Back to resultsAn Open-label, Multicenter, Phase 2 Study to Evaluate the Efficacy and Safety of Eribulin Mesylate in Previously Treated Subjects With Advanced or Metastatic Soft Tissue Sarcoma (Study E7389-J081-217)
Primary Purpose
Soft Tissue Sarcoma
Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
eribulin mesylate
Sponsored by
About this trial
This is an interventional treatment trial for Soft Tissue Sarcoma focused on measuring Soft Tissue Sarcoma
Eligibility Criteria
Inclusion Criteria
- Histologically or cytologically confirmed soft tissue sarcoma of high or intermediate grade
- Documented evidence of advanced or metastatic soft tissue sarcoma, not amenable to surgery or radiotherapy
- Within 6 months from the radiographic evidence of disease progression by RECIST criteria in the last chemotherapy regimen for advanced or metastatic soft tissue sarcoma
- Presence of measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
- Subjects who received at least one standard chemotherapy for advanced soft tissue sarcoma (an anthracycline or an ifosfamide monotherapy, or a combination therapy)
- Subjects aged ≥ 20 years at the time of informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
- Adequate organ function
- Voluntary agreement to provide written informed consent
Exclusion Criteria
- A history of malignancies or recurrence within 5 years after the remission
- Significant cardiovascular impairment
- Any serious concomitant illness or infection requiring treatment.
- Hypersensitivity to either halichondrin B or halichondrin B chemical derivatives or both.
- Subjects who have previously participated in a study with eribulin (whether treated with eribulin or not).
- Any medical or other condition which, in the opinion of the principal investigator, will preclude participation in a clinical trial.
- Subjects who have received any anti-cancer therapy, including surgery, radiotherapy, immunotherapy, cytotoxic, hormonal, biological (including humanized antibodies) and targeted agents within 21 days, or any investigational agent within 30 days, prior to the first dose of study drug.
- Subjects who have not recovered from toxicities as a result of prior anti-cancer therapy to ≤ Grade 1, according to Common Terminology Criteria for Adverse Events (CTCAE), except for peripheral neuropathy of Grade 2 and alopecia.
- Subjects with known cerebral metastases with clinical symptoms or requiring treatment.
- Pre-existing peripheral neuropathy > CTCAE Grade 2.
- Female subjects must not be pregnant with a negative by the pregnancy test at Screening, or breastfeeding.
- Subjects participating in other clinical trials
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
eribulin mesylate 1.4 mg/m^2
Arm Description
Outcomes
Primary Outcome Measures
Progression-free Rate at 12 Weeks (PFR12wks)
The PFR at 12 weeks was the percentage of participants with progression-free survival (success) measured as a binary variable based on the tumor response assessed at Week 12 after the start of study treatment. Participants were considered a success if one radiological evaluation performed at least Week 12 after start of therapy indicated stable disease (SD), or complete response (CR) or partial response (PR), as defined according to Response Evaluation Criteria in Solid Tumor version 1.1 (RECIST v1.1); all other cases were considered as failures (including disease progression or death before the Week 12 evaluation, or had unknown disease status at Week 12). If new anticancer treatments were started before the Week 12 evaluation, participants were considered failures. A 2-sided 90% confidence interval (CI) was calculated using the exact method of binomial distribution.
Secondary Outcome Measures
Progression-Free Survival (PFS)
Progression-free survival was defined as the time from the date of treatment start to the first documented date of event (disease progression or death from any cause, whichever occurred first). PFS was assessed every six weeks (until disease progression was confirmed, or sooner, if clinically indicated) and was based on Investigator and Independent Review Committee (IRC) assessments according to RECIST v1.1. Disease progression was measured using computed tomography (CT) or magnetic resonance imaging (MRI) on targeted tumors and defined as at least a 20% relative increase and 5 mm absolute increase in the sum of diameters of target lesions (taking as reference the smallest sum on study), recorded since the treatment started or the appearance of 1 or more new lesions. A 95% CI was calculated using Kaplan-Meier estimate and Greenwood Formula. A generalized Brookmeyer and Crowley method was used to construct a log-log-transformed 95% CI.
Overall Survival (OS)
Overall survival was defined as the time from the date of treatment start to the date of death from any cause. Participants were followed for survival every twelve weeks after PD. In the absence of confirmation of death, participants were censored either at the date that the participant was last known alive or the date of study cutoff, whichever came earlier. Participants censored before database cutoff included those who were lost to follow up and who withdrew consent. A 95% CI was calculated using Kaplan-Meier estimate and Greenwood Formula. A generalized Brookmeyer and Crowley method is used to construct a log-log-transformed 95% CI.
Objective Response Rate (ORR)
Objective response rate was defined as the percentage of participants who had a best overall rate (BOR) of CR or PR. Tumor assessment was performed at Week 6 and Week 12 after the start of study treatment, and every six weeks thereafter. The BOR of CR and PR in this study required confirmation by a subsequent assessment of response at least four weeks (28 days) later. CR and PR were determined by the Investigator and IRC using RECIST v1.1 for target lesions assessed by MRI/CT scans. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. A 95% CI was calculated using exact method of binomial distribution.
Disease Control Rate (DCR)
Disease control rate was defined as the percentage of participants who had BOR of CR + PR + SD. BOR of SD must have manifested at least five weeks (35 days) after the first dose of study treatment. Tumor assessment was performed at Week 6 and Week 12 after the start of treatment, and every six weeks thereafter. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of the longest diameter since the treatment started. A 95% CI was calculated using exact method of binomial distribution.
Clinical Benefit Rate (CBR)
CBR was defined as the percentage of participants who had a BOR of CR + PR + dSD (duration of SD greater than or equal to 11 weeks [77 days] after the first dose of study treatment). Tumor assessment was performed at Week 6 and Week 12 after the start of study treatment, and every six weeks thereafter. For participants whose BOR was SD, the duration of SD was defined as the time from the date of the first dose of study treatment to the first documented PD or death, whichever occurred first (i.e., same definition of PFS). If the dSD was censored at a time less than 11 weeks, the participant was considered as not having a clinical benefit. A 95% CI was calculated using exact method of binomial distribution.
Durable Stable Disease (SD) Rate (dSDR)
Durable stable disease rate was defined as the percentage of participants who manifested durable stable disease (the duration of stable disease for greater than or equal to eleven weeks) and was estimated based on the tumor response assessments performed according to RECIST v1.1. Tumor assessment was performed at Week 6 and Week 12 after the start of study treatment, and every six weeks thereafter. A 2-sided 95% CI was calculated using the exact method of binomial distribution.
Best Overall Response (BOR)
The best overall response categories (CR, PR, SD [including non-CR/non-PD], PD, not evaluable [NE], and unknown [UNK]) were derived based on time point tumor responses during the study as assessed by the IRC as well as the investigator. Tumor assessment was performed at Week 6 and Week 12 after the start of study treatment, and every six weeks thereafter. BOR of SD must have occurred at least 35 days (at least 5 weeks) after the first dose of study drug. If a participant had a BOR of non-CR/non-PD, the participant's BOR was grouped with the SD category.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01458249
Brief Title
An Open-label, Multicenter, Phase 2 Study to Evaluate the Efficacy and Safety of Eribulin Mesylate in Previously Treated Subjects With Advanced or Metastatic Soft Tissue Sarcoma (Study E7389-J081-217)
Official Title
An Open-label, Multicenter, Phase 2 Study to Evaluate the Efficacy and Safety of Eribulin Mesylate in Previously Treated Subjects With Advanced or Metastatic Soft Tissue Sarcoma
Study Type
Interventional
2. Study Status
Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
November 2011 (undefined)
Primary Completion Date
November 2014 (Actual)
Study Completion Date
February 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eisai Co., Ltd.
4. Oversight
5. Study Description
Brief Summary
The purpose of the study is to evaluate the efficacy and safety of eribulin mesylate in subjects with soft tissue sarcoma who received at least one standard chemotherapy (an anthracycline or an ifosfamide monotherapy or a combination therapy).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Soft Tissue Sarcoma
Keywords
Soft Tissue Sarcoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
52 (Actual)
8. Arms, Groups, and Interventions
Arm Title
eribulin mesylate 1.4 mg/m^2
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
eribulin mesylate
Other Intervention Name(s)
E7389
Intervention Description
Administration of eribulin mesylate at a dose of 1.4 mg/m^2 as an IV bolus infusion over 2-5 minutes on Days 1 and 8 of every cycle, where the duration of each cycle is 21 days.
Primary Outcome Measure Information:
Title
Progression-free Rate at 12 Weeks (PFR12wks)
Description
The PFR at 12 weeks was the percentage of participants with progression-free survival (success) measured as a binary variable based on the tumor response assessed at Week 12 after the start of study treatment. Participants were considered a success if one radiological evaluation performed at least Week 12 after start of therapy indicated stable disease (SD), or complete response (CR) or partial response (PR), as defined according to Response Evaluation Criteria in Solid Tumor version 1.1 (RECIST v1.1); all other cases were considered as failures (including disease progression or death before the Week 12 evaluation, or had unknown disease status at Week 12). If new anticancer treatments were started before the Week 12 evaluation, participants were considered failures. A 2-sided 90% confidence interval (CI) was calculated using the exact method of binomial distribution.
Time Frame
Week 12
Secondary Outcome Measure Information:
Title
Progression-Free Survival (PFS)
Description
Progression-free survival was defined as the time from the date of treatment start to the first documented date of event (disease progression or death from any cause, whichever occurred first). PFS was assessed every six weeks (until disease progression was confirmed, or sooner, if clinically indicated) and was based on Investigator and Independent Review Committee (IRC) assessments according to RECIST v1.1. Disease progression was measured using computed tomography (CT) or magnetic resonance imaging (MRI) on targeted tumors and defined as at least a 20% relative increase and 5 mm absolute increase in the sum of diameters of target lesions (taking as reference the smallest sum on study), recorded since the treatment started or the appearance of 1 or more new lesions. A 95% CI was calculated using Kaplan-Meier estimate and Greenwood Formula. A generalized Brookmeyer and Crowley method was used to construct a log-log-transformed 95% CI.
Time Frame
Cycle 1 (Day 1) to progressive disease (PD) or death, or date of study cutoff (14 Nov 2014) up to 3 years
Title
Overall Survival (OS)
Description
Overall survival was defined as the time from the date of treatment start to the date of death from any cause. Participants were followed for survival every twelve weeks after PD. In the absence of confirmation of death, participants were censored either at the date that the participant was last known alive or the date of study cutoff, whichever came earlier. Participants censored before database cutoff included those who were lost to follow up and who withdrew consent. A 95% CI was calculated using Kaplan-Meier estimate and Greenwood Formula. A generalized Brookmeyer and Crowley method is used to construct a log-log-transformed 95% CI.
Time Frame
Cycle 1 (Day 1) to death, or date of study cutoff, (14 Nov 2014), up to 3 years
Title
Objective Response Rate (ORR)
Description
Objective response rate was defined as the percentage of participants who had a best overall rate (BOR) of CR or PR. Tumor assessment was performed at Week 6 and Week 12 after the start of study treatment, and every six weeks thereafter. The BOR of CR and PR in this study required confirmation by a subsequent assessment of response at least four weeks (28 days) later. CR and PR were determined by the Investigator and IRC using RECIST v1.1 for target lesions assessed by MRI/CT scans. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. A 95% CI was calculated using exact method of binomial distribution.
Time Frame
Date of CR or PR to the date of PD or death, whichever is first, or date of study cutoff (14 Nov 2014), up to 3 years
Title
Disease Control Rate (DCR)
Description
Disease control rate was defined as the percentage of participants who had BOR of CR + PR + SD. BOR of SD must have manifested at least five weeks (35 days) after the first dose of study treatment. Tumor assessment was performed at Week 6 and Week 12 after the start of treatment, and every six weeks thereafter. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of the longest diameter since the treatment started. A 95% CI was calculated using exact method of binomial distribution.
Time Frame
Date of CR, PR, or SD to date of PD or death, whichever is first, or date of study cutoff (14 Nov 2014), up to 3 years
Title
Clinical Benefit Rate (CBR)
Description
CBR was defined as the percentage of participants who had a BOR of CR + PR + dSD (duration of SD greater than or equal to 11 weeks [77 days] after the first dose of study treatment). Tumor assessment was performed at Week 6 and Week 12 after the start of study treatment, and every six weeks thereafter. For participants whose BOR was SD, the duration of SD was defined as the time from the date of the first dose of study treatment to the first documented PD or death, whichever occurred first (i.e., same definition of PFS). If the dSD was censored at a time less than 11 weeks, the participant was considered as not having a clinical benefit. A 95% CI was calculated using exact method of binomial distribution.
Time Frame
First dose of study treatment to the date of CR, PR, or dSD to date of PD or death, whichever is first, or date of study cutoff (14 Nov 2014), up to 3 years
Title
Durable Stable Disease (SD) Rate (dSDR)
Description
Durable stable disease rate was defined as the percentage of participants who manifested durable stable disease (the duration of stable disease for greater than or equal to eleven weeks) and was estimated based on the tumor response assessments performed according to RECIST v1.1. Tumor assessment was performed at Week 6 and Week 12 after the start of study treatment, and every six weeks thereafter. A 2-sided 95% CI was calculated using the exact method of binomial distribution.
Time Frame
Date of dSD to date of PD or death, whichever is first, or date of study cutoff (24 Nov 2014), up to 3 years
Title
Best Overall Response (BOR)
Description
The best overall response categories (CR, PR, SD [including non-CR/non-PD], PD, not evaluable [NE], and unknown [UNK]) were derived based on time point tumor responses during the study as assessed by the IRC as well as the investigator. Tumor assessment was performed at Week 6 and Week 12 after the start of study treatment, and every six weeks thereafter. BOR of SD must have occurred at least 35 days (at least 5 weeks) after the first dose of study drug. If a participant had a BOR of non-CR/non-PD, the participant's BOR was grouped with the SD category.
Time Frame
Date of CR, PR, SD to PD or death of any cause, whichever is first, or date of study cutoff (14 Nov 2014), or up to 3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
Histologically or cytologically confirmed soft tissue sarcoma of high or intermediate grade
Documented evidence of advanced or metastatic soft tissue sarcoma, not amenable to surgery or radiotherapy
Within 6 months from the radiographic evidence of disease progression by RECIST criteria in the last chemotherapy regimen for advanced or metastatic soft tissue sarcoma
Presence of measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Subjects who received at least one standard chemotherapy for advanced soft tissue sarcoma (an anthracycline or an ifosfamide monotherapy, or a combination therapy)
Subjects aged ≥ 20 years at the time of informed consent
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
Adequate organ function
Voluntary agreement to provide written informed consent
Exclusion Criteria
A history of malignancies or recurrence within 5 years after the remission
Significant cardiovascular impairment
Any serious concomitant illness or infection requiring treatment.
Hypersensitivity to either halichondrin B or halichondrin B chemical derivatives or both.
Subjects who have previously participated in a study with eribulin (whether treated with eribulin or not).
Any medical or other condition which, in the opinion of the principal investigator, will preclude participation in a clinical trial.
Subjects who have received any anti-cancer therapy, including surgery, radiotherapy, immunotherapy, cytotoxic, hormonal, biological (including humanized antibodies) and targeted agents within 21 days, or any investigational agent within 30 days, prior to the first dose of study drug.
Subjects who have not recovered from toxicities as a result of prior anti-cancer therapy to ≤ Grade 1, according to Common Terminology Criteria for Adverse Events (CTCAE), except for peripheral neuropathy of Grade 2 and alopecia.
Subjects with known cerebral metastases with clinical symptoms or requiring treatment.
Pre-existing peripheral neuropathy > CTCAE Grade 2.
Female subjects must not be pregnant with a negative by the pregnancy test at Screening, or breastfeeding.
Subjects participating in other clinical trials
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hiroshi Obaishi
Organizational Affiliation
Eisai Co., Ltd.
Official's Role
Study Director
Facility Information:
City
Nagoya
State/Province
Aichi
Country
Japan
City
Kashiwa
State/Province
Chiba
Country
Japan
City
Hidaka
State/Province
Hokkaido
Country
Japan
City
Sapporo
State/Province
Hokkaido
Country
Japan
City
Tsu
State/Province
Mie
Country
Japan
City
Suita
State/Province
Osaka
Country
Japan
City
Bunkyo
State/Province
Tokyo
Country
Japan
City
Chuo-ku
State/Province
Tokyo
Country
Japan
City
Shinjuku
State/Province
Tokyo
Country
Japan
City
Fukuoka
Country
Japan
City
Okayama
Country
Japan
City
Osaka
Country
Japan
12. IPD Sharing Statement
Learn more about this trial
An Open-label, Multicenter, Phase 2 Study to Evaluate the Efficacy and Safety of Eribulin Mesylate in Previously Treated Subjects With Advanced or Metastatic Soft Tissue Sarcoma (Study E7389-J081-217)
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