Clinical trial NCT04238819: A Study of Abemaciclib (LY2835219) in Combination With Other Anti-Cancer Treatments in Children and Young Adult Participants With Solid Tumors, Including Neuroblastoma
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Relapsed Solid Tumor
Refractory Solid Tumor
Keywords: CDK4
CDK6
Ewing's sarcoma
Neuroblastoma
Recurrent neuroblastoma
Malignant rhabdoid tumor
Rhabdomyosarcoma
Osteosarcoma
Brain tumor
Glioblastoma
Malignant glioma
Diffuse intrinsic pontine glioma
Medulloblastoma
Ependymoma
Solid tumor
High-grade glioma
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2020-01-23
Enrollment: 117
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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 ≥0.2 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.

Primary outcomes:
measure: Number or Participants with Dose Limiting Toxicities (DLTs)
timeFrame: Cycle 1 (21 Day Cycle)
measure: Pharmacokinetics (PK): Mean Steady State Concentrations of Abemaciclib
timeFrame: Cycle 1 through Cycle 3 (21 Day Cycle)
measure: PK: Mean Steady State Concentrations of Irinotecan
timeFrame: Cycle 1 through Cycle 3 (21 Day Cycle)
measure: PK: Mean Steady State Concentrations of Temozolomide
timeFrame: Cycle 1 through Cycle 3 (21 Day Cycle)
measure: Objective Response Rate (ORR): Percentage of Participants with Best Response of Complete Response (CR), Partial Response (PR), or Minimal Response (MR): Part C, only
timeFrame: Baseline through Disease Progression or Death (Estimated up to 24 Months)
Secondary outcomes:
measure: Overall Response Rate (ORR): Percentage of Participants with Best Response of Complete Response (CR) or Partial Response (PR): Parts A and B, only
timeFrame: Baseline through Disease Progression or Death (Estimated up to 24 Months)
measure: Duration of Response (DoR)
timeFrame: 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)
measure: 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
timeFrame: Baseline through Disease Progression or Death Due to Any Cause (Estimated up to 24 Months)
measure: Disease Control Rate (DCR): Percentage of Participants with a Best Overall Response of CR, PR, MR (Part C, only), and Stable Disease (SD)
timeFrame: Baseline through Measured Progressive Disease (Estimated up to 24 Months)
measure: Progression-Free Survival (PFS): Part C, Only
timeFrame: Baseline through Progressive Disease or Death (Estimated up to 24 Months)
measure: Acceptability Questionnaire
timeFrame: Cycle 2 Day 1 (21 Day Cycles)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Los Angeles
country: United States
facility: The Regents of the University of California - Los Angeles (UCLA Pediatrics)
state: California
city: Oakland
country: United States
facility: Kaiser Permanente Oakland
state: California
city: Roseville
country: United States
facility: Kaiser Permanente Roseville
state: California
city: Santa Clara
country: United States
facility: Kaiser Permanente Santa Clara
state: California
city: Indianapolis
country: United States
facility: Riley Hospital for Children at Indiana University Health
state: Indiana
city: Grand Rapids
country: United States
facility: Spectrum Health
state: Michigan
city: New Hyde Park
country: United States
facility: Cohen Children's Medical Center
state: New York
city: Charlotte
country: United States
facility: Atrium Health - Carolinas Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia (CHOP)
state: Pennsylvania
city: Providence
country: United States
facility: Lifespan Cancer Institute
state: Rhode Island
city: Perth
country: Australia
facility: Perth Children's Hospital
state: Western Australia
city: Gent
country: Belgium
facility: UZ Gent
state: Oost-Vlaanderen
city: Lyon
country: France
facility: Centre Leon Berard
state: Rhône
city: Villejuif
country: France
facility: Gustave Roussy
state: Val-de-Marne
city: Paris
country: France
facility: Institut Curie
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
state: Baden-Württemberg
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: Charité Campus Virchow-Klinikum
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli
state: Lazio
city: Chuo Ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
state: Barcelona [Barcelona]
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Niño Jesús
state: Madrid, Comunidad De
city: València
country: Spain
facility: Hospital Universitari i Politecnic La Fe
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: