This study will be conducted as an assessment of the safety and preliminary activity of eribulin mesylate in pediatric participants with relapsed/refractory rhabdomyosarcoma (RMS), non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), or Ewing sarcoma (EWS) to determine whether each cohort warrants further investigation.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
23
Intravenous infusion
University of Alabama at Birmingham
Birmingham, Alabama, United States
Phoenix Children's Hospital
Phoenix, Arizona, United States
Loma Linda University Cancer Center
Loma Linda, California, United States
Children's Hospital Los Angeles
Los Angeles, California, United States
Southern California Permanente Medical Group
Los Angeles, California, United States
Percentage of Participants With Objective Response
Percentage of participants achieving a best objective response of partial response (PR) or complete response (CR) per RECIST 1.1, by up to 24 weeks after all participants have completed response assessment. Response assessment was determined by investigator. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in the short axis to less than (\<) 10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From date of randomization up to first documentation of disease progression (PD) or date of death, whichever occurred first (approximately 32 months)
Progression-free Survival (PFS)
PFS was defined as the time from the first dose date to the date of PD or date of death (whichever occurred first). PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions was also considered progression). Data for this secondary endpoint was collected and analyzed up to the primary completion date (PCD). As there was no further data collected, therefore data is reported till PCD only.
Time frame: From the time from the first dose date to the date of disease progression (PD) or date of death, whichever occurred first (up to approximately 32 months)
Number of Participants With Any Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in participant administered with an investigational product. An SAE was any untoward medical occurrence that at any dose: resulted in death; life threatening; requires participant hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug). A treatment-emergent adverse event (TEAE) was defined as an AE that emerges during treatment, having been absent at pretreatment (Baseline) or (1) reemerges during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or (2) worsens in severity during treatment relative to the pretreatment state, when the AE is continuous.
Time frame: From date of administration of first dose up to 28 days after the last dose, or until resolution, whichever came first (up to approximately 45 months)
Number of Participants With a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value
Laboratory results were graded using CTCAE Version 4.03. As per CTCAE, Grade 1 scales as Mild; Grade 2 scales as Moderate; Grade 3 scales as severe or medically significant but not immediately life threatening; Grade 4 scales as life-threatening consequences. Data for this secondary endpoint was collected and analyzed up to the PCD. As there was no further data collected, therefore data is reported till PCD only.
Time frame: From first dose of study drug up to approximately 32 months
Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Values
Data for this secondary endpoint was collected and analyzed up to the PCD. As there was no further data collected, therefore data is reported till PCD only.
Time frame: From first dose of study drug up to approximately 32 months
Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values
Data for this secondary endpoint was collected and analyzed up to the PCD. As there was no further data collected, therefore data is reported till PCD only.
Time frame: From first dose of study drug up to approximately 32 months
Number of Participants With Shift From Baseline to Worst Post-baseline for Lansky Play-performance Scale
Reduced activities of daily living was assessed using the Lansky Play Performance Scale, where 100=fully active; 90=minor restrictions in strenuous physical activity; 80=active, gets tired more quickly; 70=greater restriction of play, less time spent in play activity; 60=up and around, active play minimal; quieter activities; 50=lying around much of the day; no active playing, all quiet play and activities; 40=mainly in bed; quiet activities; 30=bedbound; needs assistance even for quiet play; 20=sleeps often; play limited to very passive activities; 10=doesn't play or get out of bed; 5=unresponsive 0=dead. Data for this secondary endpoint was collected and analyzed up to the PCD. As there was no further data collected, therefore data is reported till PCD only.
Time frame: Baseline up to approximately 32 months
Number of Participants With Shift From Baseline to Worst Post-baseline for Karnofsky Performance Status Scores
Karnofsky performance status assessed as best and worst score change from baseline using Karnofsky performance criteria.Score classified participants based on functional impairment. Ranges from 0-100, lower score, worst survival for most serious illnesses, 100=normal;no complaints;no evidence of disease;90=able to carry on normal activity with effort,minor sign or symptoms of disease;80=normal activity with effort;some sign or symptoms of disease;70= cares for self;unable to carry on normal activity or do active work;60=requires occasional assistance,but able to care for most personal needs;50=requires considerable assistance;frequent medical care;40=disabled;requires special care; assistance;30=severely disabled;hospitalization indicated,although death is not imminent;20=very sick;hospitalization; 10=moribund;fatal processes progressively worsening;0=dead.Data for this endpoint was collected;analyzed up to PCD. As no further data collected, therefore data is reported till PCD only.
Time frame: Baseline up to approximately 32 months
Duration of Response (DOR)
DOR was defined as the time from the first date of documented PR or CR to the date of disease progression or date of death (whichever occurred first). CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in the short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study). Data for this secondary endpoint was collected and analyzed up to the PCD. As there was no further data collected, therefore data is reported till PCD only.
Time frame: From day of first documentation of PR or CR to the day of disease progression or death (up to approximately 32 months)
Overall Survival (OS)
OS was defined as the time from the first dose date to the date of death.
Time frame: From the day of first dose to the day of death, up to approximately 45 months
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Children's Hospital of Orange County
Orange, California, United States
Rady Children's Hospital- San Diego
San Diego, California, United States
Connecticut Children's Medical Center
Hartford, Connecticut, United States
Nemours / A.I. duPont Hospital for Children
Wilmington, Delaware, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
...and 31 more locations