We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03248492
Recruitment Status : Recruiting
First Posted : August 14, 2017
Last Update Posted : December 12, 2017
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
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 Design

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: Double (Participant, Investigator)
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
U.S. FDA Resources

Arms and Interventions

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


Outcome Measures

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


Eligibility Criteria

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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
Contacts and Locations

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

Locations
United States, Alaska
Alaska Urological Institute dba Alaska Clinical Research Center Recruiting
Anchorage, Alaska, United States, 99508
Contact: Site Coordinator    907-276-1455    twyckoff@akmed.com   
United States, California
Sharp Clinical Oncology Research Recruiting
San Diego, California, United States, 92123
Contact: Principal Investigator    858-939-5052    charles.redfern@sharp.com   
Innovative Clinical Research Institute, LLC Recruiting
Whittier, California, United States, 90603
Contact: Site Coordinator    562-693-4477    kbettino@airesearch.us   
United States, Florida
Specialist Global Research Recruiting
Hialeah, Florida, United States, 33012
Contact: Principal Investigator    786-290-2571    j.gamon@specialistglobalresearch.com   
Miami Cancer Institute at Baptist Health, Inc. Recruiting
Miami, Florida, United States, 33176
Contact: Site Coordinator    786-596-2000    DanieskaS@baptisthealth.net   
United States, Missouri
Washington University School of Medicine Not yet recruiting
Saint Louis, Missouri, United States, 63110
United States, New York
North Shore Hematology Oncology Associates PC DBA NY Cancer and Blood Specialists Recruiting
East Setauket, New York, United States, 11733
Contact: Site Coordinator    631-751-3000    researchpi@nycancer.com   
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Site Coordinator    646-888-4564    modis@mskcc.org   
United States, Ohio
University of Cincinnati Medical Center Recruiting
Cincinnati, Ohio, United States, 45267
Contact: Principal Investigator    513-584-0436    charifm@ucmail.uc.edu   
United States, Pennsylvania
Allegheny General Hospital Recruiting
Pittsburgh, Pennsylvania, United States, 15212
Contact: Principal Investigator    412-359-6147    jane.raymond@ahn.org   
United States, Texas
Accurate Clinical Management, LLC Recruiting
Baytown, Texas, United States, 77521
Contact: Principal Investigator    281-422-7179    dbatista@accurateclinicalresearch.com   
Japan
NHO Shikoku Cancer Center Not yet recruiting
Matsuyama, Ehime-Ken, Japan, 791-0280
Contact: see Central Contact         
Toranomon Hospital Not yet recruiting
Minato-Ku, Tokyo-To, Japan, 105-8470
Contact: see Central Contact         
Aichi Cancer Center Hospital Recruiting
Aichi, Japan, 464-8681
Contact: see Central Contact         
NHO Kyushu Cancer Center Recruiting
Fukuoka, Japan, 811-1395
Contact: see Central Contact         
Hakuaikai Sagara Hospital Recruiting
Kagoshima, Japan, 892-0833
Contact: see Central Contact         
Kanagawa Cancer Center Recruiting
Kanagawa, Japan, 241-0815
Contact: see Central Contact         
National Cancer Center Hospital East Recruiting
Kashiwa, Japan, 277-8577
Contact: see Central Contact         
Kindai University Hospital Recruiting
Osaka, Japan, 589-8511
Contact: see Central Contact         
National Cancer Center Hospital Recruiting
Tokyo, Japan, 104-0045
Contact: Site Coordinator    +81 35200111    chiken_CT@ml.res.ncc.go.jp   
Cancer Institute Hospital of JFCR Recruiting
Tokyo, Japan, 135-8550
Contact: see Central Contact         
Sponsors and Collaborators
Daiichi Sankyo, Inc.
Daiichi Sankyo Co., Ltd.
Investigators
Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
More Information

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: December 12, 2017
Last Verified: December 2017

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