A Phase 2, Multicenter, Open-label Study to Assess Safety and Preliminary Activity of Eribulin Mesylate in Pediatric Subjects With Relapsed/Refractory Rhabdomyosarcoma (RMS), Non-rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS) and Ewing Sarcoma (EWS)
Overview
- Phase
- Phase 2
- Intervention
- Eribulin mesylate
- Conditions
- Relapsed/Refractory Rhabdomyosarcoma
- Sponsor
- Eisai Inc.
- Enrollment
- 23
- Locations
- 41
- Primary Endpoint
- Percentage of Participants With Objective Response
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age: ≥12 months to \<18 years old at the time of informed consent
- •Diagnosis: Histologically confirmed rhabdomyosarcoma (RMS), non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) (Grade 2 or 3), or Ewing sarcoma (EWS) which is relapsed or refractory (failed front line therapy)
- •The presence of measurable disease meeting the following criteria:
- •At least 1 lesion of ≥1.0 centimeter (cm) in the longest diameter for a non-lymph node or ≥1.5 cm in the short-axis diameter for a lymph node that is serially measurable according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 using computerized tomography/magnetic resonance imaging (CT/MRI).
- •Lesions that have had radiotherapy must show subsequent radiographic evidence of increase in size by at least 20% to be deemed a target lesion.
- •Therapeutic options: Participant's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life.
- •Performance level: Performance score ≥50%. Karnofsky (for participants \>16 years of age) or Lansky (for participants ≤16 years of age). Participants who are unable to walk because of paralysis and/or previous surgeries, but who are in a wheelchair, will be considered ambulatory for the purpose of assessing performance score.
- •Participants must have fully recovered from the acute toxic effects of all prior anticancer therapy and must meet the following minimum duration from prior anticancer directed therapy prior to study drug administration. If, after the required time frame, the numerical eligibility criteria are met, eg, blood count criteria, the participant is considered to have recovered adequately:
- •Cytotoxic chemotherapy or other chemotherapy known to be myelosuppressive: ≥21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea).
- •Anticancer agents not known to be myelosuppressive (eg, not associated with reduced platelet or absolute neutrophil count \[ANC\] counts): ≥7 days after the last dose of agent.
Exclusion Criteria
- •Pregnancy, breastfeeding, contraception: Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic \[β-hCG\] or human chorionic gonadotropin \[hCG\] test with a minimum sensitivity of 25 International Units per Liter \[IU/L\] or equivalent units of β-hCG \[or hCG\]). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
- •Females of childbearing potential (all post pubertal females will be considered to be of childbearing potential unless they have early menopause \[amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause\] or have been sterilized surgically \[ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing\]) who:
- •Do not agree to use a highly effective method of contraception for the entire study period and for 6 months after study drug discontinuation, ie:
- •Total abstinence (if it is their preferred and usual lifestyle);
- •An intrauterine device (IUD) or intrauterine system (IUS);
- •A contraceptive implant;
- •An oral contraceptive (must be on a stable dose of the same oral hormonal contraceptive product for at least 4 weeks before dosing with study drug and for the duration of the study and for 6 months after study drug discontinuation); or
- •Do not have a vasectomized partner with confirmed azoospermia.
- •For sites outside of the European Union (EU), it is permissible that if a highly effective method of contraception is not appropriate or acceptable to the participant, or the participant has commenced/adjusted/changed oral hormonal contraceptive product/dose within 4 weeks prior to study drug administration, then the participant must agree to use a medically acceptable method of contraception, ie, double barrier methods of contraception such as condoms plus diaphragm or cervical/vault cap with spermicide.
- •Males who have not had a successful vasectomy (confirmed azoospermia) or if they and their female partners do not meet the criteria above (ie, not of childbearing potential or practicing highly effective contraception throughout the study period or for 3 months after study drug discontinuation). No sperm donation is allowed during the study period or for 3 months after study drug discontinuation.
Arms & Interventions
Eribulin mesylate 1.4 mg/m^2: NRSTS
Pediatric participants with non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) will receive eribulin mesylate administered as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants will continue study therapy until progression of disease (per RECIST 1.1), intolerable toxicity, or withdrawal of consent.
Intervention: Eribulin mesylate
Eribulin mesylate 1.4 mg/m^2: RMS
Pediatric participants with relapsed/refractory rhabdomyosarcoma (RMS) will receive eribulin mesylate administered as an intravenous (IV) infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 milligrams per meters squared (mg/m\^2). Participants will continue study therapy until progression of disease (per Response Evaluation Criteria In Solid Tumors \[RECIST\] 1.1), intolerable toxicity, or withdrawal of consent.
Intervention: Eribulin mesylate
Eribulin mesylate 1.4 mg/m^2: EWS
Pediatric participants with Ewing sarcoma (EWS) will receive eribulin mesylate administered as an IV infusion on Days 1 and 8 of each 21-day cycle at a dose of 1.4 mg/m\^2. Participants will continue study therapy until progression of disease (per RECIST 1.1), intolerable toxicity, or withdrawal of consent.
Intervention: Eribulin mesylate
Outcomes
Primary Outcomes
Percentage of Participants With Objective Response
Time Frame: From date of randomization up to first documentation of disease progression (PD) or date of death, whichever occurred first (approximately 32 months)
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.
Secondary Outcomes
- Number of Participants With Any Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)(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 Clinically Significant Change From Baseline in Vital Signs Values(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(Baseline up to approximately 32 months)
- Progression-free Survival (PFS)(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 a Shift From Baseline to Worst Post-Baseline Common Terminology Criteria for Adverse Events (CTCAE) Grade in Laboratory Value(From first dose of study drug up to approximately 32 months)
- Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Values(From first dose of study drug up to approximately 32 months)
- Number of Participants With Shift From Baseline to Worst Post-baseline for Karnofsky Performance Status Scores(Baseline up to approximately 32 months)
- Duration of Response (DOR)(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)(From the day of first dose to the day of death, up to approximately 45 months)