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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Relapsed Solid Tumor; Refractory Solid Tumor
• Intervention / Treatment: Drug: Abemaciclib; Drug: Irinotecan; Drug: Dinutuximab; Drug: GM-CSF; Drug: Temozolomide

• Study Type: Interventional
• Enrollment (Estimated): 117
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or; Phone Number: 1-317-615-4559; Email: ClinicalTrials.gov@lilly.com

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Not yet recruiting
      • The Children's Hospital at Westmead
      • Contact: Phone Number: 0298450459
      • Principal Investigator: Bhavna Padhye
  • Victoria
    • Melbourne, Victoria, Australia, 3052
      • Not yet recruiting
      • Royal Children's Hospital
      • Contact: Phone Number: 61393456592
      • Principal Investigator: Marty Campbell
  • Western Australia
    • Perth, Western Australia, Australia, 6009
      • Recruiting
      • Perth Children's Hospital
      • Principal Investigator: Anne Louise Ryan
• Belgium
  • Oost-Vlaanderen
    • Gent, Oost-Vlaanderen, Belgium, 9000
      • Recruiting
      • UZ Gent
      • Principal Investigator: Bram De Wilde
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Not yet recruiting
      • The Hospital for Sick Children
      • Principal Investigator: Daniel Alexander Morgenstern
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • Not yet recruiting
      • CHU Sainte-Justine
      • Principal Investigator: Pierre Teira
• France
  • Paris, France, 75248
    • Recruiting
    • Institut Curie
    • Principal Investigator: Isabelle AERTS
  • Rhône
    • Lyon, Rhône, France, 69373 CEDEX 08
      • Completed
      • Centre Leon Berard
  • Val-de-Marne
    • Villejuif, Val-de-Marne, France, 94800
      • Completed
      • Gustave Roussy
• Germany
  • Berlin, Germany, 13353
    • Completed
    • Charité Campus Virchow-Klinikum
  • Baden-Württemberg
    • Heidelberg, Baden-Württemberg, Germany, 69120
      • Completed
      • Universitaetsklinikum Heidelberg
  • Nordrhein-Westfalen
    • Essen, Nordrhein-Westfalen, Germany, 45122
      • Completed
      • Universitaetsklinikum Essen
• Italy
  • Lazio
    • Roma, Lazio, Italy, 168
      • Completed
      • Fondazione Policlinico Universitario Agostino Gemelli
• Spain
  • València, Spain, 46026
    • Active, not recruiting
    • Hospital Universitari i Politecnic La Fe
  • Barcelona [Barcelona]
    • Barcelona, Barcelona [Barcelona], Spain, 8035
      • Active, not recruiting
      • Hospital Universitari Vall d'Hebron
  • Madrid, Comunidad De
    • Madrid, Madrid, Comunidad De, Spain, 28009
      • Active, not recruiting
      • Hospital Infantil Universitario Nino Jesus
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Recruiting
      • Phoenix Children's Hospital
      • Principal Investigator: Lindsey Hoffman
  • California
    • Los Angeles, California, United States, 90095-1752
      • Recruiting
      • The Regents of the University of California - Los Angeles (UCLA Pediatrics)
      • Principal Investigator: Noah Federman
    • Oakland, California, United States, 94611
      • Recruiting
      • Kaiser Permanente Oakland
      • Principal Investigator: Aarati Rao
    • Roseville, California, United States, 95661
      • Recruiting
      • Kaiser Permanente Roseville
      • Principal Investigator: Aarati Rao
    • Santa Clara, California, United States, 95051
      • Recruiting
      • Kaiser Permanente Santa Clara
      • Principal Investigator: Aarati Rao
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Not yet recruiting
      • Children's Hospital Colorado
      • Principal Investigator: Margaret Macy
      • Contact: Phone Number: 720-777-8856
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Not yet recruiting
      • Connecticut Children's Medical Center
      • Principal Investigator: Andrea Orsey
  • Florida
    • Miami, Florida, United States, 33155
      • Not yet recruiting
      • Nicklaus Children's Hospital
      • Principal Investigator: Guillermo De Angulo
      • Contact: Phone Number: 786-624-3513
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago Medical Center
      • Principal Investigator: Ami V. Desai
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Riley Hospital for Children at Indiana University Health
      • Principal Investigator: Melissa Bear
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Not yet recruiting
      • University of Louisville, Norton Children's Research Institute
      • Principal Investigator: Kerry Kaye McGowan
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Recruiting
      • Spectrum Health
      • Principal Investigator: David Hoogstra
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Not yet recruiting
      • Children's Hospital & Medical Center
      • Principal Investigator: Jenna Allison
  • New York
    • New Hyde Park, New York, United States, 11040
      • Recruiting
      • Cohen Children's Medical Center
      • Principal Investigator: Julie Krystal
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Recruiting
      • Atrium Health - Carolinas Medical Center
      • Principal Investigator: Thomas Bennett Russell
  • Ohio
    • Akron, Ohio, United States, 44308
      • Not yet recruiting
      • Akron Children's Hospital
      • Principal Investigator: Erin Wright
    • Cincinnati, Ohio, United States, 45229
      • Recruiting
      • Cincinnati Children's Hospital Medical Center
      • Principal Investigator: Joseph Pressey
    • Columbus, Ohio, United States, 43205
      • Recruiting
      • Nationwide Children's Hospital
      • Principal Investigator: Nilay Shah
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia (CHOP)
      • Principal Investigator: frank balis
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Recruiting
      • Lifespan Cancer Institute
      • Principal Investigator: Bradley DeNardo
  • Texas
    • Dallas, Texas, United States, 75235
      • Recruiting
      • Children's Health
      • Principal Investigator: Tanya Watt
    • Houston, Texas, United States, 77030
      • Not yet recruiting
      • Texas Children's Hospital
      • Contact: Phone Number: 832-824-4646
      • Principal Investigator: Jennie Foster
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Not yet recruiting
      • Intermountain - Primary Children's Hospital
      • Principal Investigator: Matthew Steven Dietz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation: Abemaciclib + Irinotecan + Temozolomide; Abemaciclib given orally, irinotecan given intravenously (IV) and temozolomide given orally.	Drug: Abemaciclib; Administered orally; Other Names: LY2835219; Drug: Irinotecan; Administered IV; Drug: Temozolomide; Administered orally or IV
Experimental: Dose Expansion: Abemaciclib + Irinotecan + Temozolomide; Abemaciclib given orally, irinotecan given IV and temozolomide given orally.	Drug: Abemaciclib; Administered orally; Other Names: LY2835219; Drug: Irinotecan; Administered IV; Drug: Temozolomide; Administered orally or IV
Experimental: Dose Escalation: Abemaciclib + Temozolomide; Abemaciclib and temozolomide given orally.	Drug: Abemaciclib; Administered orally; Other Names: LY2835219; Drug: Temozolomide; Administered orally or IV
Experimental: Dose Expansion: Abemaciclib + Temozolomide; Abemaciclib and temozolomide given orally.	Drug: Abemaciclib; Administered orally; Other Names: LY2835219; Drug: Temozolomide; Administered orally or IV
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.	Drug: Abemaciclib; Administered orally; Other Names: LY2835219; Drug: Irinotecan; Administered IV; Drug: Dinutuximab; Administered IV; Drug: GM-CSF; Administered subQ; Drug: Temozolomide; Administered 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.	Drug: Abemaciclib; Administered orally; Other Names: LY2835219; Drug: Irinotecan; Administered IV; Drug: Dinutuximab; Administered IV; Drug: GM-CSF; Administered subQ; Drug: Temozolomide; Administered orally or IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number or Participants with Dose Limiting Toxicities (DLTs)	Number of Participants with DLTs	Cycle 1 (21 Day Cycle)
Pharmacokinetics (PK): Mean Steady State Concentrations of Abemaciclib	PK: Mean Steady State Concentrations of Abemaciclib	Cycle 1 through Cycle 3 (21 Day Cycle)
PK: Mean Steady State Concentrations of Irinotecan	PK: Mean Steady State Concentrations of Irinotecan	Cycle 1 through Cycle 3 (21 Day Cycle)
PK: Mean Steady State Concentrations of Temozolomide	PK: Mean Steady State Concentrations of Temozolomide	Cycle 1 through Cycle 3 (21 Day Cycle)
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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)
Progression-Free Survival (PFS): Part C, Only	PFS	Baseline through Progressive Disease or Death (Estimated up to 24 Months)
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)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: 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), Eli Lilly and Company

Publications and helpful links

Helpful 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

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2020
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): October 28, 2028

Study Registration Dates

• First Submitted: January 22, 2020
• First Submitted That Met QC Criteria: January 22, 2020
• First Posted (Actual): January 23, 2020

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Brain tumor; Medulloblastoma; Ependymoma; Solid tumor; Glioblastoma; Rhabdomyosarcoma; Osteosarcoma; Neuroblastoma; Ewing's sarcoma; CDK4; CDK6; Malignant rhabdoid tumor; Malignant glioma; Diffuse intrinsic pontine glioma; High-grade glioma; Recurrent neuroblastoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral; Neoplasms; Neuroblastoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Temozolomide; Irinotecan; Dinutuximab
• Other Study ID Numbers: 16950 (H. Lee Moffitt Cancer Center); I3Y-MC-JPCS (Other Identifier: Eli Lilly and Company); 2019-002931-27 (EudraCT Number); 2023-506778-11-00 (Other Identifier: EU Trial Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Time Frame: 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.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No