Clinical Trials /

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

NCT04238819

Description:

The study's purpose is to see if the drug abemaciclib is safe and effective in combination with temozolomide and irinotecan (Part A) and abemaciclib in combination with temozolomide (Part B) in pediatric and young adult participants with relapsed/refractory solid tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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
  • Official Title: A Phase 1b Dose Escalation Study of Abemaciclib in Combination With Temozolomide and Irinotecan (Part A) and Abemaciclib in Combination With Temozolomide (Part B) in Pediatric and Young Adult Patients With Relapsed/Refractory Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 16950
  • SECONDARY ID: I3Y-MC-JPCS
  • SECONDARY ID: 2019-002931-27
  • NCT ID: NCT04238819

Conditions

  • Relapsed Solid Tumor
  • Refractory Solid Tumor

Interventions

DrugSynonymsArms
AbemaciclibLY2835219Dose Escalation: Abemaciclib + Irinotecan + Temozolomide
IrinotecanDose Escalation: Abemaciclib + Irinotecan + Temozolomide
TemozolomideDose Escalation: Abemaciclib + Irinotecan + Temozolomide

Purpose

The study's purpose is to see if the drug abemaciclib is safe and effective in combination with temozolomide and irinotecan (Part A) and abemaciclib in combination with temozolomide (Part B) in pediatric and young adult participants with relapsed/refractory solid tumors.

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation: Abemaciclib + Irinotecan + TemozolomideExperimentalAbemaciclib given orally, irinotecan given intravenously (IV) and temozolomide given orally.
  • Abemaciclib
  • Irinotecan
  • Temozolomide
Dose Expansion: Abemaciclib + Irinotecan + TemozolomideExperimentalAbemaciclib given orally, irinotecan given IV and temozolomide given orally.
  • Abemaciclib
  • Irinotecan
  • Temozolomide
Dose Escalation: Abemaciclib + TemozolomideExperimentalAbemaciclib and temozolomide given orally.
  • Abemaciclib
  • Temozolomide
Dose Expansion: Abemaciclib + TemozolomideExperimentalAbemaciclib and temozolomide given orally.
  • Abemaciclib
  • Temozolomide

Eligibility Criteria

        Inclusion Criteria:

          -  Body weight ≥10 kilograms and body surface area (BSA) ≥0.5 meters squared.

          -  Participants with any relapsed/refractory solid tumor (excluding lymphoma), including
             central nervous system tumors, that have progressed on standard therapies and, in the
             judgment of the investigator, are appropriate candidates for experimental therapy.

          -  A Lansky score ≥50 for participants ≤16 years of age, and 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 serum pregnancy test at baseline
             (within 7 days prior to starting treatment).

          -  Both female and male participants of reproductive potential must agree to use highly
             effective contraceptive precautions (and avoid sperm donation for males) during the
             trial. For abemaciclib, females should use contraception for at least 3 weeks
             following the last abemaciclib dose (males have no restriction for contraceptive use
             following treatment with 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 (within 4 weeks prior to starting study treatment).

          -  Have a personal history of any of the following conditions within the last 12 months:
             syncope of cardiovascular etiology, ventricular tachycardia, ventricular fibrillation,
             or sudden cardiac arrest.

          -  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.

          -  Treated with drugs known to be strong inhibitors or inducers of isoenzyme cytochrome
             P450 3A (CYP3A) and 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.

          -  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 (4 months for studies conducted in Japan).
      
Maximum Eligible Age:18 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number or Participants with Dose Limiting Toxicities (DLTs)
Time Frame:Cycle 1 (21 Day Cycle)
Safety Issue:
Description:Number of Participants with DLTs

Secondary Outcome Measures

Measure:Overall Response Rate (ORR): Percentage of Participants with Best Response of Complete Response (CR) or Partial Response (PR)
Time Frame:Baseline through Disease Progression or Death (Estimated up to 24 Months)
Safety Issue:
Description:ORR: Percentage of Participants with Best Response of CR or PR
Measure:Duration of Response (DoR)
Time Frame:Date of First Evidence of a CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Estimated up to 24 Months)
Safety Issue:
Description:DoR
Measure:Clinical Benefit Rate (CBR): Percentage of Participants With Best Overall Response of CR, PR 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)
Safety Issue:
Description:CBR: Percentage of Participants With Best Overall Response of CR, PR or SD With a Duration of At Least 6 Months
Measure:Disease Control Rate (DCR): Percentage of Participants with a Best Overall Response of CR, PR, and Stable Disease (SD)
Time Frame:Baseline through Measured Progressive Disease (Estimated up to 24 Months)
Safety Issue:
Description:DCR: Percentage of Participants with a Best Overall Response of CR, PR, and SD
Measure:Acceptability Questionnaire
Time Frame:Cycle 2 Day 1 (21 Day Cycles)
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Eli Lilly and Company

Trial Keywords

  • CDK4
  • CDK6
  • Ewing's sarcoma
  • neuroblastoma
  • malignant rhabdoid tumor
  • rhabdomyosarcoma
  • osteosarcoma
  • brain tumor
  • glioblastoma
  • malignant glioma
  • diffuse intrinsic pontine glioma
  • medulloblastoma
  • ependymoma
  • solid tumor

Last Updated

March 16, 2020