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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
23
Eribulin mesylate will be administered intravenously on Days 1 and 8 of each 21-day cycle.
Children's Hospital of Alabama
Birmingham, Alabama, United States
Childrens Hospital of Orange County
Orange, California, United States
UCSF Medical Center-Parnassus
San Francisco, California, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, United States
Riley Hospital for Children
Indianapolis, Indiana, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, United States
University of Minnesota Cancer Center-Fairview
Minneapolis, Minnesota, United States
Washington University School of Medicine
St Louis, Missouri, United States
Columbia University Medical Center
New York, New York, United States
...and 8 more locations
Maximum Tolerated Dose (MTD) of Eribulin Mesylate
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.
Time frame: First dose of study drug (Baseline) up to Cycle 1 Day 21
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
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.
Time frame: 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 Change From Baseline in Clinical Laboratory Values
Time frame: 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
Time frame: 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 Electrocardiogram (EKG)
Time frame: First dose of study drug (Baseline) up to 30 days after last dose of study drug (Cycle 8 Day 38)
T1/2: Terminal Half-life for Eribulin Mesylate
Time frame: Day 1 predose and at 10, 30 minutes, 1, 2, 4, 6, 24, 48, 72, 96 or 120 hours post-dose
Cmax: Maximum Observed Plasma Concentration for Eribulin Mesylate
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Day 1 predose and at 10, 30 minutes, 1, 2, 4, 6, 24, 48, 72, 96 or 120 hours post-dose
Number of Participants With Best Overall Response
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.
Time frame: First dose of study drug (Baseline) up to approximately Cycle 8 (21-days treatment cycle)
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