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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04023669


Additional trial details provided through ANZCTR are available at the end of this record.


Registration number
NCT04023669
Ethics application status
Date submitted
11/07/2019
Date registered
17/07/2019

Titles & IDs
Public 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
Scientific 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
Secondary ID [1] 0 0
NCI-2019-04787
Secondary ID [2] 0 0
SJELIOT
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Brain Tumor 0 0
Brain Tumor, Recurrent 0 0
Brain Tumor, Refractory 0 0
Brain Tumor, Pediatric 0 0
Medulloblastoma 0 0
Medulloblastoma Recurrent 0 0
Medulloblastoma, Non-WNT/Non-SHH 0 0
Medulloblastoma, Non-WNT/Non-SHH, Group 3 0 0
Medulloblastoma, Non-WNT/Non-SHH, Group 4 0 0
Brain Cancer 0 0
CNS Cancer 0 0
CNS Tumor 0 0
CNS Neoplasm 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain
Cancer 0 0 0 0
Children's - Brain
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Prexasertib
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Gemcitabine
Treatment: Other - filgrastim
Treatment: Other - peg-filgrastim

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.

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.


Treatment: Drugs: Prexasertib
IV

Treatment: Drugs: Cyclophosphamide
IV

Treatment: Drugs: Gemcitabine
IV

Treatment: Other: filgrastim
Given subcutaneously (SQ). Alternatively, pegfilgrastim may be given.

Treatment: Other: peg-filgrastim
Given subcutaneously (SQ). Alternatively, filgrastim may be given.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Estimate the Maximum tolerated dose (MTD)/Recommended Phase 2 Dose (RP2D) of each doublet by stratum
Timepoint [1] 0 0
1 month after start of prexasertib and cyclophosphamide or gemcitabine treatment
Primary outcome [2] 0 0
To determine the safety and tolerability of combination treatment with prexasertib and cyclophosphamide or gemcitabine.
Timepoint [2] 0 0
Up to 2 years after start of prexasertib and cyclophosphamide or gemcitabine treatment
Primary outcome [3] 0 0
To characterize the area under the concentration-time curve (AUC0-8) of prexasertib in combination with cyclophosphamide or gemcitabine.
Timepoint [3] 0 0
prexasertib and cyclophosphamide or gemcitabine treatment course 1 days 2 through 7
Primary outcome [4] 0 0
To characterize the systemic clearance (CL) of prexasertib in combination with cyclophosphamide or gemcitabine.
Timepoint [4] 0 0
prexasertib and cyclophosphamide or gemcitabine treatment course 1 days 2 through 7
Secondary outcome [1] 0 0
Rate of objective response (complete or partial response) by stratum
Timepoint [1] 0 0
Up to 1 year after completion of prexasertib and cyclophosphamide or gemcitabine treatment
Secondary outcome [2] 0 0
Duration of objective response by stratum
Timepoint [2] 0 0
Up to 1 year after completion of prexasertib and cyclophosphamide or gemcitabine treatment
Secondary outcome [3] 0 0
Progression-free survival for patients treated with prexasertib and cyclophosphamide or gemcitabine
Timepoint [3] 0 0
Up to 3 years from diagnosis
Secondary outcome [4] 0 0
To characterize the area under the concentration-time curve (AUC0-24h) of cyclophosphamide.
Timepoint [4] 0 0
prexasertib and cyclophosphamide treatment course 1, days 1 and 2
Secondary outcome [5] 0 0
To characterize the systemic clearance (CL) of cyclophosphamide.
Timepoint [5] 0 0
prexasertib and cyclophosphamide treatment course 1, days 1 and 2
Secondary outcome [6] 0 0
To characterize the area under the concentration-time curve (AUC0-24h) of 4-hydroxy-cyclophosphamide.
Timepoint [6] 0 0
prexasertib and cyclophosphamide treatment course 1, days 1 and 2
Secondary outcome [7] 0 0
To characterize the area under the concentration-time curve (AUC0-24h) of carboxyethylphosphoramide mustard.
Timepoint [7] 0 0
prexasertib and cyclophosphamide treatment course 1, days 1 and 2
Secondary outcome [8] 0 0
To characterize the area under the concentration-time curve (AUC0-4h) of gemcitabine.
Timepoint [8] 0 0
prexasertib and gemcitabine treatment course 1, day 1.
Secondary outcome [9] 0 0
To characterize the systemic clearance (CL) of gemcitabine.
Timepoint [9] 0 0
prexasertib and cyclophosphamide treatment course 1, day 1
Secondary outcome [10] 0 0
To characterize the area under the concentration-time curve (AUC0-4h) of gemcitabine triphosphate (only at St. Jude Children's Research Hospital).
Timepoint [10] 0 0
prexasertib and cyclophosphamide treatment course 1, day 1

Eligibility
Key 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.
Minimum age
1 Year
Maximum age
24 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/08/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/03/2025
Actual
Sample size
Target
Accrual to date
Final
21
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Tennessee

Funding & Sponsors
Primary sponsor type
Other
Name
St. Jude Children's Research Hospital
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Eli Lilly and Company
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Giles W. Robinson, MD
Address 0 0
St. Jude Children's Research Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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 document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF)
When will data be available (start and end dates)?
Data will be made available at the time of article publication.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

TypeOther DetailsAttachment
Informed consent form https://cdn.clinicaltrials.gov/large-docs/69/NCT04023669/ICF_000.pdf



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04023669

Additional trial details provided through ANZCTR
Accrual to date
1
Recruiting in Australia
Recruitment state(s)
WA
Funding & Sponsors
Primary sponsor
Primary sponsor name
Primary sponsor address
Primary sponsor country
Secondary sponsor category [1] 28
Other Collaborative groups
Name [1] 28
ANZCHOG
Address [1] 28
27-31 Wright Street, Clayton VIC 3168
Country [1] 28
Australia
Ethics approval
Ethics application status
 
Public notes
Perth Children's Hospital

Contacts
Principal investigator
Title 141 0
Dr
Name 141 0
Nick Gottardo
Address 141 0
15 Hospital Ave, Nedlands WA 6009
Country 141 0
Australia
Phone 141 0
+618 6456 0241
Fax 141 0
+618 6456 0241
Email 141 0
Nick.Gottardo@health.wa.gov.au
Contact person for public queries
Title 142 0
Mrs
Name 142 0
Robyn Strong
Address 142 0
27-31 Wright Street, Clayton VIC 3168
Country 142 0
Australia
Phone 142 0
+613 8572 2684
Fax 142 0
+613 9902 4810
Email 142 0
Robyn.strong@hudson.org.au
Contact person for scientific queries
Title 143 0
Dr
Name 143 0
Nick Gottardo
Address 143 0
15 Hospital Ave, Nedlands WA 6009
Country 143 0
Australia
Phone 143 0
+618 6456 0241
Fax 143 0
+618 6456 0241
Email 143 0
Nick.Gottardo@health.wa.gov.au