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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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:
Information provided by (Responsible Party):
Eisai Inc.

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Refractory or Recurrent Solid Tumors
Rhabdomyosarcoma
Non-Rhabdomyosarcoma Soft Tissue Sarcoma
Ewing Sarcoma
Interventions Drug: Eribulin mesilate
Drug: Irinotecan hydrochloride
Enrollment 40
Recruitment Details Participants took part in the study at 22 investigative sites in France, Germany, Greece, Italy, Poland, Spain and United Kingdom from 05 March 2018 to 17 May 2021.
Pre-assignment Details A total of 46 participants were screened, out of which 13 participants were treated in the Phase 1 and 27 participants were treated in Phase 2 (9 participants each in the relapsed/refractory rhabdomyosarcoma [RMS], non-rhabdomyosarcoma soft tissue sarcoma [NRSTS], and Ewing sarcoma [EWS] cohorts).
Arm/Group Title Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2 Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2 Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2 Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2
Hide Arm/Group Description Participants received eribulin mesilate 1.4 mg/m^2 (milligram per square meter) intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent. Participants received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent. Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 100 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent. Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 125 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent. Participants with RMS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent. Participants with NRSTS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent. Participants with EWS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.
Period Title: Overall Study
Started 3 4 3 3 9 9 9
Completed 0 0 0 0 0 0 0
Not Completed 3 4 3 3 9 9 9
Reason Not Completed
Radiological disease progression             3             3             2             2             7             6             6
Clinical disease progression             0             0             1             0             0             2             0
Other             0             0             0             1             1             1             1
Withdrawal by Subject             0             1             0             0             0             0             0
Adverse Event             0             0             0             0             1             0             2
Arm/Group Title Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2 Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2 Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2 Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Total
Hide Arm/Group Description Participants received eribulin mesilate 1.4 mg/m^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent. Participants received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent. Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 100 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent. Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 125 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent. Participants with RMS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent. Participants with NRSTS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent. Participants with EWS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent. Total of all reporting groups
Overall Number of Baseline Participants 3 4 3 3 9 9 9 40
Hide Baseline Analysis Population Description
Full analysis set included all participants who received at least 1 dose of either study drug.
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Phase 1 Number Analyzed 3 participants 4 participants 3 participants 3 participants 0 participants 0 participants 0 participants 13 participants
10.94  (6.583) 7.33  (2.540) 13.97  (4.231) 8.06  (4.997) 9.87  (4.842)
Phase 2 Number Analyzed 0 participants 0 participants 0 participants 0 participants 9 participants 9 participants 9 participants 27 participants
11.05  (3.845) 12.71  (4.348) 11.59  (3.753) 11.78  (3.899)
[1]
Measure Analysis Population Description: Per the planned analysis, baseline data for participants in Phase 1 and Phase 2 were not combined, therefore Mean and Standard Deviation are presented separately for Phase 1 and Phase 2 participants.
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 4 participants 3 participants 3 participants 9 participants 9 participants 9 participants 40 participants
Children (2-11 years)
1
  33.3%
4
 100.0%
1
  33.3%
2
  66.7%
5
  55.6%
3
  33.3%
4
  44.4%
20
  50.0%
Adolescents (12-17 years)
2
  66.7%
0
   0.0%
2
  66.7%
1
  33.3%
4
  44.4%
6
  66.7%
5
  55.6%
20
  50.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 4 participants 3 participants 3 participants 9 participants 9 participants 9 participants 40 participants
Female
2
  66.7%
1
  25.0%
2
  66.7%
2
  66.7%
5
  55.6%
2
  22.2%
5
  55.6%
19
  47.5%
Male
1
  33.3%
3
  75.0%
1
  33.3%
1
  33.3%
4
  44.4%
7
  77.8%
4
  44.4%
21
  52.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 4 participants 3 participants 3 participants 9 participants 9 participants 9 participants 40 participants
Hispanic or Latino
0
   0.0%
1
  25.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
2
   5.0%
Not Hispanic or Latino
3
 100.0%
3
  75.0%
3
 100.0%
3
 100.0%
9
 100.0%
8
  88.9%
9
 100.0%
38
  95.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 4 participants 3 participants 3 participants 9 participants 9 participants 9 participants 40 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   2.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
1
   2.5%
White
3
 100.0%
4
 100.0%
2
  66.7%
3
 100.0%
5
  55.6%
8
  88.9%
8
  88.9%
33
  82.5%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
4
  44.4%
0
   0.0%
1
  11.1%
5
  12.5%
1.Primary Outcome
Title Phase 1: Recommended Phase 2 Dose (RP2D) of Eribulin Mesilate in Combination With Irinotecan Hydrochloride
Hide Description 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.
Time Frame First dose of study drug up to Cycle 1 (Cycle length=21 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The Dose Evaluable Set (DES) for Phase 1 included all the participants who completed Cycle 1 treatment and were evaluated for DLTs and those who discontinued treatment during Cycle 1 due to DLTs.
Arm/Group Title Phase 1: All Participants
Hide Arm/Group Description:
All participants received eribulin mesilate 1.4 mg/m^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m^2 or 40 mg/m^2 intravenous infusion on Days 1 to 5 (schedule A) and irinotecan hydrochloride 100 mg/m^2 or 125 mg/m^2 intravenous infusion on Days 1 and 8 (schedule B) in 21-day treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Overall Number of Participants Analyzed 12
Measure Type: Number
Unit of Measure: mg/m^2
Eribulin Mesilate 1.4
Irinotecan Hydrochloride 40
2.Primary Outcome
Title Phase 2: Objective Response Rate (ORR)
Hide Description 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.
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
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all participants who received at least 1 dose of either study drug.
Arm/Group Title Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2
Hide Arm/Group Description:
Participants with RMS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants with NRSTS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.
Participants with EWS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.
Overall Number of Participants Analyzed 9 9 9
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of participants
11.1
(0.6 to 42.9)
11.1
(0.6 to 42.9)
11.1
(0.6 to 42.9)
3.Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Hide Description 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.
Time Frame From first dose of study drug up to approximately 2 years 4 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least 1 dose of either study drug.
Arm/Group Title Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2 Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2 Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2 Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2
Hide Arm/Group Description:
Participants received eribulin mesilate 1.4 mg/m^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 100 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 125 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants with RMS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants with NRSTS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.
Participants with EWS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.
Overall Number of Participants Analyzed 3 4 3 3 9 9 9
Measure Type: Count of Participants
Unit of Measure: Participants
3
 100.0%
4
 100.0%
3
 100.0%
3
 100.0%
9
 100.0%
9
 100.0%
9
 100.0%
4.Secondary Outcome
Title Number of Participants With Serious Adverse Event (SAE)
Hide Description 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.
Time Frame Up to approximately 2 years and 4 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least 1 dose of either study drug.
Arm/Group Title Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2 Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2 Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2 Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2
Hide Arm/Group Description:
Participants received eribulin mesilate 1.4 mg/m^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 100 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 125 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants with RMS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants with NRSTS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.
Participants with EWS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.
Overall Number of Participants Analyzed 3 4 3 3 9 9 9
Measure Type: Count of Participants
Unit of Measure: Participants
1
  33.3%
3
  75.0%
0
   0.0%
1
  33.3%
5
  55.6%
4
  44.4%
3
  33.3%
5.Secondary Outcome
Title Phase 1, Cmax: Maximum Observed Plasma Concentration of Eribulin, Irinotecan and Its Active Metabolite SN-38
Hide Description [Not Specified]
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)
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set included participants who had documented dosing history and at least one post-dosing quantifiable drug concentration.
Arm/Group Title Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2 Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2 Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2
Hide Arm/Group Description:
Participants received eribulin mesilate 1.4 mg/m^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 100 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 125 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Overall Number of Participants Analyzed 3 4 3 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanogram/milliliter (ng/mL)
Eribulin
369.3
(58.0% to N/A)
179.4
(136.1% to N/A)
348.7
(25.0% to N/A)
323.3
(20.6% to N/A)
Irinotecan
538.8
(165.9% to N/A)
399.5
(19.1% to N/A)
1168.1
(39.8% to N/A)
1555.4
(39.5% to N/A)
Active Metabolite SN-38
6.518
(9.4% to N/A)
17.170
(39.7% to N/A)
25.409
(51.6% to N/A)
18.614
(74.3% to N/A)
6.Secondary Outcome
Title Phase 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Eribulin, Irinotecan and Its Active Metabolite SN-38
Hide Description [Not Specified]
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)
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set included participants who had documented dosing history and at least one post-dosing quantifiable drug concentration.
Arm/Group Title Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2 Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2 Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2
Hide Arm/Group Description:
Participants received eribulin mesilate 1.4 mg/m^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 100 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 125 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Overall Number of Participants Analyzed 3 4 3 3
Median (Full Range)
Unit of Measure: hours
Eribulin
0.080
(0.03 to 0.22)
0.135
(0.03 to 1)
0.080
(0 to 0.12)
0.050
(0.01 to 0.12)
Irinotecan
0.250
(0.07 to 0.42)
0.305
(0 to 24)
0.300
(0.03 to 0.33)
0.170
(0.13 to 0.25)
Active Metabolite SN-38
0.420
(0.25 to 1.03)
0.305
(0 to 24)
0.330
(0.3 to 0.53)
0.250
(0.13 to 0.55)
7.Secondary Outcome
Title Phase 1, T1/2: Half-life of Eribulin, Irinotecan and Its Active Metabolite SN-38
Hide Description 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.
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)
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Hide Analysis Population Description
PK analysis set included participants who had documented dosing history and at least one post-dosing quantifiable drug concentration. Here 'N' (overall number of participants analyzed) included all participants who were evaluable for this outcome measure and 'n' (number analyzed) included all participants who were evaluable for each category.
Arm/Group Title Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2 Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2 Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2
Hide Arm/Group Description:
Participants received eribulin mesilate 1.4 mg/m^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 100 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 125 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Overall Number of Participants Analyzed 3 3 3 2
Median (Full Range)
Unit of Measure: hours
Eribulin Number Analyzed 3 participants 3 participants 3 participants 2 participants
27.50
(26.5 to 27.7)
34.70
(32.9 to 40.4)
30.00
(23.4 to 43.3)
25.30
(22.1 to 28.5)
Irinotecan Number Analyzed 0 participants 0 participants 3 participants 2 participants
5.140
(5.1 to 9.61)
4.430
(3.95 to 5.08)
Metabolite SN-38 Number Analyzed 0 participants 0 participants 3 participants 2 participants
12.000
(9.9 to 13.9)
10.390
(9.68 to 11.1)
8.Secondary Outcome
Title Phase 1, Total Clearance (CL) of Eribulin and Irinotecan
Hide Description 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.
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)
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set included participants who had documented dosing history and at least one post-dosing quantifiable drug concentration. Here 'N' (overall number of participants analyzed) included all participants who were evaluable for this outcome measure and 'n' (number analyzed) included all participants who were evaluable for each category.
Arm/Group Title Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2 Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2 Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2
Hide Arm/Group Description:
Participants received eribulin mesilate 1.4 mg/m^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 100 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 125 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Overall Number of Participants Analyzed 3 3 3 2
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: liter per hour (L/h)
Eribulin Number Analyzed 3 participants 3 participants 3 participants 2 participants
3.1781
(43.9%)
2.4581
(8.0%)
2.9060
(32.8%)
1.7521
(136.6%)
Irinotecan Number Analyzed 0 participants 0 participants 3 participants 2 participants
27.27
(23.2%)
30.30
(60.7%)
9.Secondary Outcome
Title Phase 1, Volume of Distribution (Vz) of Eribulin and Irinotecan
Hide Description 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.
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)
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set included participants who had documented dosing history and at least one post-dosing quantifiable drug concentration. Here 'N' (overall number of participants analyzed) included all participants who were evaluable for this outcome measure and 'n' (number analyzed) included all participants who were evaluable for each category.
Arm/Group Title Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2 Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2 Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2
Hide Arm/Group Description:
Participants received eribulin mesilate 1.4 mg/m^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 100 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 125 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Overall Number of Participants Analyzed 3 3 3 2
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: liter
Eribulin Number Analyzed 3 participants 3 participants 3 participants 2 participants
124.70
(41.5%)
126.96
(18.1%)
130.78
(35.9%)
63.35
(101.8%)
Irinotecan Number Analyzed 0 participants 0 participants 3 participants 2 participants
248.5
(16.1%)
195.1
(69.0%)
10.Secondary Outcome
Title 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
Hide Description [Not Specified]
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)
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set included participants who had documented dosing history and at least one post-dosing quantifiable drug concentration.
Arm/Group Title Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2 Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2 Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2
Hide Arm/Group Description:
Participants received eribulin mesilate 1.4 mg/m^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 100 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 125 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Overall Number of Participants Analyzed 3 4 3 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour*nanogram per milliliter (h*ng/mL)
Eribulin
422.5
(40.0% to N/A)
403.7
(32.1% to N/A)
616.9
(66.1% to N/A)
603.5
(87.3% to N/A)
Irinotecan
1812.6
(13.5% to N/A)
3686.1
(36.4% to N/A)
4693.9
(66.1% to N/A)
3633.7
(38.9% to N/A)
Metabolite SN-38
68.00
(19.7% to N/A)
145.04
(11.6% to N/A)
138.22
(42.2% to N/A)
65.47
(153.2% to N/A)
11.Secondary Outcome
Title 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
Hide Description 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.
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)
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set included participants who had documented dosing history and at least one post-dosing quantifiable drug concentration. Here 'N' (overall number of participants analyzed) included all participants who were evaluable for this outcome measure and 'n' (number analyzed) included all participants who were evaluable for each category.
Arm/Group Title Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2 Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2 Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2
Hide Arm/Group Description:
Participants received eribulin mesilate 1.4 mg/m^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 100 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 125 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Overall Number of Participants Analyzed 3 3 3 2
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
Eribulin Number Analyzed 3 participants 3 participants 3 participants 2 participants
438.1
(39.0%)
506.0
(16.6%)
666.9
(69.0%)
576.9
(133.6%)
Irinotecan Number Analyzed 0 participants 0 participants 3 participants 2 participants
5036.1
(70.9%)
3698.5
(39.2%)
Metabolite SN-38 Number Analyzed 0 participants 0 participants 3 participants 2 participants
169.0
(51.4%)
149.4
(4.3%)
12.Secondary Outcome
Title Phase 2: Progression Free Survival (PFS)
Hide Description 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.
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
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Hide Analysis Population Description
Full analysis set included all participants who received at least 1 dose of either study drug.
Arm/Group Title Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2
Hide Arm/Group Description:
Participants with RMS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants with NRSTS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.
Participants with EWS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.
Overall Number of Participants Analyzed 9 9 9
Median (90% Confidence Interval)
Unit of Measure: months
2.69
(1.28 to 8.87)
1.35
(1.15 to 2.79)
6.70
(1.38 to 8.84)
13.Secondary Outcome
Title Phase 2: Clinical Benefit Rate (CBR)
Hide Description 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.
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
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all participants who received at least 1 dose of either study drug.
Arm/Group Title Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2
Hide Arm/Group Description:
Participants with RMS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.
Participants with NRSTS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.
Participants with EWS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.
Overall Number of Participants Analyzed 5 3 5
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of participants
55.6
(25.1 to 83.1)
33.3
(9.8 to 65.5)
55.6
(25.1 to 83.1)
14.Secondary Outcome
Title Model Predicted Apparent Total Body Clearance (CL) of Eribulin
Hide Description 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.
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)
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set included all participants who had documented dosing history had at least one postdosing quantifiable drug concentration. Analysis population for this outcome measure included participants from current study E7389-G000-213 and from studies (NCT00069264,NCT00069277,NCT00326950,NCT00706095,NCT01000376,NCT01106248,NCT02171260, NCT00413192,NCT01458249,NCT03441360,NCT01327885)."Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.
Arm/Group Title Eribulin Mesilate - All Participants
Hide Arm/Group Description:
All participants who received eribulin mesilate intravenous infusion over the dose range 0.25 to 4.0 mg/m^2 in current study (E7389-G000-213) and studies (NCT00069264, NCT00069277, NCT00326950, NCT00706095, NCT01000376, NCT01106248, NCT02171260, NCT00413192, NCT01458249, NCT03441360 and NCT01327885).
Overall Number of Participants Analyzed 561
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: L/hr
2.89
(2.75 to 3.03)
15.Secondary Outcome
Title Volume of Distribution Estimates From the Population PK Model for Eribulin
Hide Description 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.
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)
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set included all participants who had documented dosing history had at least one postdosing quantifiable drug concentration. Analysis population for this outcome measure included participants from current study E7389-G000-213 and from studies (NCT00069264,NCT00069277,NCT00326950,NCT00706095,NCT01000376,NCT01106248,NCT02171260, NCT00413192,NCT01458249,NCT03441360,NCT01327885)."Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.
Arm/Group Title Eribulin Mesilate - All Participants
Hide Arm/Group Description:
All participants who received eribulin mesilate intravenous infusion over the dose range 0.25 to 4.0 mg/m^2 in current study (E7389-G000-213) and in studies (NCT00069264, NCT00069277, NCT00326950, NCT00706095, NCT01000376, NCT01106248, NCT02171260, NCT00413192, NCT01458249, NCT03441360 and NCT01327885).
Overall Number of Participants Analyzed 561
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: liter
V1
4.08
(3.87 to 4.29)
V2
2.03
(1.79 to 2.27)
V3
106
(101 to 111)
Time Frame From first dose of study drug up to approximately 2 year 4 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2 Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2 Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2 Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2
Hide Arm/Group Description Participants received eribulin mesilate 1.4 mg/m^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent. Participants received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent. Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 100 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent. Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 125 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent. Participants with RMS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent. Participants with NRSTS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent. Participants with EWS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.
All-Cause Mortality
Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2 Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2 Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2 Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/3 (33.33%)      2/4 (50.00%)      1/3 (33.33%)      1/3 (33.33%)      4/9 (44.44%)      3/9 (33.33%)      3/9 (33.33%)    
Hide Serious Adverse Events
Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2 Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2 Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2 Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/3 (33.33%)      3/4 (75.00%)      0/3 (0.00%)      1/3 (33.33%)      5/9 (55.56%)      4/9 (44.44%)      3/9 (33.33%)    
Blood and lymphatic system disorders               
Febrile neutropenia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 1/9 (11.11%)  1
Gastrointestinal disorders               
Abdominal pain † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
General disorders               
Pyrexia † 1  1/3 (33.33%)  1 2/4 (50.00%)  2 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Infections and infestations               
Bacteraemia † 1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0
Device related infection † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Sepsis † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1
Upper respiratory tract infection † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Metabolism and nutrition disorders               
Malnutrition † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0
Musculoskeletal and connective tissue disorders               
Pain in jaw † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Malignant neoplasm progression † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/3 (0.00%)  0 1/3 (33.33%)  1 1/9 (11.11%)  2 2/9 (22.22%)  2 0/9 (0.00%)  0
Malignant pleural effusion † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  2 1/9 (11.11%)  1 0/9 (0.00%)  0
Respiratory, thoracic and mediastinal disorders               
Dyspnoea † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
1
Term from vocabulary, MedDRA 24.0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2 Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2 Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2 Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2 Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/3 (100.00%)      4/4 (100.00%)      3/3 (100.00%)      3/3 (100.00%)      9/9 (100.00%)      9/9 (100.00%)      9/9 (100.00%)    
Blood and lymphatic system disorders               
Anaemia † 1  2/3 (66.67%)  3 2/4 (50.00%)  14 1/3 (33.33%)  6 1/3 (33.33%)  1 3/9 (33.33%)  9 4/9 (44.44%)  8 5/9 (55.56%)  29
Leukopenia † 1  1/3 (33.33%)  4 1/4 (25.00%)  14 2/3 (66.67%)  15 1/3 (33.33%)  12 0/9 (0.00%)  0 1/9 (11.11%)  1 3/9 (33.33%)  32
Lymphopenia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  3 0/9 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0
Neutropenia † 1  3/3 (100.00%)  39 2/4 (50.00%)  8 3/3 (100.00%)  18 1/3 (33.33%)  12 3/9 (33.33%)  15 2/9 (22.22%)  10 4/9 (44.44%)  52
Thrombocytopenia † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 1/3 (33.33%)  3 1/3 (33.33%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 5/9 (55.56%)  17
Leukocytosis † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Cardiac disorders               
Tachycardia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 2/9 (22.22%)  2 0/9 (0.00%)  0
Ear and labyrinth disorders               
Ear pain † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1
Gastrointestinal disorders               
Abdominal pain † 1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 7/9 (77.78%)  9 2/9 (22.22%)  3 2/9 (22.22%)  2
Abdominal pain upper † 1  1/3 (33.33%)  1 0/4 (0.00%)  0 2/3 (66.67%)  2 0/3 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0
Constipation † 1  2/3 (66.67%)  3 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/9 (22.22%)  2 0/9 (0.00%)  0 2/9 (22.22%)  2
Diarrhoea † 1  1/3 (33.33%)  1 1/4 (25.00%)  12 0/3 (0.00%)  0 0/3 (0.00%)  0 4/9 (44.44%)  24 5/9 (55.56%)  11 5/9 (55.56%)  9
Nausea † 1  1/3 (33.33%)  2 1/4 (25.00%)  1 2/3 (66.67%)  2 0/3 (0.00%)  0 4/9 (44.44%)  5 6/9 (66.67%)  8 1/9 (11.11%)  1
Oral pain † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0
Toothache † 1  1/3 (33.33%)  2 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Vomiting † 1  0/3 (0.00%)  0 2/4 (50.00%)  2 3/3 (100.00%)  10 1/3 (33.33%)  3 6/9 (66.67%)  8 2/9 (22.22%)  2 1/9 (11.11%)  4
Abdominal distension † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  2 0/9 (0.00%)  0 0/9 (0.00%)  0
Anal fissure † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0
Anal inflammation † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1
Aphthous ulcer † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0
Gingival pain † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 1/9 (11.11%)  1 0/9 (0.00%)  0
Haematemesis † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Haematochezia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1
Hypoaesthesia oral † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  4 0/9 (0.00%)  0 0/9 (0.00%)  0
Mouth ulceration † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  4 1/9 (11.11%)  1 0/9 (0.00%)  0
Odynophagia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1
Proctalgia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0
Stomatitis † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/9 (22.22%)  5 0/9 (0.00%)  0 1/9 (11.11%)  4
Tongue ulceration † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0
General disorders               
Asthenia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 2/9 (22.22%)  2 3/9 (33.33%)  3 0/9 (0.00%)  0
Catheter site pain † 1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0
Non-cardiac chest pain † 1  1/3 (33.33%)  1 0/4 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  2
Pyrexia † 1  1/3 (33.33%)  1 0/4 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 1/9 (11.11%)  1 2/9 (22.22%)  3 5/9 (55.56%)  8
Catheter site pruritus † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Fatigue † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/9 (22.22%)  5 3/9 (33.33%)  3 2/9 (22.22%)  4
Gait disturbance † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1
Oedema peripheral † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 1/9 (11.11%)  1
Pain † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 1/9 (11.11%)  2 1/9 (11.11%)  1
Infections and infestations               
Conjunctivitis † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0
Rhinitis † 1  1/3 (33.33%)  1 0/4 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 3/9 (33.33%)  3 0/9 (0.00%)  0 1/9 (11.11%)  2
Tonsillitis † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0
Vascular device infection † 1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0
Bacterial infection † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
COVID-19 † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0
Device related infection † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Ear infection † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1
Herpes simplex † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Influenza † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0
Nasopharyngitis † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0
Oral candidiasis † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 1/9 (11.11%)  1
Pneumonia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1
Respiratory tract infection † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1
Upper respiratory tract infection † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0
Urinary tract infection † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0
Injury, poisoning and procedural complications               
Procedural nausea † 1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Urostomy complication † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0
Contusion † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Fall † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1
Mouth injury † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Wound dehiscence † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  2 0/9 (0.00%)  0 0/9 (0.00%)  0
Investigations               
Alanine aminotransferase increased † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/3 (33.33%)  2 0/3 (0.00%)  0 1/9 (11.11%)  10 1/9 (11.11%)  2 2/9 (22.22%)  9
Aspartate aminotransferase increased † 1  0/3 (0.00%)  0 1/4 (25.00%)  2 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  4 0/9 (0.00%)  0 1/9 (11.11%)  5
C-reactive protein increased † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Lymphocyte count decreased † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/3 (0.00%)  0 1/3 (33.33%)  1 1/9 (11.11%)  8 0/9 (0.00%)  0 2/9 (22.22%)  5
Neutrophil count decreased † 1  0/3 (0.00%)  0 3/4 (75.00%)  8 0/3 (0.00%)  0 2/3 (66.67%)  7 6/9 (66.67%)  21 3/9 (33.33%)  22 5/9 (55.56%)  46
Weight decreased † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 1/3 (33.33%)  1 0/3 (0.00%)  0 2/9 (22.22%)  2 0/9 (0.00%)  0 1/9 (11.11%)  1
White blood cell count decreased † 1  0/3 (0.00%)  0 3/4 (75.00%)  7 0/3 (0.00%)  0 1/3 (33.33%)  1 1/9 (11.11%)  20 1/9 (11.11%)  6 0/9 (0.00%)  0
Blood albumin decreased † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0
Blood calcium decreased † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Blood creatinine increased † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1
Blood phosphorus decreased † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Blood potassium decreased † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Blood sodium decreased † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  2 0/9 (0.00%)  0
Blood urea increased † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Electrocardiogram QT prolonged † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  2 1/9 (11.11%)  2
Gamma-glutamyltransferase increased † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1
Haematocrit decreased † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  7 0/9 (0.00%)  0 0/9 (0.00%)  0
Metamyelocyte count increased † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Myelocyte count increased † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Red blood cell count decreased † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  5 0/9 (0.00%)  0 0/9 (0.00%)  0
Metabolism and nutrition disorders               
Decreased appetite † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 4/9 (44.44%)  5 3/9 (33.33%)  3 0/9 (0.00%)  0
Hypophosphataemia † 1  1/3 (33.33%)  1 0/4 (0.00%)  0 1/3 (33.33%)  2 0/3 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  3
Vitamin D deficiency † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0
Hypokalaemia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/9 (22.22%)  7 0/9 (0.00%)  0 2/9 (22.22%)  10
Hypomagnesaemia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  2 1/9 (11.11%)  1 0/9 (0.00%)  0
Refeeding syndrome † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0
Musculoskeletal and connective tissue disorders               
Back pain † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 1/9 (11.11%)  1 2/9 (22.22%)  4 0/9 (0.00%)  0
Bone pain † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 3/9 (33.33%)  3
Muscle spasms † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 2/9 (22.22%)  2 0/9 (0.00%)  0 0/9 (0.00%)  0
Musculoskeletal chest pain † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 2/9 (22.22%)  2
Spinal pain † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Arthralgia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  2 2/9 (22.22%)  5 2/9 (22.22%)  5
Groin pain † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  2 0/9 (0.00%)  0
Neck pain † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1
Pain in extremity † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 2/9 (22.22%)  3 1/9 (11.11%)  4
Pain in jaw † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  4 0/9 (0.00%)  0 1/9 (11.11%)  3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Cancer pain † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Tumour pain † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Nervous system disorders               
Headache † 1  1/3 (33.33%)  1 0/4 (0.00%)  0 1/3 (33.33%)  1 1/3 (33.33%)  1 4/9 (44.44%)  6 0/9 (0.00%)  0 1/9 (11.11%)  2
Paraesthesia † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0
Neuralgia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1
Peripheral sensorimotor neuropathy † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 1/9 (11.11%)  3
Peripheral sensory neuropathy † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  4 1/9 (11.11%)  1
Syncope † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Psychiatric disorders               
Insomnia † 1  0/3 (0.00%)  0 1/4 (25.00%)  3 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 1/9 (11.11%)  1 1/9 (11.11%)  1
Agitation † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0
Anxiety † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Depressed mood † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  8 0/9 (0.00%)  0 0/9 (0.00%)  0
Negative thoughts † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Tearfulness † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  3 0/9 (0.00%)  0 0/9 (0.00%)  0
Renal and urinary disorders               
Acute kidney injury † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1
Haematuria † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 1/9 (11.11%)  1 1/9 (11.11%)  3
Urinary tract pain † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Respiratory, thoracic and mediastinal disorders               
Cough † 1  1/3 (33.33%)  1 0/4 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 2/9 (22.22%)  3 0/9 (0.00%)  0 1/9 (11.11%)  1
Hypoxia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0
Pleuritic pain † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1
Respiratory distress † 1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0
Allergic cough † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0
Dyspnoea † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Epistaxis † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/9 (22.22%)  2 1/9 (11.11%)  2 0/9 (0.00%)  0
Haemoptysis † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Laryngeal inflammation † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Oropharyngeal pain † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/9 (22.22%)  3 0/9 (0.00%)  0 0/9 (0.00%)  0
Pneumothorax † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 1/9 (11.11%)  1
Pulmonary embolism † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0
Rhinorrhoea † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Skin and subcutaneous tissue disorders               
Alopecia † 1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 2/9 (22.22%)  3 0/9 (0.00%)  0 0/9 (0.00%)  0
Dermatitis † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1
Dry skin † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0
Rash † 1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Skin oedema † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0
Leukonychia † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Palmar-plantar erythrodysaesthesia syndrome † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0
Papule † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0
Pruritus † 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 2/9 (22.22%)  2
1
Term from vocabulary, MedDRA 24.0
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Eisai Medical Information
Organization: Eisai Inc.
Phone: 1-888-274-2378
EMail: esi_oncmedinfo@eisai.com
Layout table for additonal information
Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT03245450    
Other Study ID Numbers: E7389-G000-213
2016-003352-67 ( EudraCT Number )
First Submitted: August 8, 2017
First Posted: August 10, 2017
Results First Submitted: May 16, 2022
Results First Posted: June 28, 2022
Last Update Posted: June 28, 2022