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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc. ( Eisai Co., Ltd. )
ClinicalTrials.gov Identifier:
NCT01458249
First received: October 21, 2011
Last updated: March 9, 2016
Last verified: March 2016
  Purpose
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).

Condition Intervention Phase
Soft Tissue Sarcoma
Drug: eribulin mesylate
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Progression-free Rate at 12 Weeks (PFR12wks) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Cycle 1 (Day 1) to progressive disease (PD) or death, or date of study cutoff (14 Nov 2014) up to 3 years ] [ Designated as safety issue: No ]
    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) [ Time Frame: Cycle 1 (Day 1) to death, or date of study cutoff, (14 Nov 2014), up to 3 years ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 52
Study Start Date: November 2011
Study Completion Date: February 2016
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: eribulin mesylate 1.4 mg/m^2 Drug: eribulin mesylate
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.
Other Name: E7389

  Eligibility

Ages Eligible for Study:   20 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01458249

Locations
Japan
Nagoya, Aichi, Japan
Kashiwa, Chiba, Japan
Hidaka, Hokkaido, Japan
Sapporo, Hokkaido, Japan
Tsu, Mie, Japan
Suita, Osaka, Japan
Bunkyo, Tokyo, Japan
Chuo-ku, Tokyo, Japan
Shinjuku, Tokyo, Japan
Fukuoka, Japan
Okayama, Japan
Osaka, Japan
Sponsors and Collaborators
Eisai Co., Ltd.
Investigators
Study Director: Hiroshi Obaishi Eisai Co., Ltd.
  More Information

Responsible Party: Eisai Co., Ltd.
ClinicalTrials.gov Identifier: NCT01458249     History of Changes
Other Study ID Numbers: E7389-J081-217 
Study First Received: October 21, 2011
Results First Received: February 7, 2016
Last Updated: March 9, 2016
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Eisai Inc.:
Soft Tissue Sarcoma

Additional relevant MeSH terms:
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on July 25, 2016