Brain TumorPhase 1NCT04023669

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

A Phase 1 study testing Prexasertib, Cyclophosphamide and Gemcitabine in people with Brain Tumor and Brain Tumor, Recurrent, run by St. Jude Children's Research Hospital at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 1 year to 24 years
Conditions the study is for: Brain Tumor, Brain Tumor, Recurrent, Brain Tumor, Refractory
What is being tested?: Prexasertib, Cyclophosphamide and Gemcitabine
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 21 participants
Where: 1 siteUnited States
Study dates: 8 Aug 2019to 13 Jan 2025
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 1 year to 24 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

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.
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.

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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.

Who cannot join

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).
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.

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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.

Trial locations and contacts

1 site in 1 country.

United States1 site

St. Jude Children's Research Hospital
Memphis, Tennessee, 38105

Other trials in United States

About this study

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

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).

Read the 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.

Conditions: Brain Tumor, Brain Tumor, Recurrent, Brain Tumor, Refractory, Brain Tumor, Pediatric, Medulloblastoma, Medulloblastoma Recurrent
Being tested: Prexasertib, Cyclophosphamide, Gemcitabine, filgrastim, peg-filgrastim
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
Medical subject headings: Brain Neoplasms, Medulloblastoma, Central Nervous System Neoplasms, Microphthalmia, Isolated, with Coloboma 5

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PrexasertibDrug
Also called LY2606368
IV
CyclophosphamideDrug
Also called Cytoxan
IV
GemcitabineDrug
Also called 2'-deoxy-2',2' difluorocytidine monohydrochloride, LY18801, Gemzar®
IV
filgrastimBiological
Also called G-CSF
Given subcutaneously (SQ). Alternatively, pegfilgrastim may be given.
peg-filgrastimBiological
Also called pegylated filgrastim, PEG filgrastim, Neulasta®
Given subcutaneously (SQ). Alternatively, filgrastim may be given.

Study groups in NCT04023669
Study group	Role	What they receive
A: prexasertib + cyclophosphamide	Experimental	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. Receives: Drug: Prexasertib; Drug: Cyclophosphamide; Biological: filgrastim; Biological: peg-filgrastim
B: prexasertib + gemcitabine	Experimental	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. Receives: Drug: Prexasertib; Drug: Gemcitabine; Biological: filgrastim; Biological: peg-filgrastim

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: prexasertib and cyclophosphamide or gemcitabine treatment course 1 days 2 through 7

Secondary outcomes (10)

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: prexasertib and cyclophosphamide treatment course 1, day 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

8 Aug 201913 Jan 2025

First posted17 Jul 2019
Study start8 Aug 2019
Primary completion1 May 2023
Study completion13 Jan 2025

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Brain TumorStudies of the same condition, open and under way.
More trials run by St. Jude Children's Research HospitalThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 21 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04023669
Sponsor's protocol ID: SJELIOT
Other IDs: NCI-2019-04787
Status last verified: Feb 2025
First submitted: 11 Jul 2019
Last updated: 7 Feb 2025
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: 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.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 7 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT04023669
Acronym / sponsor ID: SJELIOT
Conditions: Brain Tumor, Brain Tumor, Recurrent, Brain Tumor, Refractory, Brain Tumor, Pediatric, Medulloblastoma, Medulloblastoma Recurrent
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
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 21 participants (actual)
Lead sponsor: St. Jude Children's Research HospitalUniversity, hospital or other
Collaborators: Eli Lilly and Company
Study start: 8 Aug 2019 (actual)
Primary completion: 1 May 2023 (actual)
Study completion: 13 Jan 2025 (actual)
First posted: 17 Jul 2019 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
A: prexasertib + cyclophosphamide	Experimental	Drug: Prexasertib, Drug: Cyclophosphamide, Biological: filgrastim, Biological: peg-filgrastimStratum 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.
B: prexasertib + gemcitabine	Experimental	Drug: Prexasertib, Drug: Gemcitabine, Biological: filgrastim, Biological: peg-filgrastimStratum 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.

Who may qualify

Ages: 1 year to 24 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (23 listed)

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.
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.

Key exclusion criteria (10 listed)

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).
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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PrexasertibAlso: LY2606368IV	Drug	A: prexasertib + cyclophosphamide, B: prexasertib + gemcitabine
CyclophosphamideAlso: CytoxanIV	Drug	A: prexasertib + cyclophosphamide
GemcitabineAlso: 2'-deoxy-2',2' difluorocytidine monohydrochloride, LY18801, Gemzar®IV	Drug	B: prexasertib + gemcitabine
filgrastimAlso: G-CSFGiven subcutaneously (SQ). Alternatively, pegfilgrastim may be given.	Biological	A: prexasertib + cyclophosphamide, B: prexasertib + gemcitabine
peg-filgrastimAlso: pegylated filgrastim, PEG filgrastim, Neulasta®Given subcutaneously (SQ). Alternatively, filgrastim may be given.	Biological	A: prexasertib + cyclophosphamide, B: prexasertib + gemcitabine

Primary outcome

Estimate the Maximum tolerated dose (MTD)/Recommended Phase 2 Dose (RP2D) of each doublet by stratum
Time frame: 1 month after start of prexasertib and cyclophosphamide or gemcitabine treatment
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.
Time frame: Up to 2 years after start of prexasertib and cyclophosphamide or gemcitabine treatment
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.
Time frame: prexasertib and cyclophosphamide or gemcitabine treatment course 1 days 2 through 7
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.
Time frame: prexasertib and cyclophosphamide or gemcitabine treatment course 1 days 2 through 7
Prexasertib systemic clearance (CL) is estimated based on course 1, days 2 through 7 pharmacokinetic samples.

10 secondary outcomes

Rate of objective response (complete or partial response) by stratum
Time frame: Up to 1 year after completion of prexasertib and cyclophosphamide or gemcitabine treatment
Duration of objective response by stratum
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
Time frame: Up to 3 years from diagnosis
To characterize the area under the concentration-time curve (AUC0-24h) of cyclophosphamide.
Time frame: prexasertib and cyclophosphamide treatment course 1, days 1 and 2
To characterize the systemic clearance (CL) of cyclophosphamide.
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.
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.
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.
Time frame: prexasertib and gemcitabine treatment course 1, day 1.
To characterize the systemic clearance (CL) of gemcitabine.
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).
Time frame: prexasertib and cyclophosphamide treatment course 1, day 1

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2025.
St. Jude Children's Research HospitalLink provided by the sponsor.
Clinical Trials Open at St. JudeLink provided by the sponsor.
St. Jude Brain Tumor StudiesLink provided by the sponsor.
Individual participant dataSharing planned: 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Giles W. Robinson, MD principal investigator

St. Jude Children's Research Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Prexasertib, Cyclophosphamide and Gemcitabine in people with Brain Tumor and Brain Tumor, Recurrent, run by St. Jude Children's Research Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Estimate the Maximum tolerated dose (MTD)/Recommended Phase 2 Dose (RP2D) of each doublet by stratum (time frame: 1 month after start of prexasertib and cyclophosphamide or gemcitabine treatment). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04023669.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2025.