Study Evaluating the Safety and Efficacy of Eribulin Mesilate in Combination With Irinotecan Hydrochloride in Children With Refractory or Recurrent Solid Tumors

• ClinicalTrials.gov Identifier: NCT03245450
• Recruitment Status: Completed
• First Posted: August 10, 2017
• Results First Posted: June 28, 2022
• Last Update Posted: June 28, 2022
• Sponsor: Eisai Inc.
• Information provided by (Responsible Party): Eisai Inc.

Tracking Information

• First Submitted Date: August 8, 2017
• First Posted Date: August 10, 2017
• Results First Submitted Date: May 16, 2022
• Results First Posted Date: June 28, 2022
• Last Update Posted Date: June 28, 2022
• Actual Study Start Date: March 5, 2018
• Actual Primary Completion Date: May 17, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 16, 2022)

• Phase 1: Recommended Phase 2 Dose (RP2D) of Eribulin Mesilate in Combination With Irinotecan Hydrochloride [ Time Frame: First dose of study drug up to Cycle 1 (Cycle length=21 days) ]
  The RP2D was evaluated based on a review of the outcomes of safety (including dose limiting toxicities [DLTs]), tumor assessments, and pharmacokinetic (PK) in Phase 1 by investigators and the study team.
• Phase 2: Objective Response Rate (ORR) [ Time Frame: From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or up to approximately 2 years 4 months ]
  ORR was defined as the percentage of participants achieving best overall response (BOR) of confirmed partial response (PR) or complete response (CR) determined by investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as disappearance of all target and non-target lesions. All pathological (whether target or non-target) must have a reduction in their short axis less than (<) 10 millimeter (mm). PR was at least a 30 percent (%) decrease in the sum of diameter (SOD) of target lesions, taking as reference the baseline sum diameters.

Original Primary Outcome Measures (submitted: August 8, 2017)

• Phase 1: Maximum tolerated dose (MTD) of eribulin mesilate in combination with irinotecan hydrochloride in pediatric participants with relapsed/refractory extra-cranial solid tumors [ Time Frame: Up to 36 months ]
  The MTD is defined as the highest dose level at which less than one-third of participants experience a dose-limiting toxicity (DLT [side effects that prevent a dose increase]) during Cycle 1 of the therapy.
• Phase 1: Recommended phase 2 dose (RP2D) of eribulin mesilate in combination with irinotecan hydrochloride in pediatric participants with relapsed/refractory extra-cranial solid tumors [ Time Frame: Up to 36 months ]
  The RP2D is determined based on the MTD. The MTD is defined as the highest dose level at which less than one-third of participants experience a DLT (side effects that prevent a dose increase) during Cycle 1 of the therapy.
• Phase 2: Objective response rate (ORR) [ Time Frame: Up to 36 months ]
  ORR is defined as the percentage of participants achieving the best overall response of confirmed partial response (PR) or complete response (CR), as determined by investigator review.

Current Secondary Outcome Measures (submitted: May 16, 2022)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: From first dose of study drug up to approximately 2 years 4 months ]
  A TEAE was defined as an AE that emerged during treatment, having been absent at pretreatment, or reemerged during treatment, having been present at pre-treatment (baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment.
• Number of Participants With Serious Adverse Event (SAE) [ Time Frame: Up to approximately 2 years and 4 months ]
  SAE was defined as any untoward medical occurrence at any dose 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.
• Phase 1, Cmax: Maximum Observed Plasma Concentration of Eribulin, Irinotecan and Its Active Metabolite SN-38 [ Time Frame: For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan and its metabolite, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days) ]
• Phase 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Eribulin, Irinotecan and Its Active Metabolite SN-38 [ Time Frame: For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan and its metabolite, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days) ]
• Phase 1, T1/2: Half-life of Eribulin, Irinotecan and Its Active Metabolite SN-38 [ Time Frame: For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan and its metabolite, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days) ]
  Half-life for irinotecan and metabolite SN-38 could not be estimated for phase 1:schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 20 mg/m^2 and phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 40 mg/m^2 arm as the slope of the terminal phase of the concentration-time profiles could not be determined.
• Phase 1, Total Clearance (CL) of Eribulin and Irinotecan [ Time Frame: For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days) ]
  CL for irinotecan could not be estimated for phase 1:schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 20 mg/m^2 and phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 40 mg/m^2 arm because it was not possible to calculate half-life as the slope of the terminal phase of the concentration-time profiles could not be determined.
• Phase 1, Volume of Distribution (Vz) of Eribulin and Irinotecan [ Time Frame: For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days) ]
  Vz for irinotecan could not be estimated for phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 20 mg/m^2 and phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 40 mg/m^2 arm because it was not possible to calculate half-life as the slope of the terminal phase of the concentration-time profiles could not be determined.
• Phase 1, AUC(0-t): Area Under the Concentration-time Curve From Zero (Pre-dose) to Time of Last Quantifiable Concentration of Eribulin, Irinotecan and Its Active Metabolite SN-38 [ Time Frame: For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan and its metabolite, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days) ]
• Phase 1, AUC(0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Eribulin, Irinotecan and Its Active Metabolite SN-38 [ Time Frame: For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan and its metabolite, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days) ]
  AUC(0-inf) for irinotecan and metabolite SN-38 could not be estimated for phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 20 mg/m^2 and phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 40 mg/m^2 arm because it was not possible to calculate half-life as the slope of the terminal phase of the concentration-time profiles could not be determined.
• Phase 2: Progression Free Survival (PFS) [ Time Frame: From the date of first dose to the date of first documentation of PD, or date of death, whichever occurred first up to approximately 2 years 4 months ]
  PFS was defined as the time from date of first dose to the date of disease progression (PD). PFS was assessed based on the investigators' assessments utilizing RECIST 1.1. PD was defined as at least 20% increase or 5 mm increase in the sum of diameters of target lesions recorded since the treatment started or the appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan-Meier method.
• Phase 2: Clinical Benefit Rate (CBR) [ Time Frame: From the date of first dose to the date of first documentation of PD, or date of death, whichever occurred first up to approximately 2 years 4 months ]
  CBR was defined as the percentage of participants with BOR of CR, PR, or durable stable disease (SD) based on RECIST 1.1 (durable SD was defined as SD with duration of greater than [>] 11 weeks). CR was defined as disappearance of all target and non-target lesions. All pathological (whether target or non-target) must have a reduction in their short axis <10 mm. PR was defined as at least 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters.
• Model Predicted Apparent Total Body Clearance (CL) of Eribulin [ Time Frame: Cycle 1 Day 1: 0.5-120 hours after eribulin infusion; Cycle 1 Day 8: pre-dose and at the end of the eribulin infusion (cycle length=21 days) ]
  Per the planned PK analysis, PK samples were collected and analyzed using a population PK approach to estimate PK parameters. Eribulin plasma concentration data from this study were pooled from studies (NCT00069264, NCT00069277, NCT00326950, NCT00706095, NCT01000376, NCT01106248, NCT02171260, NCT00413192, NCT01458249, NCT03441360 and NCT01327885), and a population PK model was applied to the pooled dataset. The data presented are the CL parameter estimates, with Measure Type "Number" defining the eribulin PK model. They are population PK model predictions and have been estimated using non-linear mixed effects model.
• Volume of Distribution Estimates From the Population PK Model for Eribulin [ Time Frame: Cycle 1 Day 1: 0.5-120 hours after eribulin infusion; Cycle 1 Day 8: pre-dose and at the end of the eribulin infusion (cycle length=21 days) ]
  Per the planned PK analysis, PK samples were collected and analyzed using a population PK approach to estimate PK parameters. Eribulin plasma concentration data from this study were pooled from studies (NCT00069264, NCT00069277, NCT00326950, NCT00706095, NCT01000376, NCT01106248, NCT02171260, NCT00413192, NCT01458249, NCT03441360 and NCT01327885), and a population PK model was applied to the pooled dataset. Data presented are the volume of distribution of the central compartment (V1), volume of distribution of the first peripheral compartment (V2), and volume of distribution of the second peripheral compartment (V3) parameter estimates with Measure Type "Number" defining the eribulin PK model. They are population PK model predictions and have been estimated using non-linear mixed effects model.

Original Secondary Outcome Measures (submitted: August 8, 2017)

• Phase 1 and Phase 2: Number of participants with any treatment-emergent (TE) serious adverse event (SAE) [ Time Frame: Up to 36 months ]
  An SAE is any untoward medical occurrence that at any dose: results in death; is life threatening (ie, the participant was at immediate risk of death from the adverse event [AE] as it occurred; this does not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug). A TEAE is 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.
• Phase 1 and Phase 2: Number of participants with any TEAE [ Time Frame: Up to 36 months ]
  An AE is any untoward medical occurrence in a participant or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with the medicinal product. A TEAE is 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.
• Phase 1: Mean value of maximum observed plasma concentration (Cmax) [ Time Frame: Irinotecan (its metabolite) and eribulin: Cycle 1, Day 1 at the end of irinotecan and eribulin infusion, then at 1, 2, 4, 6, and 24 hours post eribulin infusion. Eribulin alone: 48, 72, 96, and 120 hours post eribulin infusion. ]
  Cmax is the highest concentration of drug in the blood that is measured after a dose.
• Phase 2: Mean value of Cmax [ Time Frame: Eribulin assay: Cycle 1, Day 1 (at the end of the infusion, 0.5 to 6 hours and 24 to 120 hours after eribulin infusion) and on Cycle 1, Day 8 (pre-dose of eribulin and at the end of the infusion). ]
  Cmax is the highest concentration of drug in the blood that is measured after a dose.
• Phase 1: Mean value of time of maximum observed concentration following drug administration (tmax) [ Time Frame: Irinotecan (its metabolite) and eribulin: Cycle 1, Day 1 at the end of irinotecan and eribulin infusion, then at 1, 2, 4, 6, and 24 hours post eribulin infusion. Eribulin alone: 48, 72, 96, and 120 hours post eribulin infusion. ]
  Tmax is the time to the highest concentration of drug in the blood that is measured after a dose.
• Phase 2: Mean value of tmax [ Time Frame: Eribulin assay: Cycle 1, Day 1 (at the end of the infusion, 0.5 to 6 hours and 24 to 120 hours after eribulin infusion) and on Cycle 1, Day 8 (pre-dose of eribulin and at the end of the infusion) ]
  Tmax is the time to the highest concentration of drug in the blood that is measured after a dose.
• Phase 1: Mean value of area under the concentration-time curve (AUC) [ Time Frame: Irinotecan (its metabolite) and eribulin: Cycle 1, Day 1 at the end of irinotecan and eribulin infusion, then at 1, 2, 4, 6, and 24 hours post eribulin infusion. Eribulin alone: 48, 72, 96, and 120 hours post eribulin infusion. ]
  AUC represents the overall amount of drug in the bloodstream after dosing.
• Phase 2: Mean value of AUC [ Time Frame: Eribulin assay: Cycle 1, Day 1 (at the end of the infusion, 0.5 to 6 hours and 24 to 120 hours after eribulin infusion) and on Cycle 1, Day 8 (pre-dose of eribulin and at the end of the infusion) ]
  AUC represents the overall amount of drug in the bloodstream after dosing.
• Phase 2: Progression-free survival (PFS) [ Time Frame: Up to 36 months ]
  PFS is defined as the time from the first dose date to the date of disease progression as determined by investigator review, or death.
• Phase 2: The Clinical Benefit Rate (CBR) at week 12 [ Time Frame: Week 12 ]
  CBR is defined as the percentage of participants with a best overall response (BOR) of CR, PR or durable stable disease (SD) based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (durable SD >11 weeks).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study Evaluating the Safety and Efficacy of Eribulin Mesilate in Combination With Irinotecan Hydrochloride in Children With Refractory or Recurrent Solid Tumors
• Official Title: A Phase 1/2 Single-arm Study Evaluating the Safety and Efficacy of Eribulin Mesilate in Combination With Irinotecan in Children With Refractory or Recurrent Solid Tumors

Brief Summary

The Phase 1 part of the study is conducted to determine the maximum tolerated dose (MTD) and Recommended Phase 2 Dose (RP2D) of eribulin mesilate in combination with irinotecan hydrochloride in pediatric participants with relapsed/refractory solid tumors (excluding central nervous system [CNS] tumors).

The Phase 2 part of the study is conducted to assess the objective response rate (ORR) and duration of response (DOR) of eribulin mesilate in combination with irinotecan hydrochloride in pediatric participants with relapsed/refractory rhabdomyosarcoma (RMS), non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) and ewing sarcoma (EWS).

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Refractory or Recurrent Solid Tumors
• Rhabdomyosarcoma
• Non-Rhabdomyosarcoma Soft Tissue Sarcoma
• Ewing Sarcoma

Intervention

• Drug: Eribulin mesilate
  IV infusion
  Other Name: E7389
• Drug: Irinotecan hydrochloride
  IV infusion
  Other Name: (S)-4,11-diethyl-39 3,4,12,14-tetrahydro-4-hydroxy-3,14-dioxo-1H-pyrano[3',4':6,7]-indolizino[1,2-b]quinolin-9-4-yl-[1,4'-bipiperidine]-1'-carboxylate, monohydrochloride, trihydrate

Study Arms

Experimental: Eribulin mesilate plus irinotecan hydrochloride

In Schedules A and B, eribulin mesilate at the dose of 1.4 milligrams per meters squared (mg/m^2) will be administered as an intravenous (IV) infusion on Days 1 and 8 of each 21-day cycle. In Schedule A, irinotecan hydrochloride at the doses of 20 mg/m^2 or 40 mg/m^2 will be administered as an IV infusion on Days 1 to 5 of a 21-day cycle. In Schedule B, irinotecan hydrochloride at the doses of 100 mg/m^2 or 125 mg/m^2 will be administered as an IV infusion on Days 1 and 8 of a 21-day cycle.

Interventions:

• Drug: Eribulin mesilate
• Drug: Irinotecan hydrochloride

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 26, 2021): 40
• Original Estimated Enrollment (submitted: August 8, 2017): 86
• Actual Study Completion Date: May 17, 2021
• Actual Primary Completion Date: May 17, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Participants must be

• >=12 months to less than or equal to (<=) 25 years old at the time of consent [no more than 25 percent (%) of participants between the ages of 18 and 25 years will be enrolled in this study].
• In Phase 1, >6 months and <12 months at the time of consent (Schedule A only) participants will be enrolled one dose level behind the >=12 months participant in order to maximize safety for infant participants. In Phase 2, participants aged >6 months and <12 months at the time of consent will be enrolled to Schedule A with a modified dose of eribulin with the irinotecan dose maintained in order to maximize safety for infant participants.

Inclusion Criteria:

• Phase 1: Participants must be diagnosed with histologically confirmed solid tumors (excluding CNS tumors), which is relapsed or refractory, and for which there are no currently available therapies.
• Phase 2: Participants must be diagnosed with histologically confirmed RMS, NRSTS or EWS which is relapsed or refractory having received at least 1 prior therapy, including primary treatment.
• Phase 1: Participants must have either measurable or evaluable disease as per RECIST 1.1.
• Phase 2: Participants must have measurable disease as per RECIST 1.1.
• Participant's current disease state must be one for which there is no known curative therapy.
• Participant's performance score must be >=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 the performance score.

• Participants must have fully recovered from the acute toxic effects of all prior anticancer treatments prior to study drug administration:

  • Must not have received myelosuppressive chemotherapy within 21 days prior to study drug administration (42 days if prior nitrosourea).
  • Must not have received a long-acting growth factor (example, Neulasta) within 14 days or a short-acting growth factor within 7 days.
  • Must not have received an antineoplastic targeted therapy within 14 days.
  • Must not have received immunotherapy, example, tumor vaccines, within 42 days.
  • Must not have received monoclonal antibodies within at least 3 half-lives of the antibody after its last dose.
  • Must not have received radiotherapy (XRT) within 14 days prior to study drug administration (small field) or 42 days for craniospinal XRT, or if >=50% radiation of pelvis.
  • At least 84 days must have elapsed after stem cell infusion prior to study drug administration
  • No evidence of active graft-versus-host disease (GVHD) and at least 100 days must have elapsed after allogeneic bone marrow transplant or stem cell infusion prior to study drug administration

• Participants must have adequate bone marrow function, defined as:

  • Peripheral absolute neutrophil count (ANC) >=1.0*10^9/liter (L).
  • Platelet count >=100*10^9/L (not receiving platelet transfusions within a 7-day period prior to study drug administration).
  • Hemoglobin (Hb) at least 8.0 grams per deciliter (g/dL) at baseline (blood transfusions are allowed during the screening period to correct Hb values <8.0 g/dL).

• Participants must have adequate renal function, defined as:

  • A serum creatinine based on age/gender, derived from the Schwartz formula for estimating glomerular filtration rate (GFR), per protocol-specified criteria.
  • Serum creatinine clearance or GFR >=50 milliliters/minute/1.73 m^2, based on a 12 or 24 hours (h) urine creatinine collection.

• Participants must have adequate liver function, defined as:

  • Bilirubin (sum of conjugated + unconjugated) <=1.5 times the upper limit of normal (ULN) for age.
  • Alkaline phosphatase, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=3*ULN (in the case of liver metastases <=5*ULN), unless there are bone metastases, in which case liver-specific alkaline phosphatase must be separated from the total and used to assess the liver function instead of the total alkaline phosphatase.
  • Serum albumin >=2 g/dL.
• All participants and/or their parents or guardians must sign a written informed consent.
• Participants must be willing to comply with all aspects of the protocol.

Exclusion Criteria:

• Females who are breastfeeding or pregnant at Screening or Baseline. A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 h before the first dose of study drug.

• Females of childbearing potential 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, that is:
  • Total abstinence (if it is their preferred and usual lifestyle)
  • An intrauterine device (IUD) or intrauterine system (IUS)
  • A contraceptive implant
  • An oral contraceptive OR
  • Do not have a vasectomized partner with confirmed azoospermia.
• Males who have not had a successful vasectomy (confirmed azoospermia) or they and their female partners do not meet the criteria above (that is, 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.

• Concomitant Medications:

  • Participants receiving corticosteroids who have not been on a stable dose for at least 7 days prior to study drug administration.
  • Participants who are currently receiving other anticancer agents.
  • Participants who are receiving cyclosporine, tacrolimus or other agents to prevent GVHD post bone marrow transplant.
  • Participants who are receiving strong cytochrome P450 3A4 (CYP3A4) inhibitors and inducers including traditional herbal medicinal products (example, St. John's Wort).
• Phase 1: Received prior therapy with eribulin mesilate within 6 months prior to study drug administration.
• Phase 2: Received prior therapies with eribulin mesilate or irinotecan hydrochloride (for prior irinotecan hydrochloride, participants can be included if there was no tumor progression during irinotecan therapy).
• Any other malignancy that required treatment (except non-melanoma skin cancer, or histologically confirmed complete excision of carcinoma in situ), within 2 years prior to study drug administration.
• Has hypersensitivity to either study drug or any of the excipients.
• Has a known prior history of viral hepatitis (B or C) as demonstrated by positive serology (presence of antigens) or have an uncontrolled infection requiring treatment
• Has >Grade 1 peripheral sensory neuropathy or >Grade 1 peripheral motor neuropathy graded according to the Modified ("Balis") Pediatric Scale of Peripheral Neuropathies.

• Has cardiac pathology, defined as:

  • Participants with known congestive heart failure, symptomatic or Left ventricular (LV) ejection fraction <50% or shortening fraction <27% and participants with congenital long QT syndrome, bradyarrhythmias, or QT interval (QTc)>480 milliseconds on at least 2 separate electrocardiograms (ECGs).
• Has CNS disease: Participants with brain or subdural metastases are not eligible unless the metastases are asymptomatic and do not require treatment or have been adequately treated by local therapy and have discontinued the use of corticosteroids for this indication for at least 28 days prior to study drug administration. Participants must be clinically stable. It is not the intention of this protocol to treat participants with active brain metastases.

Note: Screening CNS imaging for participants with a known history of CNS disease is required.

• Have had or are planning to have the following invasive procedures:

  • Major surgical procedure or significant traumatic injury within 28 days prior to study drug administration.
  • Laparoscopic procedure or open biopsy within 7 days prior to study drug administration
  • Central line placement or subcutaneous port placement is not considered major surgery.
  • Core biopsy, including bone marrow biopsy within 2 days prior to study drug administration.
  • Fine needle aspirate within 3 days prior to study drug administration.
• Participants with known human immunodeficiency virus (HIV); due to lack of available safety data for eribulin therapy in HIV infected participants.
• Has any serious concomitant illness that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments (including active or severe chronic inflammatory bowel disease or bowel obstruction).
• Has received a live-virus vaccination within 30 days of planned start of study therapy. Seasonal flu vaccines that do not contain live virus are permitted.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Months to 25 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Germany, Greece, Italy, Poland, Spain, Switzerland, United Kingdom

Administrative Information

• NCT Number: NCT03245450
• Other Study ID Numbers: E7389-G000-213; 2016-003352-67 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Eisai Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Eisai Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Eisai Inc.
• Verification Date: June 2021