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DS-8201a in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer

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ClinicalTrials.gov Identifier: NCT03248492
Recruitment Status : Recruiting
First Posted : August 14, 2017
Last Update Posted : July 17, 2018
Sponsor:
Collaborator:
Daiichi Sankyo Co., Ltd.
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Brief Summary:
Some HER-2 breast cancer patients do not respond or build resistance 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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: DS-8201a Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 230 participants
Allocation: Randomized
Intervention Model: Sequential 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 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
Official Title: 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
Actual Study Start Date : August 25, 2017
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : February 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: DS-8201a Low Dose
T-DM1 resistant/refractory (R/R) patients in the low dose treatment group
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

Experimental: DS-8201a Medium Dose
T-DM1 resistant/refractory (R/R) patients in the medium dose treatment group
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

Experimental: DS-8201a High Dose
T-DM1 resistant/refractory (R/R) patients in the high dose treatment group
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

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
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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Duration of response [ Time Frame: within 22 months ]
    Length of time response continued

  2. 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

  3. Disease control rate (DCR) [ Time Frame: within 22 months ]
    Percentage of participants with controlled disease

  4. Clinical benefit rate (CBR) [ Time Frame: within 22 months ]
    Percentage of participants receiving clinical benefit from the treatment

  5. Progression-free survival [ Time Frame: within 22 months ]
    Percentage of participants still alive without the disease getting worse

  6. Overall survival (OS) [ Time Frame: at 22 months ]
    Percentage of participants still alive

  7. 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

  8. Maximum plasma/serum concentration (Cmax) [ Time Frame: within 21 days ]
    Categories: DS-8201a, total anti-HER2 antibody and MAAA-1181a

  9. Time to Cmax (Tmax) [ Time Frame: within 21 days ]
    Categories: DS-8201a, total anti-HER2 antibody and MAAA-1181a

  10. 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

  11. 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03248492


Contacts
Contact: (For Sites in Asia Only) Daiichi Sankyo Contact for Clinical Trial Information +81-3-6225-1111(M-F 9-5 JST) dsclinicaltrial@daiichisankyo.co.jp

  Show 91 Study Locations
Sponsors and Collaborators
Daiichi Sankyo, Inc.
Daiichi Sankyo Co., Ltd.
Investigators
Study Director: Global Clinical Leader Daiichi Sankyo, Inc.

Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT03248492     History of Changes
Other Study ID Numbers: DS8201-A-U201
2016-004986-18 ( EudraCT Number )
JapicCTI-173693(en) ( Registry Identifier: JapicCTI )
First Posted: August 14, 2017    Key Record Dates
Last Update Posted: July 17, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
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 http://www.clinicalstudydatarequest.com. 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://www.clinicalstudydatarequest.com/Study-Sponsors-DS-Details.aspx
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Studies for which the medicine and indication have received EU and US marketing approval on or after 01 January 2014 or by the US or EU Health Authorities when regulatory submissions in both 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 and the European Union 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://www.clinicalstudydatarequest.com/Study-Sponsors-DS-Details.aspx

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Daiichi Sankyo, Inc.:
HER-2 positive breast cancer
Metastatic or Unresectable
Resistant or refractory to T-DM1

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Ado-trastuzumab emtansine
Camptothecin
Immunoconjugates
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Immunologic Factors
Physiological Effects of Drugs