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A Study of DS-8201a in Metastatic Breast Cancer Previously Treated With Trastuzumab Emtansine (T-DM1)

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ClinicalTrials.gov Identifier: NCT03248492
Recruitment Status : Active, not recruiting
First Posted : August 14, 2017
Results First Posted : February 17, 2020
Last Update Posted : May 26, 2021
Sponsor:
Collaborators:
AstraZeneca
Daiichi Sankyo Co., Ltd.
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Tracking Information
First Submitted Date  ICMJE August 10, 2017
First Posted Date  ICMJE August 14, 2017
Results First Submitted Date  ICMJE January 17, 2020
Results First Posted Date  ICMJE February 17, 2020
Last Update Posted Date May 26, 2021
Actual Study Start Date  ICMJE August 25, 2017
Actual Primary Completion Date March 21, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 17, 2020)
Objective Response Rate as Confirmed by Independent Central Review Following Intravenous Administration of 5.4 mg/kg DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) [ Time Frame: at least 6 months after last participant enrolled received first dose up to 19 months (data cut off) ]
The number of participants with objective response was assessed every six weeks from Cycle 1 Day 1 through discontinuation of treatment, by independent central imaging facility review based on RECIST version 1.1.
Original Primary Outcome Measures  ICMJE
 (submitted: August 10, 2017)
Objective response rate (ORR) per imaging assessment [ Time Frame: within 22 months ]
Percentage of participants with objective response is assessed every six weeks from Cycle 1 Day 1 through disease progression, by independent central imaging facility review based on RECIST version 1.1
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 13, 2020)
  • Objective Response Rate as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) [ Time Frame: at least 6 months after last participant enrolled received first dose up to 19 months (data cut off) ]
    The number of participants with objective response is assessed every six weeks from Cycle 1 Day 1 through discontinuation of treatment. Investigator-assessed objective response rate (ORR) was defined as the proportion of participants who achieved a best overall response of complete response or partial response based on local radiologists/investigators' tumor assessments.
  • Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) [ Time Frame: at least 6 months after last participant enrolled received first dose up to 19 months (data cut off) ]
    Best overall tumor response was defined as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) by the investigator based on RECIST v1.1. Participants who were non-evaluable (NE) are also reported.
  • Disease Control Rate and Clinical Benefit Rate as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) [ Time Frame: at least 6 months after last participant enrolled received first dose up to 19 months (data cut off) ]
    Number of participants with controlled disease and who received clinical benefit from treatment as assessed by independent central review. DCR was defined as the proportion of participants who achieved a best overall response of complete response, partial response, or stable disease. CBR was defined as the proportion of participants who achieved a best overall response of complete response or partial response or more than 6 months of stable disease.
  • Duration of Response (Complete Response or Partial Response) as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) [ Time Frame: at least 6 months after last participant enrolled received first dose up to 19 months (data cut off) ]
    The estimated duration of confirmed response (complete response [CR] or partial response [PR]) was assessed by independent central review. Duration of response was defined as the time interval between the date of first documentation of objective response (CR or PR) and the date of the first objective documentation of disease progression or death due to any cause.
  • Progression-Free Survival Estimate As Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) [ Time Frame: at least 6 months after last participant enrolled received first dose up to 19 months (data cut off) ]
    The point estimate of progression-free survival (PFS) is reported. PFS was defined as the time interval between the date of randomization/registration and the first documentation of disease progression or death due to any cause.
  • Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) [ Time Frame: Baseline up to Week 6, 12, 18, 24, 30, 36 post dose ]
    Best percent change in sum of diameters of measurable tumors was based on RECIST 1.1. The best percent change was defined as the percent change in the smallest sum of diameters from all post-baseline tumor assessments, taking as reference the baseline sum of diameters.
  • Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) [ Time Frame: Day 0 to Day 47 post last dose ]
    TEAEs were assessed by severity and seriousness according to unique criteria. Severity described the intensity of an event and was graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03, where Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL); Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL; Grade 4: Life-threatening consequences; urgent intervention indicated; and Grade 5: Death related to AE. Serious TEAEs were defined as any untoward medical occurrence that at any dose results in death, is life threatening, requires inpatient hospitalization, or causes prolongation of existing hospitalization.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 10, 2017)
  • Duration of response [ Time Frame: within 22 months ]
    Length of time response continued
  • Best percent change in the sum of the longest diameters (SLD) of measurable tumors [ Time Frame: within 22 months ]
    The best percent change from baseline in the SLD will be provided by part/dose group
  • Disease control rate (DCR) [ Time Frame: within 22 months ]
    Percentage of participants with controlled disease
  • Clinical benefit rate (CBR) [ Time Frame: within 22 months ]
    Percentage of participants receiving clinical benefit from the treatment
  • Progression-free survival [ Time Frame: within 22 months ]
    Percentage of participants still alive without the disease getting worse
  • Overall survival (OS) [ Time Frame: at 22 months ]
    Percentage of participants still alive
  • ORR assessed by the investigator based on RECIST version 1.1 [ Time Frame: within 22 months ]
    Percentage of participants with objective response as assessed by the investigator, based on RECIST version 1.1
  • Maximum plasma/serum concentration (Cmax) [ Time Frame: within 21 days ]
    Categories: DS-8201a, total anti-HER2 antibody and MAAA-1181a
  • Time to Cmax (Tmax) [ Time Frame: within 21 days ]
    Categories: DS-8201a, total anti-HER2 antibody and MAAA-1181a
  • Area under the concentration-time curve (AUC) from dosing until the last quantifiable concentration (AUClast) [ Time Frame: within 21 days ]
    Categories: DS-8201a, total anti-HER2 antibody and MAAA-1181a
  • AUC from the time of dosing until day 21 (AUC0-21d) [ Time Frame: at Day 21 ]
    Categories: DS-8201a, total anti-HER2 antibody and MAAA-1181a
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of DS-8201a in Metastatic Breast Cancer Previously Treated With Trastuzumab Emtansine (T-DM1)
Official Title  ICMJE A Phase 2, Multicenter, Open-Label Study of DS-8201a, an Anti-HER2-Antibody Drug Conjugate (ADC) for HER2-Positive, Unresectable and/or Metastatic Breast Cancer Subjects Previously Treated With T-DM1 (DESTINY-Breast01)
Brief Summary Some human epidermal growth factor receptor 2 (HER-2) breast cancer patients do not respond or become resistant to current treatment. DS-8201a is a new experimental product that is a combination of an antibody and a drug. It has not yet been approved for use. DS-8201a may slow down tumor growth. This might improve outcomes for these patients.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
HER2-positive patients will be classified into two groups: T-DM1 resistant/refractory (experimental) and T-DM1 intolerant (exploratory only).
Masking: None (Open Label)
Masking Description:
In Part 1, about 60 trastuzumab emtansine (T-DM1) resistant/refractory patients initially will be randomized into three treatment groups (low, medium and high doses) for Pharmacokinetics (PK), then about another 60 will be randomized into low and high doses to determine recommended dose (RD). After that, about 100 will receive the recommended dose in an open-label continuation stage (Part 2). About 10 TDM-1 intolerant patients will join the continuation stage as an exploratory only arm.
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE Drug: DS-8201a
DS-8201a is sterile lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered as low, medium and high intravenous (IV) doses for Part 1 of the trial. The dose for Part 2 will be determined based on results from Part 1.
Other Name: Experimental product
Study Arms  ICMJE
  • Experimental: DS-8201a Low Dose
    T-DM1 resistant/refractory (R/R) patients in the low dose treatment group
    Intervention: Drug: DS-8201a
  • Experimental: DS-8201a Medium Dose
    T-DM1 resistant/refractory (R/R) patients in the medium dose treatment group
    Intervention: Drug: DS-8201a
  • Experimental: DS-8201a High Dose
    T-DM1 resistant/refractory (R/R) patients in the high dose treatment group
    Intervention: Drug: DS-8201a
  • Exploratory Arm
    In Part 2b- Continuation Stage, about 10 T-DM1 Intolerant patients will receive the DS-8201a recommended dose (RD) as an exploratory arm
    Intervention: Drug: DS-8201a
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: January 17, 2020)
253
Original Estimated Enrollment  ICMJE
 (submitted: August 10, 2017)
230
Estimated Study Completion Date  ICMJE September 30, 2021
Actual Primary Completion Date March 21, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Men or women the age of majority in their country
  • Has pathologically documented breast cancer that:

    1. is unresectable or metastatic
    2. has HER2 positive expression confirmed per protocol
  • Has an adequate tumor sample
  • Has at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
  • Has protocol-defined adequate cardiac, renal and hepatic function
  • Agrees to follow protocol-defined method(s) of contraception

Exclusion Criteria:

  • Has a medical history of myocardial infarction, symptomatic congestive heart failure (CHF) (NYHA classes II-IV), unstable angina or serious cardiac arrhythmia
  • Has a corrected QT interval (QTc) prolongation to > 450 millisecond (ms) in males and > 470 ms in females
  • Has a medical history of clinically significant lung disease
  • Is suspected to have certain other protocol-defined diseases based on imaging at screening period
  • Has history of any disease, metastatic condition, drug/medication use or other condition that might, per protocol or in the opinion of the investigator, compromise:

    1. safety or well-being of the participant or offspring
    2. safety of study staff
    3. analysis of results
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Canada,   France,   Italy,   Japan,   Korea, Republic of,   Spain,   United Kingdom,   United States
Removed Location Countries Germany
 
Administrative Information
NCT Number  ICMJE NCT03248492
Other Study ID Numbers  ICMJE DS8201-A-U201
2016-004986-18 ( EudraCT Number )
JapicCTI-173693(en) ( Registry Identifier: JapicCTI )
DESTINY-Breast01 ( Other Identifier: Daiichi Sankyo and AstraZeneca )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
URL: https://vivli.org/ourmember/daiichi-sankyo/
Responsible Party Daiichi Sankyo, Inc.
Study Sponsor  ICMJE Daiichi Sankyo, Inc.
Collaborators  ICMJE
  • AstraZeneca
  • Daiichi Sankyo Co., Ltd.
Investigators  ICMJE
Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
PRS Account Daiichi Sankyo, Inc.
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP