A Study of Abemaciclib (LY2835219) in Combination With Other Anti-Cancer Treatments in Children and Young Adult Participants With Solid Tumors, Including Neuroblastoma

Refractory Solid Tumor Clinical Trial

Official 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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04238819
• Other study ID #: 16950
• Secondary ID: I3Y-MC-JPCS2019-
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: November 9, 2020
• Est. completion date: October 2028

Study information

• Verified date: May 2024
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study's purpose is to see if the drug, abemaciclib, is safe and effective when given with other drugs to kill cancer cells. The study is open to children and young adults with solid tumors, including neuroblastoma, that did not respond or grew during other anti-cancer treatment. For each participant, the study is estimated to last up to 2 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 117
• Est. completion date: October 2028
• Est. primary completion date: May 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 21 Years

Eligibility

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.

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.

Related Conditions & MeSH terms

• Neoplasms
• Neuroblastoma
• Refractory Solid Tumor
• Relapsed Solid Tumor

Intervention

Drug:
• Abemaciclib
Administered orally
• Irinotecan
Administered IV
• Temozolomide
Administered orally or IV
• Dinutuximab
Administered IV
• GM-CSF
Administered subQ

Locations

Country	Name	City	State
Australia	Royal Children's Hospital	Melbourne	Victoria
Australia	Perth Children's Hospital	Perth	Western Australia
Australia	The Children's Hospital at Westmead	Westmead	New South Wales
Belgium	UZ Gent	Gent	Oost-Vlaanderen
Canada	CHU Sainte-Justine	Montreal	Quebec
Canada	The Hospital for Sick Children	Toronto	Ontario
France	Centre Leon Berard	Lyon	Rhône
France	Institut Curie	Paris
France	Gustave Roussy	Villejuif	Val-de-Marne
Germany	Charité Campus Virchow-Klinikum	Berlin
Germany	Universitaetsklinikum Essen	Essen	Nordrhein-Westfalen
Germany	Universitaetsklinikum Heidelberg	Heidelberg	Baden-Württemberg
Italy	Fondazione Policlinico Universitario Agostino Gemelli	Roma	Lazio
Spain	Hospital Universitari Vall d'Hebron	Barcelona	Barcelona [Barcelona]
Spain	Hospital Infantil Universitario Niño Jesús	Madrid	Madrid, Comunidad De
Spain	Hospital Universitari i Politecnic La Fe	València
United States	Akron Children's Hospital	Akron	Ohio
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Atrium Health - Carolinas Medical Center	Charlotte	North Carolina
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Children's Health	Dallas	Texas
United States	Spectrum Health	Grand Rapids	Michigan
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	Texas Children's Hospital	Houston	Texas
United States	Riley Hospital for Children at Indiana University Health	Indianapolis	Indiana
United States	The Regents of the University of California - Los Angeles (UCLA Pediatrics)	Los Angeles	California
United States	University of Louisville, Norton Children's Research Institute	Louisville	Kentucky
United States	Nicklaus Children's Hospital	Miami	Florida
United States	Cohen Children's Medical Center	New Hyde Park	New York
United States	Kaiser Permanente Oakland	Oakland	California
United States	Children's Hospital & Medical Center	Omaha	Nebraska
United States	Children's Hospital of Philadelphia (CHOP)	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Lifespan Cancer Institute	Providence	Rhode Island
United States	Kaiser Permanente Roseville	Roseville	California
United States	Intermountain - Primary Children's Hospital	Salt Lake City	Utah
United States	Kaiser Permanente Santa Clara	Santa Clara	California

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Germany,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number or Participants with Dose Limiting Toxicities (DLTs)	Number of Participants with DLTs	Cycle 1 (21 Day Cycle)
Primary	Pharmacokinetics (PK): Mean Steady State Concentrations of Abemaciclib	PK: Mean Steady State Concentrations of Abemaciclib	Cycle 1 through Cycle 3 (21 Day Cycle)
Primary	PK: Mean Steady State Concentrations of Irinotecan	PK: Mean Steady State Concentrations of Irinotecan	Cycle 1 through Cycle 3 (21 Day Cycle)
Primary	PK: Mean Steady State Concentrations of Temozolomide	PK: Mean Steady State Concentrations of Temozolomide	Cycle 1 through Cycle 3 (21 Day Cycle)
Primary	Objective Response Rate (ORR): Percentage of Participants with Best Response of Complete Response (CR), Partial Response (PR), or Minimal Response (MR): Part C, only	ORR: Percentage of Participants with Best Response of CR, PR or MR per International Neuroblastoma Response Criteria (INRC)	Baseline through Disease Progression or Death (Estimated up to 24 Months)
Secondary	Overall Response Rate (ORR): Percentage of Participants with Best Response of Complete Response (CR) or Partial Response (PR): Parts A and B, only	ORR: Percentage of Participants with Best Response of CR or PR per Response Evaluation Criteria in Solid Tumors (RECIST) or Response Assessment in Neuro-Oncology (RANO)	Baseline through Disease Progression or Death (Estimated up to 24 Months)
Secondary	Duration of Response (DoR)	DoR	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	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	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	Baseline through Disease Progression or Death Due to Any Cause (Estimated up to 24 Months)
Secondary	Disease Control Rate (DCR): Percentage of Participants with a Best Overall Response of CR, PR, MR (Part C, only), and Stable Disease (SD)	DCR: Percentage of Participants with a Best Overall Response of CR, PR, MR (Part C, only), and SD	Baseline through Measured Progressive Disease (Estimated up to 24 Months)
Secondary	Progression-Free Survival (PFS): Part C, Only	PFS	Baseline through Progressive Disease or Death (Estimated up to 24 Months)
Secondary	Acceptability Questionnaire	Participants were evaluated for abemaciclib acceptability (palatability and ease of administration) using a 5-category questionnaire. Participants were asked to answer one of the following to describe the acceptability of abemaciclib: Very difficult, difficult, neither easy nor difficult, easy, or very easy	Cycle 2 Day 1 (21 Day Cycles)

External Links

•   A Study of Abemaciclib (LY2835219) in Combination With Temozolomide and Irinotecan and Abemaciclib in Combination With Temozolomide in Children and Young Adult Participants With Solid Tumors