E7389 Administered as an IV Bolus Infusion Day 1 and Day 8 Every 3 Weeks in Pre-Treated Patients With Advanced and/or Metastatic Soft Tissue Sarcoma
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|ClinicalTrials.gov Identifier: NCT00413192|
Recruitment Status : Completed
First Posted : December 19, 2006
Results First Posted : March 22, 2017
Last Update Posted : April 26, 2017
|Condition or disease||Intervention/treatment||Phase|
|Soft Tissue Sarcoma||Drug: E7389||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||128 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of E7389 Administered as an IV Bolus Infusion Day 1 and Day 8 Every 3 Weeks in Pre-Treated Patients With Advanced and/or Metastatic Soft Tissue Sarcoma|
|Study Start Date :||January 2007|
|Actual Primary Completion Date :||June 2012|
|Actual Study Completion Date :||February 2013|
1.4 mg/m^2 administered as an intravenous (I.V.) bolus infusion on Days 1 and 8 of every 21 days.
- Progression Free Survival (PFS) at 12 Weeks [ Time Frame: Week 12 ]PFS was determined from the Week 12 visit tumor scan and the participant's date of death. Progression was defined as complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), early death from any cause, or not assessable according to Response Evaluation Criteria In Solid Tumors (RECIST). CR defined as the loss of all target lesions. PR defined as ≥ 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD. PD defined as ≥ 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since treatment started or the appearance of new lesions. SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD since treatment started. The number and percentage of successes were summarized by stratum and overall, together with 95% 2-sided confidence intervals (CIs) for the percentage of successes.
- Overall Progression Free Survival [ Time Frame: First dose of study drug to the date of disease progression or date of death, whichever occurs first, or date of study cut-off 28 Jun 2012, up to 5.5 years ]Overall PFS was determined from any evidence that the participant had progressed, along with whether or not the participant was still alive at the end of the study. Tumors were evaluated every 6 weeks during treatment, and at least 4 weeks after the first observation of a complete or partial response. After discontinuation of study drug, participants without PD were re-evaluated every 12 weeks, unless a new anticancer therapy was started. Participants were considered as having progressed if they were classed as PD at Week 12, or had a best overall response (BOR) of PD, or had a date of progression, if they discontinued due to PD, died due to PD, or if the PI had recorded a date of progression. A participant was determined progression free if they were alive without PD at the time of study cut-off. The number and percentage of successes were summarized by stratum and overall, together with 95% 2-sided CIs for the percentage of successes.
- Objective Response Rate (ORR) [ Time Frame: Date of first dose of study drug until documentation of CR or PR, or up to data cutoff 28 Jun 2012, up to approximately 5.5 years ]ORR was defined as the percentage of participants in the analysis set who had a BOR of CR or PR based on RECIST v. 1.0 for target lesions. Tumors were assessed using x-rays, magnetic resonance imaging (MRI), or computed tomography (CT) scans, or both, as appropriate. ORR was documented and confirmed by two measurements taken at least 4 weeks apart. CR was defined as the disappearance of all target lesions. PR defined as ≥ 30% decrease in the sum of LD of target lesions taking as reference the baseline sum LD. Best overall response was derived using the same hierarchy as used when determining the PFS status at Week 12. No adjustments were made for participants who started further anticancer therapy prior to disease progression. 95% CIs were calculated using the exact method of binomial distribution. ORR = CR + PR
- Clinical Response Benefit (CRB) [ Time Frame: Date of first dose of study drug to documentation of CR, PR, or SD, or until data cutoff date 28 Jun 2012, up to approximately 5.5 years ]CRB was defined as the percentage of participants with a BOR of CR or PR or SD as defined by RECIST, described previously. BOR was derived using the same hierarchy as used when determining the status at Week 12. No adjustments were made for participants who started further anticancer therapy prior to disease progression. 95% CIs were calculated using the exact method of binomial distribution. CRB = CR + PR + SD
- Time to Onset of Response [ Time Frame: Date of first dose of study drug to date of first documented CR or PR, or until data cutoff date 28 Jun 2012, up to approximately 5.5 years ]Time to onset of response could be calculated only if a participant achieved an objective response (BOR of CR or PR as defined previously). Participants who never achieved CR or PR were not included in the Kaplan-Meier survival estimates for the time to onset of response by strata. Given the small number of participants with these responses and the large variation in time to onset of response between participants, no comparison could be made among the strata.
- Duration of Response [ Time Frame: Date of first documented CR or PR until the date of first document disease progression (or death), or up to data cutoff 28 Jun 2012, up to approximately 5.5 years ]Duration of response could be calculated only if a participant achieved a BOR of CR or PR, as defined previously. For consistency with the formula used by the European Organization for Research and Treatment of Cancer (EORTC), the duration was derived as "day of event minus day of first documented CR or PR" (one was not added to the calculation). Participants who were alive without documented progression had their duration of response censored at the day of last follow-up for progression. Participants who never achieved CR or PR were not included in the Kaplan-Meier survival estimates for the duration of response by strata. No adjustment was made for participants who started further anticancer therapy prior to disease progression.
- Overall Survival (OS) [ Time Frame: Date of first dose of study drug to date of death from any cause, or up to cut-off date of 28 Jun 2012, up to approximately 5.5 years ]Participants still alive at the end of the study had their time to event censored at the day last known to be alive. Participants lost to follow-up were also censored at the date last known to be alive. 95% CIs for the percentage of participants still alive at the end of the study were presented as described for the primary endpoint, PFS at Week 12.
- Summary of Adverse Events (AEs) [ Time Frame: Day 1 of study treatment until progressive disease, or up to cut-off date of 28 Jun 2012, up to approximately 5.5 years ]Treatment-emergent adverse events (TEAEs) and serious adverse events were reported. TEAEs are defined as an adverse event (AE) that emerged during treatment, having been absent at baseline or: reemerged during treatment, having been present at pretreatment (baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. All AEs and SAEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. A participant was counted only once within a System Organ Class (SOC) and preferred term (PT), even if the participant experienced more than one TEAE with a specific SOC and PT. Participants were summarized by treatment group according to the worst CTCAE grade assigned for each PT. Treatment-related TEAEs included TEAEs that were considered by the investigator to be possibly or probably related to study drug or TEAEs with a missing relationship.
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Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00413192
|Brussels, Belgium, BE 1000|
|Leuven, Belgium, BE 3000|
|Aarhus, Denmark, DK 8000|
|Herlev, Denmark, DK 2730|
|Bordeaux, France, 33076|
|Lyon, France, 69008|
|Marseille, France, 13385|
|Villejuif, France, 94805|
|Bad Saarow, Germany, 15526|
|Dresden, Germany, DE 01307|
|Essen, Germany, DE 45122|
|Hannover, Germany, DE 30625|
|Mannheim, Germany, DE 68135|
|Tuebingen, Germany, DE 72076|
|Warsaw, Poland, 02 781|