This is a Phase 1 Study of Eribulin Mesylate in Pediatric Participants With Recurrent or Refractory Solid Tumors (Excluding [Central Nervous System] CNS), Including Lymphomas
- Registration Number
- NCT02171260
- Lead Sponsor
- Eisai Inc.
- Brief Summary
This is a Phase 1 study of eribulin mesylate in pediatric participants with recurrent or refractory solid tumors (excluding CNS), including lymphomas. Eribulin mesylate will be administered intravenously, once per day on Days 1 and 8 of a 21-day cycle. This study aims to determine the maximum tolerated dose (MTD) and/or the Recommended Phase 2 Dose (RP2D) of this regimen in Part A1 (participants greater than or equal to \[\>=\] 12 months and less than \[\<\] 18 years). Part A2 will enroll infants (greater than \[\>\] 6 months and \<12 months) one dose level behind the dose level at which participants in Part A1 are enrolling, in order to maximize safety for infant participants. Additionally, this study aims to describe the toxicities and the pharmacokinetics of eribulin mesylate when administered to children. In a preliminary manner, the antitumor effect of eribulin mesylate will also be described.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 23
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Eribulin Mesylate Eribulin Mesylate Eribulin mesylate will be administered intravenously on Days 1 and 8 of each 21-day cycle. A cycle of therapy is considered to be 21 days. The starting dose for eribulin mesylate will be at 1.1 milligram per square meter (mg/m\^2) (Dose Level 1), which is approximately 80% of the adult MTD, and will be escalated up to no more than 2.2 mg/m\^2.
- Primary Outcome Measures
Name Time Method Number of Participants With Clinically Significant Electrocardiogram (EKG) First dose of study drug (Baseline) up to 30 days after last dose of study drug (Cycle 8 Day 38) Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) First dose of study drug (Baseline) up to 30 days after last dose of study drug (Cycle 8 Day 38) TEAEs were defined as those adverse events (AEs) that occurred (or worsened, if present at Baseline) after the first dose of study drug through 30 days after the last dose of study drug. An AE was defined as any untoward medical occurrence in a participants or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with medicinal product. A SAE was defined as any AE if it resulted in death or life-threatening AE or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or was a congenital anomaly/birth defect.
T1/2: Terminal Half-life for Eribulin Mesylate Day 1 predose and at 10, 30 minutes, 1, 2, 4, 6, 24, 48, 72, 96 or 120 hours post-dose Maximum Tolerated Dose (MTD) of Eribulin Mesylate First dose of study drug (Baseline) up to Cycle 1 Day 21 MTD: maximum dose at which \<one third participants had DLT in Cycle 1. DLT: Grade 3/4 drug-related non hematological toxicity (except Grade 3 nausea, vomiting of \<3 days, Grade 3 liver enzyme elevation with alanine transaminase/aspartate transaminase and gamma glutamyl transferase that returned to Grade \<=1 or baseline prior to next dose; Grade 3 fever, infection, hypophosphatemia, hypokalemia, hypocalcemia/hypomagnesemia responsive to oral supplementation). Non-hematological toxicity causing \>=14 days delay between treatment cycles. Haematological DLTs included: Grade 4 neutropenia/platelets\<75,000/mm\^3 on Day 8 that does not resolve to absolute neutrophil count \>=750/mm\^3 and platelets\>=75,000/mm\^3 by Day 11, neutropenia for \>7 days; platelet count \<25,000/mm\^3, or required platelet transfusion, on 2 separate days within 7-day period;Grade 3 thrombocytopenia complicated by bleeding and/or required platelet transfusion;myelosuppression causing \>14 days delay between treatment cycles.
Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Values First dose of study drug (Baseline) up to 30 days after last dose of study drug (Cycle 8 Day 38) Number of Participants With Clinically Significant Vital Sign Values First dose of study drug (Baseline) up to 30 days after last dose of study drug (Cycle 8 Day 38) Cmax: Maximum Observed Plasma Concentration for Eribulin Mesylate Day 1 predose and at 10, 30 minutes, 1, 2, 4, 6, 24, 48, 72, 96 or 120 hours post-dose Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Eribulin Mesylate Day 1 predose and at 10, 30 minutes, 1, 2, 4, 6, 24, 48, 72, 96 or 120 hours post-dose AUC 0-t: Area Under the Concentration-time Curve From Zero (Pre-dose) to Time of Last Quantifiable Concentration for Eribulin Mesylate Day 1 predose and at 10, 30 minutes, 1, 2, 4, 6, 24, 48, 72, 96 or 120 hours post-dose AUC 0-inf: Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time for Eribulin Mesylate Day 1 predose and at 10, 30 minutes, 1, 2, 4, 6, 24, 48, 72, 96 or 120 hours post-dose CL: Clearance for Eribulin Mesylate Day 1 predose and at 10, 30 minutes, 1, 2, 4, 6, 24, 48, 72, 96 or 120 hours post-dose Vd: Volume of Distribution for Eribulin Mesylate Day 1 predose and at 10, 30 minutes, 1, 2, 4, 6, 24, 48, 72, 96 or 120 hours post-dose
- Secondary Outcome Measures
Name Time Method Number of Participants With Best Overall Response First dose of study drug (Baseline) up to approximately Cycle 8 (21-days treatment cycle) Best Overall Response (BOR): best response recorded from start of study treatment until disease progression (PD) or recurrence based on response evaluation criteria in solid tumors (RECIST) version 1.1 for target and non-target lesions. Participants with evaluable disease were also eligible for assessment.
Trial Locations
- Locations (18)
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Childrens Hospital of Orange County
🇺🇸Orange, California, United States
Children's Hospital of Alabama
🇺🇸Birmingham, Alabama, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
University of Minnesota Cancer Center-Fairview
🇺🇸Minneapolis, Minnesota, United States
Children's Healthcare of Atlanta - Egleston
🇺🇸Atlanta, Georgia, United States
UCSF Medical Center-Parnassus
🇺🇸San Francisco, California, United States
C S Mott Children's Hospital
🇺🇸Ann Arbor, Michigan, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Childrens Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Midwest Children's Cancer Center
🇺🇸Milwaukee, Wisconsin, United States
Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States