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
Secondary Objectives
Stratum B: Prexasertib and Gemcitabine
Primary Objectives
Secondary Objectives
Condition or disease | Intervention/treatment | Phase |
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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 | Drug: Prexasertib Drug: Cyclophosphamide Drug: Gemcitabine Biological: filgrastim Biological: peg-filgrastim | Phase 1 |
Participants will be stratified by the biological characteristics of their tumor to one of two treatment strata:
STRATUM A
STRATUM B
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.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 100 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |
Actual Study Start Date : | August 8, 2019 |
Estimated Primary Completion Date : | June 2025 |
Estimated Study Completion Date : | June 2026 |
Arm | Intervention/treatment |
---|---|
Experimental: A: prexasertib + cyclophosphamide
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. |
Drug: Prexasertib
IV
Other Name: LY2606368
Drug: Cyclophosphamide IV
Other Name: Cytoxan
Biological: filgrastim Given subcutaneously (SQ). Alternatively, pegfilgrastim may be given.
Other Name: G-CSF
Biological: peg-filgrastim Given subcutaneously (SQ). Alternatively, filgrastim may be given.
Other Names:
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Experimental: B: prexasertib + gemcitabine
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. |
Drug: Prexasertib
IV
Other Name: LY2606368
Drug: Gemcitabine IV
Other Names:
Biological: filgrastim Given subcutaneously (SQ). Alternatively, pegfilgrastim may be given.
Other Name: G-CSF
Biological: peg-filgrastim Given subcutaneously (SQ). Alternatively, filgrastim may be given.
Other Names:
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Ages Eligible for Study: | 1 Year to 24 Years (Child, Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria: Screening Phase
Exclusion Criteria: Screening Phase
Inclusion Criteria: Strata A and B
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 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:
Exclusion Criteria: Strata A and B
Contact: Tabatha E. Doyle, RN | 901-595-2544 | tabatha.doyle@stjude.org |
United States, Tennessee | |
St. Jude Children's Research Hospital | Recruiting |
Memphis, Tennessee, United States, 38105 | |
Contact: Tabatha E. Doyle, RN 901-595-2544 tabatha.doyle@stjude.org | |
Principal Investigator: Giles W. Robinson, MD |
Principal Investigator: | Giles W. Robinson, MD | St. Jude Children's Research Hospital |
Tracking Information | |||||||||||||||
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First Submitted Date ICMJE | July 11, 2019 | ||||||||||||||
First Posted Date ICMJE | July 17, 2019 | ||||||||||||||
Last Update Posted Date | May 11, 2021 | ||||||||||||||
Actual Study Start Date ICMJE | August 8, 2019 | ||||||||||||||
Estimated Primary Completion Date | June 2025 (Final data collection date for primary outcome measure) | ||||||||||||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE | Same as current | ||||||||||||||
Change History | |||||||||||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures | Not Provided | ||||||||||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||||||||||
Descriptive Information | |||||||||||||||
Brief Title ICMJE | 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 ICMJE | 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 | ||||||||||||||
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
Secondary Objectives
Stratum B: Prexasertib and Gemcitabine Primary Objectives
Secondary Objectives
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Detailed Description |
Participants will be stratified by the biological characteristics of their tumor to one of two treatment strata: STRATUM A
STRATUM B
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. |
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Study Type ICMJE | Interventional | ||||||||||||||
Study Phase ICMJE | Phase 1 | ||||||||||||||
Study Design ICMJE | Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||||||||
Recruitment Status ICMJE | Recruiting | ||||||||||||||
Estimated Enrollment ICMJE |
100 | ||||||||||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||||||||||
Estimated Study Completion Date ICMJE | June 2026 | ||||||||||||||
Estimated Primary Completion Date | June 2025 (Final data collection date for primary outcome measure) | ||||||||||||||
Eligibility Criteria ICMJE |
Inclusion Criteria: Screening Phase
Exclusion Criteria: Screening Phase
Inclusion Criteria: Strata A and B
Exclusion Criteria: Strata A and B
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Sex/Gender ICMJE |
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Ages ICMJE | 1 Year to 24 Years (Child, Adult) | ||||||||||||||
Accepts Healthy Volunteers ICMJE | No | ||||||||||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | United States | ||||||||||||||
Removed Location Countries | |||||||||||||||
Administrative Information | |||||||||||||||
NCT Number ICMJE | NCT04023669 | ||||||||||||||
Other Study ID Numbers ICMJE | SJELIOT NCI-2019-04787 ( Registry Identifier: NCI Clinical Trial Registration Program ) |
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Has Data Monitoring Committee | No | ||||||||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | St. Jude Children's Research Hospital | ||||||||||||||
Study Sponsor ICMJE | St. Jude Children's Research Hospital | ||||||||||||||
Collaborators ICMJE | Eli Lilly and Company | ||||||||||||||
Investigators ICMJE |
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PRS Account | St. Jude Children's Research Hospital | ||||||||||||||
Verification Date | May 2021 | ||||||||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |