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Completed

NCT Number: NCT04238819

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

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.

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Key information

Conditions

Relapsed Solid Tumor Astrocytoma Brain Diseases Brain Neoplasms Brain Stem Neoplasms Central Nervous System Diseases Central Nervous System Neoplasms Diffuse Intrinsic Pontine Glioma Ependymoma Glioblastoma Glioma Infratentorial Neoplasms Medulloblastoma Myosarcoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Bone Tissue Neoplasms, Complex and Mixed Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Muscle Tissue Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Nervous System Diseases Nervous System Neoplasms Neuroblastoma Neuroectodermal Tumors Neuroectodermal Tumors, Primitive Neuroectodermal Tumors, Primitive, Peripheral Osteosarcoma Refractory Solid Tumor Rhabdoid Tumor Rhabdomyosarcoma Sarcoma Sarcoma, Ewing

Age range

Up to 21 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Perth Children's Hospital, Perth, Western Australia, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Abemaciclib

Drug

Administered orally

Other names: LY2835219

Irinotecan

Drug

Administered IV

Temozolomide

Drug

Administered orally

Dinutuximab

Drug

Administered IV

GM-CSF

Drug

Administered SC

Primary outcomes

  1. Recommended Phase 2 Dose (RP2D) of Abemaciclib in Combination With Irinotecan and Temozolomide (Part A)

    Time frame: Cycles 1 and 2 (21 Day Cycles)

    The RP2D of abemaciclib was determined based on the totality of safety, tolerability, and pharmacokinetic results. RP2D of abemaciclib in combination with 50 mg/m²/day irinotecan and 100 mg/m²/day temozolomide on days 1-5 of 21-day cycles was reported.

  2. Number or Participants With Dose Limiting Toxicities (DLTs) in Part A

    Time frame: Cycle 1 (21 Day Cycle)

    DLT was 1 of the following adverse events likely related to abemaciclib/combination and fulfils any 1 of the following criteria graded per National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0:

    • Any non-hematologic Grade (G) ≥3 toxicity, except:
    • G3 diarrhea lasting <72 hour (h)
    • Acute irinotecan-associated diarrhea lasting <7 days
    • G≥3 nausea, vomiting, constipation that lasts <72 h
    • G3 mucositis/stomatitis lasting <72 h
    • G3 fever/infection
    • G≥3 electrolyte abnormality that lasts <72 h, is not complicated, and resolves spontaneously or responds to conventional medication;
    • G≥3 amylase/lipase that is not associated with symptoms/clinical manifestations of pancreatitis; or
    • AST/ALT elevation resolving to eligibility criteria within 7 days;
    • Hematologic toxicities considered a DLT:
    • A >14-day Cycle 2 delay due to neutropenia/thrombocytopenia
    • G≥3 thrombocytopenia with significant bleeding; or
    • G≥ 4 neutropenic fever

  3. Maximum Tolerated Dose (MTD) of Abemaciclib in Part A

    Time frame: Cycle 1 (21 Days)

    The MTD was defined as the highest dose level at which less than 33% of participants experienced a DLT.

  4. Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Tlast (AUC0-tlast) of Abemaciclib in Part A

    Time frame: Pre-dose, 1, 2.5, 4, and 6 hours post Day 1 dose of Cycle 1 and Cycle 2 (21 Day Cycle)

    PK: (AUC0-tlast) was reported.

  5. PK: (AUC0-tlast) of Irinotecan in Part A

    Time frame: 2.5, 4, and 6 hours post Day 1 dose of Cycle 1 and Cycle 2 (21 Day Cycle)

    PK: AUC0-tlast) was reported.

  6. PK: (AUC0-tlast) of Temozolomide in Part A

    Time frame: 1, 2.5, 4, and 6 hours post Day 1 dose of Cycle 1 and Cycle 2 (21 Day Cycle)

    PK: AUC0-tlast was reported.

  7. RP2D of Abemaciclib in Combination With Temozolomide (Part B)

    Time frame: Cycles 1 and 2 (21 Day Cycles)

    The RP2D of abemaciclib was determined based on the totality of safety, tolerability, and pharmacokinetic results. RP2D of abemaciclib in combination with 150 mg/m²/day temozolomide on days 1-5 of 21-day cycles was reported.

  8. Number or Participants With DLTs in Part B

    Time frame: Cycle 1 (21 Day Cycle)

    A DLT was 1 of the following adverse events likely related to abemaciclib/combination and fulfils any 1 of the following criteria graded as per National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0:

    • Any non-hematologic Grade (G) ≥3 toxicity, except:
    • G3 diarrhea lasting <72 hr
    • Acute irinotecan-associated diarrhea lasting <7 days
    • G≥3 nausea, vomiting, constipation that lasts <72 hr
    • G3 mucositis/stomatitis lasting <72 hr
    • G3 fever/infection
    • G≥3 electrolyte abnormality that lasts <72 hr, is not complicated, and resolves spontaneously or responds to conventional medication;
    • G≥3 amylase/lipase that is not associated with symptoms/clinical manifestations of pancreatitis; or
    • AST/ALT elevation resolving to eligibility criteria within 7 days;
    • Hematologic toxicities considered a DLT:
    • A >14-day Cycle 2 delay due to neutropenia/thrombocytopenia
    • G≥3 thrombocytopenia with significant bleeding; or
    • G≥ 4 neutropenic fever

  9. MTD of Abemaciclib in Part B

    Time frame: Cycle 1 (21 Days)

    The MTD was defined as the highest dose level at which less than 33% of participants experienced a DLT.

  10. PK: AUC0-tlast of Abemaciclib in Part B

    Time frame: Pre-dose, 1, 2.5, 4, and 6 hours post Day 1 dose of Cycle 1 and Cycle 2 (21 Day Cycle)

    PK: AUC0-tlast was reported.

  11. PK: AUC0-tlast of Temozolomide in Part B

    Time frame: 1, 2.5, 4, and 6 hours post Day 1 dose of Cycle 1 and Cycle 2 (21 Day Cycle)

    PK: AUC0-tlast was reported.

  12. Number of Participants With Overall Response Rate (ORR) in Part C.

    Time frame: Date of first dose to disease progression or death (Up to 25 Months)

    ORR: Number of participants with best response of Complete Response (CR), Partial Response (PR), or Minor Response (MR) per International Neuroblastoma Response Criteria (INRC).

    • CR is defined as complete response in all response components:
    • Primary Tumor: <10 mm residual soft tissue primary site and complete resolution of MIBG-avid tumors
    • Soft tissue and bone metastatic response: nonprimary target and nontarget lesions <10 mm and nodes identified as targets decreased to short axis <10mm and MIBG-avid update of nonprimary lesions completely resolved
    • Bone marrow response: no tumor infiltration on reassessment; disappearance of all target lesions;
    • PR is defined as PR in >1component and all other components are either CR, minimal disease (MD) (bone marrow only), PR (soft tissue or bone), or not involved (NI) and no components with progressive disease (PD).
    • MR is defined PR or CR in >1 component and SD in >1 component and no component with PD

Secondary outcomes

  1. Percentage of Participants With Overall Response Rate (ORR): Part A

    Time frame: Date of first dose to disease progression or death (Up to 25 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).

    RECIST was used for solid tumors and RANO was used for brain tumors.

    • CR is defined as the disappearance of all target lesions (RECIST) and disappearance of all enhancing measurable and non-measurable disease, no new lesions; stable or improved non-enhancing lesions; and patient must be off corticosteroids and stable or improved clinically (RANO).
    • PR is defined as a 30% decrease in the sum of diameters of target lesions (RECIST) and >50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, no new lesions, stable/improved non-enhancing lesions on same or lower dose of corticosteroids and patient is stable or improved clinically (RANO).

  2. Percentage of Participants With ORR: Part B

    Time frame: Date of first dose to disease progression or death (Up to 25 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).

    RECIST was used for solid tumors and RANO was used for brain tumors.

    • CR is defined as the disappearance of all target lesions (RECIST) and disappearance of all enhancing measurable and non-measurable disease, no new lesions; stable or improved non-enhancing lesions; and patient must be off corticosteroids and stable or improved clinically (RANO).
    • PR is defined as a 30% decrease in the sum of diameters of target lesions (RECIST) and >50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, no new lesions, stable/improved non-enhancing lesions on same or lower dose of corticosteroids and patient is stable or improved clinically (RANO).

  3. Duration of Response (DoR): Parts A and B.

    Time frame: Date of first evidence of a CR or PR to date of objective disease progression or death due to any cause (Up to 25 Months)

    DoR is the time between first evidence of CR or PR and disease progression or death due to any cause.

    RECIST was used for solid tumors and RANO was used for brain tumors.

    • CR is defined as the disappearance of all target lesions (RECIST) and disappearance of all enhancing measurable and non-measurable disease, no new lesions; stable or improved non-enhancing lesions; and patient must be off corticosteroids and stable or improved clinically (RANO).
    • PR is defined as a 30% decrease in the sum of diameters of target lesions (RECIST) and >50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, no new lesions, stable/improved non-enhancing lesions on same or lower dose of corticosteroids and patient is stable or improved clinically (RANO).

  4. Duration of Response (DoR): Part C

    Time frame: Date of first evidence of a CR, PR, or MR to date of objective disease progression or death due to any cause (Up to 25 Months)

    DoR is the time between first evidence of CR, PR or MR and disease progression or death due to any cause.

    CR, PR, and MR was as per International Neuroblastoma Response Criteria (INRC).

    • CR is defined as complete response in all response components: Primary Tumor: <10 mm residual soft tissue primary site and complete resolution of MIBG-avid tumors Soft tissue and bone metastatic response: nonprimary target and nontarget lesions <10 mm and nodes identified as targets decreased to short axis <10mm and MIBG-avid update of nonprimary lesions completely resolved Bone marrow response: no tumor infiltration on reassessment; disappearance of all target lesions;
    • PR is defined as PR in >1 component and all other components are either CR, minimal disease (MD) (bone marrow only), PR (soft tissue or bone), or not involved (NI) and no components with progressive disease (PD).
    • MR is defined PR or CR in >1 component and SD in >1 component and no component with PD

  5. Percentage of Participants With Clinical Benefit Rate (CBR): Part A

    Time frame: Date of first dose to disease progression or death due to any cause (Up to 25 Months)

    The CBR is the percentage of participants with a best response of CR or PR, or Stable Disease (SD) for at least 6 months.

    RECIST was used for solid tumors and RANO was used for brain tumors.

    • CR is defined as the disappearance of all target lesions (RECIST) and disappearance of all enhancing measurable and non-measurable disease, no new lesions; stable or improved non-enhancing lesions; and patient must be off corticosteroids and stable or improved clinically (RANO).
    • PR is defined as a 30% decrease in the sum of diameters of target lesions (RECIST) and >50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, no new lesions, stable/improved non-enhancing lesions on same or lower dose of corticosteroids and patient is stable or improved clinically (RANO).
    • SD is neither sufficient shrinkage nor sufficient increase in the size of the tumor.

  6. Percentage of Participants With CBR: Part B

    Time frame: Date of first dose to disease progression or death due to any cause (Up to 25 Months)

    The CBR is the percentage of participants with a best response of CR or PR, or SD for at least 6 months.

    RECIST was used for solid tumors and RANO was used for brain tumors.

    • CR is defined as the disappearance of all target lesions (RECIST) and disappearance of all enhancing measurable and non-measurable disease, no new lesions; stable or improved non-enhancing lesions; and patient must be off corticosteroids and stable or improved clinically (RANO).
    • PR is defined as a 30% decrease in the sum of diameters of target lesions (RECIST) and >50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, no new lesions, stable/improved non-enhancing lesions on same or lower dose of corticosteroids and patient is stable or improved clinically (RANO).
    • SD is neither sufficient shrinkage nor sufficient increase in the size of the tumor.

  7. Percentage of Participants With Disease Control Rate (DCR): Part A

    Time frame: Date of first dose to measured progressive disease (Up to 25 Months)

    DCR: Percentage of participants with a best overall response of CR, PR, and SD. RECIST was used for solid tumors and RANO was used for brain tumors.

    • CR is defined as the disappearance of all target lesions (RECIST) and disappearance of all enhancing measurable and non-measurable disease, no new lesions; stable or improved non-enhancing lesions; and patient must be off corticosteroids and stable or improved clinically (RANO).
    • PR is defined as a 30% decrease in the sum of diameters of target lesions (RECIST) and >50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, no new lesions, stable/improved non-enhancing lesions on same or lower dose of corticosteroids and patient is stable or improved clinically (RANO).
    • SD is neither sufficient shrinkage nor sufficient increase in the size of the tumor.

  8. Percentage of Participants With DCR: Part B

    Time frame: Date of first dose to measured progressive disease (Up to 25 Months)

    DCR: Percentage of participants with a best overall response of CR, PR, and SD. RECIST was used for solid tumors and RANO was used for brain tumors.

    • CR is defined as the disappearance of all target lesions (RECIST) and disappearance of all enhancing measurable and non-measurable disease, no new lesions; stable or improved non-enhancing lesions; and patient must be off corticosteroids and stable or improved clinically (RANO).
    • PR is defined as a 30% decrease in the sum of diameters of target lesions (RECIST) and >50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, no new lesions, stable/improved non-enhancing lesions on same or lower dose of corticosteroids and patient is stable or improved clinically (RANO).
    • SD is neither sufficient shrinkage nor sufficient increase in the size of the tumor.

  9. Progression-Free Survival (PFS): Part C

    Time frame: Date of first dose to progressive disease or death (Up to 25 Months)

    Progression-free survival is measured as the time from first dose of study drug to progressive disease or death, whichever occurs first. PFS for Part C was reported.

  10. Abemaciclib Tablet Acceptability

    Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (21 Day Cycles)

    Participants were evaluated for abemaciclib acceptability (palatability and ease of administration) by asking a question - " Was it easy or difficult for the study subject to swallow the abemaciclib today?" Participants or their caregivers or both could respond using the following possible answers: Very difficult, difficult, neither easy nor difficult, easy, or very easy.

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Registry information

Official study 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)

Important dates

Study start
2020
Primary completion
2024
Study completion
2025
First posted
Jan 23, 2020
Registry last updated
Mar 2, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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