A Phase 1 interventional study of Prexasertib and Cyclophosphamide in Brain Tumor, Brain Tumor, Recurrent and Brain Tumor, Refractory, sponsored by St. Jude Children's Research Hospital. Completed at 1 site in United States. Open to participants aged 1 Year to 24 Years. Per ClinicalTrials.gov, last updated 2025-02-07.
Sponsored by St. Jude Children's Research Hospital · Phase 1, Interventional, and Treatment
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
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.
9,359 studies on the registry are indexed under Neoplasms; 2,486 are open to participants now.
This study's enrollment of 21 is below the median of 50 across 7,250 interventional studies indexed under Neoplasms.
Browse Neoplasms studies →St. Jude Children's Research Hospital is the lead sponsor of 434 studies on the registry; 99 are open to participants now.
Of its 60 completed or terminated interventional studies of FDA-regulated products, 35 (58%) have results posted.
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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
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 · Drug: Cyclophosphamide · Biological: filgrastim · Biological: peg-filgrastim
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 · Drug: Gemcitabine · Biological: filgrastim · Biological: peg-filgrastim
IV
Also known as: LY2606368
IV
Also known as: Cytoxan
IV
Also known as: 2'-deoxy-2',2' difluorocytidine monohydrochloride, LY18801, Gemzar®
Given subcutaneously (SQ). Alternatively, pegfilgrastim may be given.
Also known as: G-CSF
Given subcutaneously (SQ). Alternatively, filgrastim may be given.
Also known as: pegylated filgrastim, PEG filgrastim, Neulasta®
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).
Time frame: 1 month after start of prexasertib and cyclophosphamide or gemcitabine treatment
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.
Time frame: Up to 2 years after start of prexasertib and cyclophosphamide or gemcitabine treatment
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.
Time frame: prexasertib and cyclophosphamide or gemcitabine treatment course 1 days 2 through 7
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.
Time frame: prexasertib and cyclophosphamide or gemcitabine treatment course 1 days 2 through 7
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.
Time frame: Up to 1 year after completion of prexasertib and cyclophosphamide or gemcitabine treatment
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.
Time frame: Up to 1 year after completion of prexasertib and cyclophosphamide or gemcitabine treatment
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.
Time frame: Up to 3 years from diagnosis
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.
Time frame: prexasertib and cyclophosphamide treatment course 1, days 1 and 2
To characterize the systemic clearance (CL) of cyclophosphamide.
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
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.
Time frame: prexasertib and cyclophosphamide treatment course 1, days 1 and 2
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.
Time frame: prexasertib and cyclophosphamide treatment course 1, days 1 and 2
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.
Time frame: prexasertib and gemcitabine treatment course 1, day 1.
To characterize the systemic clearance (CL) of gemcitabine.
Gemcitabine systemic clearance (CL) is estimated based on course 1, day 1 PK samples.
Time frame: prexasertib and cyclophosphamide treatment course 1, day 1
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.
Time frame: prexasertib and cyclophosphamide treatment course 1, day 1
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — 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.
Supporting information: Study protocol, Sap, Icf
This study is completed, as verified in Feb 2025. You cannot join it, but the record below documents what was studied.
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