A Study of Abemaciclib (LY2835219) in Combination With Other Anti-Cancer Treatments in Children and Young Adult Participants With Solid Tumors, Including Neuroblastoma
- Conditions
- Interventions
- Registration Number
- NCT04238819
- Lead Sponsor
- 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. For each participant, the study is estimated to last up to 2 years.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 117
-
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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Dose Escalation: Abemaciclib + Irinotecan + Temozolomide Temozolomide Abemaciclib given orally, irinotecan given intravenously (IV) and temozolomide given orally. Dose Expansion: Abemaciclib + Irinotecan + Temozolomide Abemaciclib Abemaciclib given orally, irinotecan given IV and temozolomide given orally. Dose Expansion: Abemaciclib + Irinotecan + Temozolomide Temozolomide Abemaciclib given orally, irinotecan given IV and temozolomide given orally. Dose Expansion: Abemaciclib + Temozolomide Temozolomide Abemaciclib and temozolomide given orally. Part C Stage 2: Abemaciclib in Combination with Dinutuximab, GM-CSF, Irinotecan, and Temozolomide GM-CSF Abemaciclib given orally, dinutuximab given IV, GM-CSF given subQ, irinotecan given IV and temozolomide given orally or IV. Dose Escalation: Abemaciclib + Irinotecan + Temozolomide Abemaciclib Abemaciclib given orally, irinotecan given intravenously (IV) and temozolomide given orally. Dose Escalation: Abemaciclib + Irinotecan + Temozolomide Irinotecan Abemaciclib given orally, irinotecan given intravenously (IV) and temozolomide given orally. Dose Expansion: Abemaciclib + Irinotecan + Temozolomide Irinotecan Abemaciclib given orally, irinotecan given IV and temozolomide given orally. Dose Escalation: Abemaciclib + Temozolomide Abemaciclib Abemaciclib and temozolomide given orally. Dose Escalation: Abemaciclib + Temozolomide Temozolomide Abemaciclib and temozolomide given orally. Dose Expansion: Abemaciclib + Temozolomide Abemaciclib Abemaciclib and temozolomide given orally. Part C Stage 1: Abemaciclib in Combination with Dinutuximab, GM-CSF, Irinotecan, and Temozolomide Irinotecan 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. Part C Stage 1: Abemaciclib in Combination with Dinutuximab, GM-CSF, Irinotecan, and Temozolomide Abemaciclib 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. Part C Stage 1: Abemaciclib in Combination with Dinutuximab, GM-CSF, Irinotecan, and Temozolomide 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. Part C Stage 1: Abemaciclib in Combination with Dinutuximab, GM-CSF, Irinotecan, and Temozolomide GM-CSF 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. Part C Stage 1: Abemaciclib in Combination with Dinutuximab, GM-CSF, Irinotecan, and Temozolomide Dinutuximab 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. Part C Stage 2: Abemaciclib in Combination with Dinutuximab, GM-CSF, Irinotecan, and Temozolomide Abemaciclib Abemaciclib given orally, dinutuximab given IV, GM-CSF given subQ, irinotecan given IV and temozolomide given orally or IV. Part C Stage 2: Abemaciclib in Combination with Dinutuximab, GM-CSF, Irinotecan, and Temozolomide Irinotecan Abemaciclib given orally, dinutuximab given IV, GM-CSF given subQ, irinotecan given IV and temozolomide given orally or IV. Part C Stage 2: Abemaciclib in Combination with Dinutuximab, GM-CSF, Irinotecan, and Temozolomide Temozolomide Abemaciclib given orally, dinutuximab given IV, GM-CSF given subQ, irinotecan given IV and temozolomide given orally or IV. Part C Stage 2: Abemaciclib in Combination with Dinutuximab, GM-CSF, Irinotecan, and Temozolomide Dinutuximab Abemaciclib given orally, dinutuximab given IV, GM-CSF given subQ, irinotecan given IV and temozolomide given orally or IV.
- Primary Outcome Measures
Name Time Method PK: Mean Steady State Concentrations of Irinotecan Cycle 1 through Cycle 3 (21 Day Cycle) PK: Mean Steady State Concentrations of Irinotecan
Number or Participants with Dose Limiting Toxicities (DLTs) Cycle 1 (21 Day Cycle) Number of Participants with DLTs
Pharmacokinetics (PK): Mean Steady State Concentrations of Abemaciclib Cycle 1 through Cycle 3 (21 Day Cycle) PK: Mean Steady State Concentrations of Abemaciclib
PK: Mean Steady State Concentrations of Temozolomide Cycle 1 through Cycle 3 (21 Day Cycle) PK: Mean Steady State Concentrations of Temozolomide
Objective Response Rate (ORR): Percentage of Participants with Best Response of Complete Response (CR), Partial Response (PR), or Minimal Response (MR): Part C, only 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
Name Time Method 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 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
Disease Control Rate (DCR): Percentage of Participants with a Best Overall Response of CR, PR, MR (Part C, only), and Stable Disease (SD) 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
Duration of Response (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) DoR
Progression-Free Survival (PFS): Part C, Only Baseline through Progressive Disease or Death (Estimated up to 24 Months) PFS
Acceptability Questionnaire 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
Overall Response Rate (ORR): Percentage of Participants with Best Response of Complete Response (CR) or Partial Response (PR): Parts A and B, only 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)
Trial Locations
- Locations (25)
Perth Children's Hospital
🇦🇺Perth, Western Australia, Australia
National Cancer Center Hospital
🇯🇵Chuo Ku, Tokyo, Japan
UZ Gent
🇧🇪Gent, Oost-Vlaanderen, Belgium
Gustave Roussy
🇫🇷Villejuif, Val-de-Marne, France
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
The Regents of the University of California - Los Angeles (UCLA Pediatrics)
🇺🇸Los Angeles, California, United States
Riley Hospital for Children at Indiana University Health
🇺🇸Indianapolis, Indiana, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Children's Hospital of Philadelphia (CHOP)
🇺🇸Philadelphia, Pennsylvania, United States
Kaiser Permanente Oakland
🇺🇸Oakland, California, United States
Kaiser Permanente Roseville
🇺🇸Roseville, California, United States
Kaiser Permanente Santa Clara
🇺🇸Santa Clara, California, United States
Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
Cohen Children's Medical Center
🇺🇸New Hyde Park, New York, United States
Atrium Health - Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
Lifespan Cancer Institute
🇺🇸Providence, Rhode Island, United States
Centre Leon Berard
🇫🇷Lyon, Rhône, France
Institut Curie
🇫🇷Paris, France
Universitaetsklinikum Heidelberg
🇩🇪Heidelberg, Baden-Württemberg, Germany
Universitaetsklinikum Essen
🇩🇪Essen, Nordrhein-Westfalen, Germany
Charité Campus Virchow-Klinikum
🇩🇪Berlin, Germany
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Barcelona [Barcelona], Spain
Fondazione Policlinico Universitario Agostino Gemelli
🇮🇹Roma, Lazio, Italy
Hospital Infantil Universitario Niño Jesús
🇪🇸Madrid, Madrid, Comunidad De, Spain
Hospital Universitari i Politecnic La Fe
🇪🇸València, Spain