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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04238819




Registration number
NCT04238819
Ethics application status
Date submitted
22/01/2020
Date registered
23/01/2020

Titles & IDs
Public title
A Study of Abemaciclib (LY2835219) in Combination With Other Anti-Cancer Treatments in Children and Young Adult Participants With Solid Tumors, Including Neuroblastoma
Scientific title
A Phase 1b/2 Study of Abemaciclib in Combination With Irinotecan and Temozolomide (Part A) and Abemaciclib in Combination With Temozolomide (Part B) in Pediatric and Young Adult Patients With Relapsed/Refractory Solid Tumors and Abemaciclib in Combination With Dinutuximab, GM-CSF, Irinotecan, and Temozolomide in Pediatric and Young Adult Patients With Relapsed/Refractory Neuroblastoma (Part C)
Secondary ID [1] 0 0
I3Y-MC-JPCS
Secondary ID [2] 0 0
16950
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed Solid Tumor 0 0
Refractory Solid Tumor 0 0
Condition category
Condition code
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Children's - Other

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Abemaciclib
Treatment: Drugs - Irinotecan
Treatment: Drugs - Temozolomide
Treatment: Drugs - Dinutuximab
Treatment: Drugs - GM-CSF

Experimental: Dose Escalation: Abemaciclib + Irinotecan + Temozolomide - Abemaciclib given orally, irinotecan given intravenously (IV) and temozolomide given orally.

Experimental: Dose Expansion: Abemaciclib + Irinotecan + Temozolomide - Abemaciclib given orally, irinotecan given IV and temozolomide given orally.

Experimental: Dose Escalation: Abemaciclib + Temozolomide - Abemaciclib and temozolomide given orally.

Experimental: Dose Expansion: Abemaciclib + Temozolomide - Abemaciclib and temozolomide given orally.

Experimental: Part C Stage 1: Abemaciclib in Combination with Dinutuximab, GM-CSF, Irinotecan, and Temozolomide - Abemaciclib given orally, dinutuximab given IV, granulocyte macrophage colony-stimulating factor (GM-CSF) given subcutaneously (subQ), irinotecan given IV and temozolomide given orally or IV.

Experimental: Part C Stage 2: Abemaciclib in Combination with Dinutuximab, GM-CSF, Irinotecan, and Temozolomide - Abemaciclib given orally, dinutuximab given IV, GM-CSF given subQ, irinotecan given IV and temozolomide given orally or IV.


Treatment: Drugs: Abemaciclib
Administered orally

Treatment: Drugs: Irinotecan
Administered IV

Treatment: Drugs: Temozolomide
Administered orally or IV

Treatment: Drugs: Dinutuximab
Administered IV

Treatment: Drugs: GM-CSF
Administered subQ
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number or Participants with Dose Limiting Toxicities (DLTs)
Timepoint [1] 0 0
Cycle 1 (21 Day Cycle)
Primary outcome [2] 0 0
Pharmacokinetics (PK): Mean Steady State Concentrations of Abemaciclib
Timepoint [2] 0 0
Cycle 1 through Cycle 3 (21 Day Cycle)
Primary outcome [3] 0 0
PK: Mean Steady State Concentrations of Irinotecan
Timepoint [3] 0 0
Cycle 1 through Cycle 3 (21 Day Cycle)
Primary outcome [4] 0 0
PK: Mean Steady State Concentrations of Temozolomide
Timepoint [4] 0 0
Cycle 1 through Cycle 3 (21 Day Cycle)
Primary outcome [5] 0 0
Objective Response Rate (ORR): Percentage of Participants with Best Response of Complete Response (CR), Partial Response (PR), or Minimal Response (MR): Part C, only
Timepoint [5] 0 0
Baseline through Disease Progression or Death (Estimated up to 24 Months)
Secondary outcome [1] 0 0
Overall Response Rate (ORR): Percentage of Participants with Best Response of Complete Response (CR) or Partial Response (PR): Parts A and B, only
Timepoint [1] 0 0
Baseline through Disease Progression or Death (Estimated up to 24 Months)
Secondary outcome [2] 0 0
Duration of Response (DoR)
Timepoint [2] 0 0
Date of First Evidence of a CR, PR, or MR (Part C, only) to Date of Objective Disease Progression or Death Due to Any Cause (Estimated up to 24 Months)
Secondary outcome [3] 0 0
Clinical Benefit Rate (CBR): Percentage of Participants with Best Overall Response of CR, PR, MR (Part C, only) or SD With a Duration of At Least 6 Months
Timepoint [3] 0 0
Baseline through Disease Progression or Death Due to Any Cause (Estimated up to 24 Months)
Secondary outcome [4] 0 0
Disease Control Rate (DCR): Percentage of Participants with a Best Overall Response of CR, PR, MR (Part C, only), and Stable Disease (SD)
Timepoint [4] 0 0
Baseline through Measured Progressive Disease (Estimated up to 24 Months)
Secondary outcome [5] 0 0
Progression-Free Survival (PFS): Part C, Only
Timepoint [5] 0 0
Baseline through Progressive Disease or Death (Estimated up to 24 Months)
Secondary outcome [6] 0 0
Acceptability Questionnaire
Timepoint [6] 0 0
Cycle 2 Day 1 (21 Day Cycles)

Eligibility
Key inclusion criteria
* Parts A and B only:

* Participants must be less than or equal to (=)18 years of age.
* Body weight greater than or equal to (=)10 kilograms and body surface area (BSA) =0.5
* Participants with any relapsed/refractory malignant solid tumor (excluding lymphoma), including central nervous system tumors, that have progressed on standard therapies.
* For sites that are actively enrolling Parts B and C, participants with neuroblastoma who are eligible for Part C will be excluded from Part B unless approved by Lilly CRP/CRS.
* Part C only:

* Participants must be less than (<) 21 years of age.
* Participants have a BSA =0.2 m².
* Participants with first relapse/refractory neuroblastoma.
* All Parts

* Participants must have measurable or evaluable disease by RECIST v1.1 or RANO.
* A Lansky score =50 for participants <16 years of age or Karnofsky score =50 for participants =16 years of age.
* Participants must have discontinued all previous treatments for cancer or investigational agents and must have recovered from the acute effects to Grade =1 at the time of enrollment.
* Able to swallow and/or have a gastric/nasogastric tube.
* Adequate hematologic and organ function =2 weeks (14 days) prior to first dose of study drug.
* Females of reproductive potential must have negative urine or serum pregnancy test at baseline (within 7 days prior to starting treatment).
* Female participants of reproductive potential must agree to use highly effective contraceptive precautions during the trial. For abemaciclib, females should use contraception for at least 3 weeks following the last abemaciclib. For other study drugs, highly effective contraceptive precautions (and avoiding sperm donation) must be used according to their label.
* Life expectancy of at least 8 weeks and able to complete at least 1 cycle of treatment.
* Caregivers and participants willing to make themselves available for the duration of the trial.
Minimum age
No limit
Maximum age
21 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Received allogenic bone marrow or solid organ transplant.
* Received live vaccination.
* Intolerability or hypersensitivity to any of the study treatments or its components.
* Diagnosed and/or treated additional malignancy within 3 years prior to enrollment that may affect the interpretation of results, with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or curatively resected in situ cervical and/or breast cancers.
* Pregnant or breastfeeding.
* Active systemic infections.
* Serious and/or uncontrolled preexisting medical condition(s) that would preclude participation in this study.
* Parts A and C only: Have a bowel obstruction.
* Prior treatment with drugs known to be strong inhibitors or inducers of isoenzyme cytochrome P450 3A (CYP3A) or strong inhibitors of uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) if the treatment cannot be discontinued or switched to a different medication at least 5 half-lives prior to starting study drug.
* Received prior treatment with cyclin-dependent kinase (CDK) 4 & 6 inhibitor.
* Part C only: Received prior systemic therapy for relapsed/refractory neuroblastoma.
* Part C only, have received prior anti-GD2 therapy during induction phase.
* Currently enrolled in any other clinical study involving an investigational product or non-approved use of a drug or device.
* Has received an experimental treatment in a clinical trial within the last 30 days or 5 half-lives, whichever is longer.

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
Single group
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
9/11/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/04/2025
Actual
Sample size
Target
117
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Indiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Rhode Island
Country [10] 0 0
Belgium
State/province [10] 0 0
Oost-Vlaanderen
Country [11] 0 0
France
State/province [11] 0 0
Rhône
Country [12] 0 0
France
State/province [12] 0 0
Val-de-Marne
Country [13] 0 0
France
State/province [13] 0 0
Paris
Country [14] 0 0
Germany
State/province [14] 0 0
Baden-Württemberg
Country [15] 0 0
Germany
State/province [15] 0 0
Nordrhein-Westfalen
Country [16] 0 0
Germany
State/province [16] 0 0
Berlin
Country [17] 0 0
Italy
State/province [17] 0 0
Lazio
Country [18] 0 0
Japan
State/province [18] 0 0
Tokyo
Country [19] 0 0
Spain
State/province [19] 0 0
Barcelona [Barcelona]
Country [20] 0 0
Spain
State/province [20] 0 0
Madrid, Comunidad De
Country [21] 0 0
Spain
State/province [21] 0 0
València

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eli Lilly and Company
Address
Country

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Address 0 0
Eli Lilly and Company
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?
Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR)
When will data be available (start and end dates)?
Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
Available to whom?
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://vivli.org/


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04238819