CL) of gemcitabine.
Gemcitabine systemic clearance (CL) is estimated based on course 1, day 1 PK samples.
To characterize the area under the concentration-time curve (AUC0-4h) of gemcitabine triphosphate (only at St. Jude Children's Research Hospital).
Gemcitabine triphosphate are under the curve AUC0-4h is estimated based on course 1, day 1 PK samples.

Full Information

First Posted
July 11, 2019
Last Updated
May 8, 2023
Sponsor
St. Jude Children's Research Hospital
Collaborators
Eli Lilly and Company
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1. Study Identification

Unique Protocol Identification Number
NCT04023669
Brief Title
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
Official Title
St. Jude ELIOT: Phase 1 Evaluation of LY2606368, a Molecularly-Targeted CHK1/2 Inhibitor Therapy, in Combination With Cyclophosphamide or Gemcitabine for Children and Adolescents With Refractory or Recurrent Group 3/Group 4 or SHH Medulloblastoma Brain Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 8, 2019 (Actual)
Primary Completion Date
May 1, 2023 (Actual)
Study Completion Date
April 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
St. Jude Children's Research Hospital
Collaborators
Eli Lilly and Company

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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 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).
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 population: Participants with recurrent/refractory Group 3 and Group 4 (G3/G4) medulloblastoma, recurrent/refractory sonic hedgehog (SHH) medulloblastoma and medulloblastoma participants with Indeterminate molecular subgroup STRATUM B Combination Treatment: prexasertib and gemcitabine Patient population: Participants with recurrent/refractory Group 3 and Group 4 medulloblastoma Participants with a diagnosis of G3/G4 medulloblastoma who qualify for both treatment strata will be assigned per slot availability as well as institutional PI preference. If slots are available in both stratum A and stratum B, patients will be assigned to the dose level nearest completion. The Rolling 6 design will be used separately in each stratum to estimate the maximum tolerated dose (MTD) or recommended phase two dose (RP2D). Therapy will be administered in cycles of 28 days and may be continued for up to 24 months (26 cycles) in the absence of disease progression or unacceptable toxicity. Participants will receive doublet therapy in cycles of 28 days. The dose-limiting toxicity (DLT)-evaluation period will consist of the first cycle until day 1 criteria of cycle 2 has been met. Participants will be evaluated at least once a week during the DLT-evaluation period and at regular intervals thereafter. Standard tests (i.e. physical exams, blood tests, and disease evaluations) will be undertaken at regular intervals. Research-associated evaluations (i.e. pharmacokinetic studies, etc.) will also be carried out during therapy. Treatment may be continued for up to 2 years in the absence of disease progression or unacceptable toxicity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
Keywords
Brain Tumors in Adolescents, Brain Tumors in Children, Brain Tumors in Young Adults, CHK1/2 Inhibitor, Combination therapy, Indeterminate molecular subgroup, Medulloblastoma, Group 3, Medulloblastoma, Group 4, Medulloblastoma, G3/G4, Progressive brain tumor, Recurrent brain tumor, Refractory brain tumor, Sonic hedgehog, SHH Medulloblastoma, St. Jude Brain Tumor Studies, St. Jude Studies, St. Jude Treatment, Molecular, Molecular therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A: prexasertib + cyclophosphamide
Arm Type
Experimental
Arm Description
Stratum A: Participants receive combination treatment with cyclophosphamide given intravenously (IV) on days 1 and 15 and prexasertib given intravenously (IV) on days 2 and 16. Cycles repeat every 28 days for up to 24 months (26 cycles) in the absence of disease progression or unacceptable toxicity. They may also receive growth therapy support with filgrastim or peg-filgrastim. Note: Only if absolutely necessary, cyclophosphamide may be given on day 16 and prexasertib may be given on day 17.
Arm Title
B: prexasertib + gemcitabine
Arm Type
Experimental
Arm Description
Stratum B: Participants receive combination treatment with gemcitabine given intravenously (IV) on days 1 and 15 and prexasertib given intravenously (IV) on days 2 and 16. Cycles repeat every 28 days for up to 24 months (26 cycles) in the absence of disease progression or unacceptable toxicity. They may also receive growth therapy support with filgrastim or peg-filgrastim. Note: Only if absolutely necessary, gemcitabine may be given on day 16 and prexasertib may be given on day 17.
Intervention Type
Drug
Intervention Name(s)
Prexasertib
Other Intervention Name(s)
LY2606368
Intervention Description
IV
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan
Intervention Description
IV
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Other Intervention Name(s)
2'-deoxy-2',2' difluorocytidine monohydrochloride, LY18801, Gemzar®
Intervention Description
IV
Intervention Type
Biological
Intervention Name(s)
filgrastim
Other Intervention Name(s)
G-CSF
Intervention Description
Given subcutaneously (SQ). Alternatively, pegfilgrastim may be given.
Intervention Type
Biological
Intervention Name(s)
peg-filgrastim
Other Intervention Name(s)
pegylated filgrastim, PEG filgrastim, Neulasta®
Intervention Description
Given subcutaneously (SQ). Alternatively, filgrastim may be given.
Primary Outcome Measure Information:
Title
Estimate the Maximum tolerated dose (MTD)/Recommended Phase 2 Dose (RP2D) of each doublet by stratum
Description
The maximum tolerated dose (MTD) is empirically defined as the highest dose level at which six patients have been treated with at most one patient experiencing a dose-limiting toxicity (DLT) and the next higher dose level has been determined to be too toxic. The MTD estimate will not be available if the lowest dose level studied is too toxic or the highest dose level studied is considered safe. In the latter case, the highest studied safe dose may be considered as the recommended phase 2 dose (RP2D). The MTD estimation will be limited to evaluable patients and toxicity assessments from course 1 (28 days).
Time Frame
1 month after start of prexasertib and cyclophosphamide or gemcitabine treatment
Title
To determine the safety and tolerability of combination treatment with prexasertib and cyclophosphamide or gemcitabine.
Description
Incidence of adverse event data at least possibly related to treatment will be summarized in tables by treatment combination and by dose level.
Time Frame
Up to 2 years after start of prexasertib and cyclophosphamide or gemcitabine treatment
Title
To characterize the area under the concentration-time curve (AUC0-∞) of prexasertib in combination with cyclophosphamide or gemcitabine.
Description
Prexasertib area under the curve (AUC0-∞) is estimated based on course 1, days 2 through 7 PK samples.
Time Frame
prexasertib and cyclophosphamide or gemcitabine treatment course 1 days 2 through 7
Title
To characterize the systemic clearance (CL) of prexasertib in combination with cyclophosphamide or gemcitabine.
Description
Prexasertib systemic clearance (CL) is estimated based on course 1, days 2 through 7 pharmacokinetic samples.
Time Frame
prexasertib and cyclophosphamide or gemcitabine treatment course 1 days 2 through 7
Secondary Outcome Measure Information:
Title
Rate of objective response (complete or partial response) by stratum
Description
The incidence of objective responses (complete or partial response) observed during prexasertib and cyclophosphamide or gemcitabine treatment or during follow-up prior to progression or initiation of alternative cancer therapy.
Time Frame
Up to 1 year after completion of prexasertib and cyclophosphamide or gemcitabine treatment
Title
Duration of objective response by stratum
Description
The duration of objective response is measured from the time the measurement criteria are met for complete response (CR) or partial response (PR), whichever is recorded first, until the first day on which recurrent or progressive disease is objectively documented.
Time Frame
Up to 1 year after completion of prexasertib and cyclophosphamide or gemcitabine treatment
Title
Progression-free survival for patients treated with prexasertib and cyclophosphamide or gemcitabine
Description
Progression-free survival (PFS) is defined from the time of treatment initiation until disease progression or until death from any cause (whichever is earlier) for patients who experience an event and until the date of last follow-up for those who are alive and progression free at the time of analysis. PFS is estimated by Kaplan-Meier approach and median PFS is reported.
Time Frame
Up to 3 years from diagnosis
Title
To characterize the area under the concentration-time curve (AUC0-24h) of cyclophosphamide.
Description
Cyclophosphamide area under the curve (AUC0-24h) is estimated based on course 1, days 1 and 2 PK samples.
Time Frame
prexasertib and cyclophosphamide treatment course 1, days 1 and 2
Title
To characterize the systemic clearance (CL) of cyclophosphamide.
Description
Cyclophosphamide systemic clearance (CL) is estimated based on course 1, days 1 and 2 PK samples.
Time Frame
prexasertib and cyclophosphamide treatment course 1, days 1 and 2
Title
To characterize the area under the concentration-time curve (AUC0-24h) of 4-hydroxy-cyclophosphamide.
Description
4-hydroxy-cyclophosphamide are under the curve AUC0-24h is estimated based on course 1, days 1 and 2 PK samples.
Time Frame
prexasertib and cyclophosphamide treatment course 1, days 1 and 2
Title
To characterize the area under the concentration-time curve (AUC0-24h) of carboxyethylphosphoramide mustard.
Description
Carboxyethylphosphoramide mustard area under the curve (AUC0-24h) is estimated based on course 1, days 1 and 2. PK samples.
Time Frame
prexasertib and cyclophosphamide treatment course 1, days 1 and 2
Title
To characterize the area under the concentration-time curve (AUC0-4h) of gemcitabine.
Description
Gemcitabine area under the curve (AUC0-4h) is estimated based on course 1, day 1 PK samples.
Time Frame
prexasertib and gemcitabine treatment course 1, day 1.
Title
To characterize the systemic clearance (CL) of gemcitabine.
Description
Gemcitabine systemic clearance (CL) is estimated based on course 1, day 1 PK samples.
Time Frame
prexasertib and cyclophosphamide treatment course 1, day 1
Title
To characterize the area under the concentration-time curve (AUC0-4h) of gemcitabine triphosphate (only at St. Jude Children's Research Hospital).
Description
Gemcitabine triphosphate are under the curve AUC0-4h is estimated based on course 1, day 1 PK samples.
Time Frame
prexasertib and cyclophosphamide treatment course 1, day 1

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
24 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 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. Exclusion Criteria: Strata A and B Participant who is receiving any other investigational agents. Participants with other clinically significant medical disorders (i.e. serious infections or significant cardiac, pulmonary, hepatic, psychiatric, or other organ dysfunction) that could compromise their ability to tolerate protocol therapy or would interfere with the study procedures or results. Participant with a history of clinically significant, uncontrolled heart disease and/or repolarization abnormalities as documented by a standard 12-lead ECG. Shortening fraction of <27% by ECHO or ejection fraction of <50% by gated radionuclide study. Prior history of QTc prolongation or QTc interval of > 480 msec. Female participants who are breastfeeding a child. Participants are excluded if unable to comply with guidelines listed in appendix I.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Giles W. Robinson, MD
Organizational Affiliation
St. Jude Children's Research Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
St. Jude Children's Research Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.
IPD Sharing Time Frame
Data will be made available at the time of article publication.
IPD Sharing Access Criteria
Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.
Links:
URL
http://www.stjude.org
Description
St. Jude Children's Research Hospital
URL
http://www.stjude.org/protocols
Description
Clinical Trials Open at St. Jude
URL
http://www.stjude.org/research/clinical-trials.html#c671955e2f6ffa4a5f9cd8cf39931465e1f28ef99042a579a1474aa7f29de3b5=2
Description
St. Jude Brain Tumor Studies

Learn more about this trial

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

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