A Phase 1/2, Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), Recommended Phase 2 Dose (RP2D), and Efficacy of Lurbinectedin Monotherapy in Pediatric Participants With Previously Treated Solid Tumors Followed by Expansion to Assess Efficacy and Safety in Pediatric and Young Adult Participants With Relapsed/Refractory Ewing Sarcoma.
Summary
This study is conducted in two phases. The phase 1 portion of the study evaluates the safety, tolerability, pharmacokinetics (PK), recommended phase 2 dose (RP2D), and effectiveness of lurbinectedin monotherapy in pediatric participants with previously treated solid tumors. This is followed by the phase 2 portion, to further assess the effectiveness and safety in pediatric and young adult participants with recurrent/refractory Ewing sarcoma.
Arms & interventions
- DrugLurbinectedin
Administered as intravenous (IV) infusion once every 3 weeks (Q3W)
Outcome measures
Primary
Phase 1: Number of Participants Experiencing Dose-limiting Toxicities (DLTs)
Time frame: From the first dose through end of Cycle 1 (21 days).
Phase 1: Number of Participants Experiencing Serious Adverse Events (SAEs) and Treatment Emergent Adverse Events (TEAEs)
Time frame: Post-baseline (Day 1) up to approximately 31 months.
Phase 1: Number of Participants With Dose Modifications
Time frame: Post-baseline (Day 1) up to approximately 31 months.
Phase 1: Number of Participants Who Discontinued Study Intervention Due to TEAEs
Time frame: Post-baseline (Day 1) up to approximately 31 months.
Phase 2: Objective Response Rate (ORR) Based on Investigator Assessment (IA)
Time frame: Day -28 up to a total of 13 months postdose.
Secondary
Phase 1: Plasma Concentration of Lurbinectedin
Time frame: Day 1: Predose up to approximately 168 hours postdose; Days 16, 31, 46: Predose up to approximately 5 minutes postdose.
Phase 1: Objective Response Rate (ORR) Based on Investigator Assessment (IA)
Time frame: Day -28 up to a total of 31 months postdose.
Phase 1: Progression-Free Survival (PFS) Based on Investigator Assessment (IA)
Time frame: Day -28 up to a total of 31 months postdose.
Phase 1: Duration of Response (DOR) in Participants with Confirmed Complete Response (CR) or Partial Response (PR)
Time frame: Day -28 up to a total of 31 months postdose.
Phase 1: Disease Control Rate (DCR)
Time frame: Day -28 up to a total of 31 months postdose.
Phase 1: Clinical Benefit Rate (CBR) With Stable Disease (SD) for At Least 12 Weeks
Time frame: Day -28 up to a total of 31 months postdose.
Phase 1: Overall Survival (OS)
Time frame: Post-baseline (Day 1) up to 31 months postdose.
Phase 1: Change From Baseline in Respiratory Rate
Time frame: Post-baseline (Day 1) up to approximately 31 months.
Phase 1: Change From Baseline in Pulse Rate
Time frame: Post-baseline (Day 1) up to approximately 31 months.
Phase 1: Change From Baseline in Blood Pressure
Time frame: Post-baseline (Day 1) up to approximately 31 months.
Phase 1: Change From Baseline in Weight
Time frame: Post-baseline (Day 1) up to approximately 31 months.
Phase 1: Change from Baseline in Platelet Count
Time frame: Post-baseline (Day 1) up to approximately 31 months.
Phase 1: Change from Baseline in Red Blood Cell Count
Time frame: Post-baseline (Day 1) up to approximately 31 months.
Phase 1: Change from Baseline in Hemoglobin
Time frame: Post-baseline (Day 1) up to approximately 31 months.
Phase 1: Change from Baseline in Differential White Blood Cell Count
Time frame: Post-baseline (Day 1) up to approximately 31 months.
Phase 1: Change From Baseline in AST/ALT Levels
Time frame: Post-baseline (Day 1) up to approximately 31 months.
Phase 1: Change From Baseline in Creatinine Levels
Time frame: Post-baseline (Day 1) up to approximately 31 months.
Phase 1: Change From Baseline in CPK Levels
Time frame: Post-baseline (Day 1) up to approximately 31 months.
Phase 2: Plasma Concentration of Lurbinectedin
Time frame: Day 1: Predose up to approximately 168 hours postdose; Days 16, 31, 46: Predose up to approximately 5 minutes postdose.
Phase 2: Number of Participants Experiencing Serious Adverse Events (SAEs) and Treatment-emergent Adverse Events (TEAEs)
Time frame: Post-baseline (Day 1) up to approximately 13 months.
Phase 2: Number of Participants With Dose Modifications
Time frame: Post-baseline (Day 1) up to approximately 13 months.
Phase 2: Number of Participants Who Discontinued Study Intervention Due to TEAEs
Time frame: Post-baseline (Day 1) up to approximately 13 months.
Phase 2: Progression-Free Survival (PFS) Based on IA
Time frame: Day -28 up to a total of 13 months postdose.
Phase 2: Duration of Response (DOR) in Participants with Confirmed Complete Response (CR) or Partial Response (PR)
Time frame: Day -28 up to a total of 13 months postdose.
Phase 2: Disease Control Rate (DCR)
Time frame: Day -28 up to a total of 13 months postdose.
Phase 2: Clinical Benefit Rate (CBR) With Stable Disease (SD) for At Least 12 Weeks
Time frame: Day -28 up to a total of 13 months postdose.
Phase 2: Overall Survival (OS)
Time frame: Post-baseline (Day 1) up to 13 months postdose.
Phase 2: Change From Baseline in Respiratory Rate
Time frame: Post-baseline (Day 1) up to approximately 13 months.
Phase 2: Change From Baseline in Pulse Rate
Time frame: Post-baseline (Day 1) up to approximately 13 months.
Phase 2: Change From Baseline in Blood Pressure
Time frame: Post-baseline (Day 1) up to approximately 13 months.
Phase 2: Change From Baseline in Weight
Time frame: Post-baseline (Day 1) up to approximately 13 months.
Phase 2: Change From Baseline in Platelet Count
Time frame: Post-baseline (Day 1) up to approximately 13 months.
Phase 2: Change From Baseline in Red Blood Cell Count
Time frame: Post-baseline (Day 1) up to approximately 13 months.
Phase 2: Change From Baseline in Hemoglobin
Time frame: Post-baseline (Day 1) up to approximately 13 months.
Phase 2: Change From Baseline in Differential White Blood Cell Count
Time frame: Post-baseline (Day 1) up to approximately 13 months.
Phase 2: Change From Baseline in AST/ALT Levels
Time frame: Post-baseline (Day 1) up to approximately 13 months.
Phase 2: Change From Baseline in Creatinine Levels
Time frame: Post-baseline (Day 1) up to approximately 13 months.
Phase 2: Change From Baseline in CPK Levels
Time frame: Post-baseline (Day 1) up to approximately 13 months.
Eligibility criteria
Study locations (14)
Children's Hospital of Los Angeles
Los Angeles, California, 90027
Lucile Packard Children's Hospital
Palo Alto, California, 94304
Children's National Hospital
Washington D.C., District of Columbia, 20010
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701
Children's Healthcare of Atlanta at Arthur M. Blank Hospital
Atlanta, Georgia, 30329
Johns Hopkins University
Baltimore, Maryland, 21238
Corewell Health
Grand Rapids, Michigan, 49503
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Nationwide Children's Hospital
Columbus, Ohio, 43205
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Children's Health Dallas
Dallas, Texas, 75235
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030