We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04238819
Recruitment Status : Recruiting
First Posted : January 23, 2020
Last Update Posted : December 8, 2022
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Brief 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.

Condition or disease Intervention/treatment Phase
Relapsed Solid Tumor Refractory Solid Tumor Drug: Abemaciclib Drug: Irinotecan Drug: Temozolomide Drug: Dinutuximab Drug: GM-CSF Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 117 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : November 9, 2020
Estimated Primary Completion Date : June 30, 2027
Estimated Study Completion Date : December 21, 2028


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 Name: LY2835219

Drug: Irinotecan
Administered IV

Drug: Temozolomide
Administered orally

Experimental: Dose Expansion: Abemaciclib + Irinotecan + Temozolomide
Abemaciclib given orally, irinotecan given IV and temozolomide given orally.
Drug: Abemaciclib
Administered orally
Other Name: LY2835219

Drug: Irinotecan
Administered IV

Drug: Temozolomide
Administered orally

Experimental: Dose Escalation: Abemaciclib + Temozolomide
Abemaciclib and temozolomide given orally.
Drug: Abemaciclib
Administered orally
Other Name: LY2835219

Drug: Temozolomide
Administered orally

Experimental: Dose Expansion: Abemaciclib + Temozolomide
Abemaciclib and temozolomide given orally.
Drug: Abemaciclib
Administered orally
Other Name: LY2835219

Drug: Temozolomide
Administered 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.
Drug: Abemaciclib
Administered orally
Other Name: LY2835219

Drug: Irinotecan
Administered IV

Drug: Temozolomide
Administered orally

Drug: Dinutuximab
Administered IV

Drug: GM-CSF
Administered subQ

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.
Drug: Abemaciclib
Administered orally
Other Name: LY2835219

Drug: Irinotecan
Administered IV

Drug: Temozolomide
Administered orally

Drug: Dinutuximab
Administered IV

Drug: GM-CSF
Administered subQ




Primary Outcome Measures :
  1. Number or Participants with Dose Limiting Toxicities (DLTs) [ Time Frame: Cycle 1 (21 Day Cycle) ]
    Number of Participants with DLTs

  2. Pharmacokinetics (PK): Mean Steady State Concentrations of Abemaciclib [ Time Frame: Cycle 1 through Cycle 3 (21 Day Cycle) ]
    PK: Mean Steady State Concentrations of Abemaciclib

  3. PK: Mean Steady State Concentrations of Irinotecan [ Time Frame: Cycle 1 through Cycle 3 (21 Day Cycle) ]
    PK: Mean Steady State Concentrations of Irinotecan

  4. PK: Mean Steady State Concentrations of Temozolomide [ Time Frame: Cycle 1 through Cycle 3 (21 Day Cycle) ]
    PK: Mean Steady State Concentrations of Temozolomide

  5. Objective Response Rate (ORR): Percentage of Participants with Best Response of Complete Response (CR), Partial Response (PR), or Minimal Response (MR): Part C, only [ Time Frame: Baseline through Disease Progression or Death (Estimated up to 24 Months) ]
    ORR: Percentage of Participants with Best Response of CR, PR or MR per International Neuroblastoma Response Criteria (INRC)


Secondary Outcome Measures :
  1. Overall Response Rate (ORR): Percentage of Participants with Best Response of Complete Response (CR) or Partial Response (PR): Parts A and B, only [ Time Frame: Baseline through Disease Progression or Death (Estimated up to 24 Months) ]
    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)

  2. Duration of Response (DoR) [ Time Frame: 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) ]
    DoR

  3. 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 [ Time Frame: Baseline through Disease Progression or Death Due to Any Cause (Estimated up to 24 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

  4. Disease Control Rate (DCR): Percentage of Participants with a Best Overall Response of CR, PR, MR (Part C, only), and Stable Disease (SD) [ Time Frame: Baseline through Measured Progressive Disease (Estimated up to 24 Months) ]
    DCR: Percentage of Participants with a Best Overall Response of CR, PR, MR (Part C, only), and SD

  5. Progression-Free Survival (PFS): Part C, Only [ Time Frame: Baseline through Progressive Disease or Death (Estimated up to 24 Months) ]
    PFS

  6. Acceptability Questionnaire [ Time Frame: Cycle 2 Day 1 (21 Day Cycles) ]
    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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 ≥0.3 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.
    • 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 or viral load.
  • 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.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04238819


Contacts
Layout table for location contacts
Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Clinicaltrials.gov@lilly.com

Locations
Show Show 29 study locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Layout table for investigator information
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
Additional Information:
Layout table for additonal information
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT04238819    
Other Study ID Numbers: 16950
I3Y-MC-JPCS ( Other Identifier: Eli Lilly and Company )
2019-002931-27 ( EudraCT Number )
First Posted: January 23, 2020    Key Record Dates
Last Update Posted: December 8, 2022
Last Verified: December 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
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.
Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
URL: http://vivli.org/

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eli Lilly and Company:
CDK4
CDK6
Ewing's sarcoma
Neuroblastoma
Malignant rhabdoid tumor
Rhabdomyosarcoma
Osteosarcoma
Brain tumor
Glioblastoma
Malignant glioma
Diffuse intrinsic pontine glioma
Medulloblastoma
Ependymoma
Solid tumor
High-grade glioma
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms
Neuroblastoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Irinotecan
Temozolomide
Dinutuximab
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents