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Phase 1 Study to Evaluate the Effect of DS-8201a on the QT/QTc Interval in HER2-Expressing Breast Cancer

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ClinicalTrials.gov Identifier: NCT03366428
Recruitment Status : Recruiting
First Posted : December 8, 2017
Last Update Posted : July 2, 2018
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. )

Brief Summary:
This study will look at the effect of DS-8201a on heart rate and the movement of the drug through the body (pharmacokinetics) in participants with a certain type of breast cancer (HER2).

Condition or disease Intervention/treatment Phase
Malignant Neoplasm of Breast Drug: DS-8201a Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1, Multicenter, Open-label, Multiple-dose Study of DS-8201a to Assess the Effect on the QT Interval and Pharmacokinetics in Subjects With HER2-expressing Metastatic and/or Unresectable Breast Cancer
Actual Study Start Date : December 26, 2017
Estimated Primary Completion Date : September 2018
Estimated Study Completion Date : April 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: All Participants
All participants will receive DS-8201a by intravenous infusion
Drug: DS-8201a
DS-8201a is supplied as a lyophilized powder which is reconstituted for infusion
Other Name: Experimental product




Primary Outcome Measures :
  1. Average baseline-adjusted QT interval corrected for heart rate by Fridericia's formula (QTcF ) [ Time Frame: Cycle 1 to 3 (approximately 63 days) ]
    The QT intervals will be corrected for heart rate by Fridericia's formula (QTcF = QT/[RR]1/3). The baseline QTcF interval for each subject will be subtracted from QTcF interval to create a baseline-adjusted QTcF interval.

  2. Maximum Concentration (Cmax) [ Time Frame: Samples collected: Cycles 1 and 3 (Days 1, 2, 4, 8,15, 22); Cycles 2, 4, 6 and 8 (Days 1 and 22) ]
    Categories: DS-8201a, total anti-HER2 antibody, and MAAA-1181a

  3. Time to Cmax (Tmax) [ Time Frame: Samples collected: Cycles 1 and 3 (Days 1, 2, 4, 8,15, 22); Cycles 2, 4, 6 and 8 (Days 1 and 22) ]

    Categories: DS-8201a, total anti-HER2 antibody, and MAAA-1181a

    Tmax is the time it takes to reach the maximum concentration


  4. Area under the drug concentration time curve (AUC) at the last observation (AUClast) [ Time Frame: Samples collected: Cycles 1 and 3 (Days 1, 2, 4, 8,15, 22); Cycles 2, 4, 6 and 8 (Days 1 and 22) ]
    Categories: DS-8201a, total anti HER2 antibody, and MAAA-1181a

  5. AUC extrapolated to infinity (AUCinf) [ Time Frame: Samples collected: Cycles 1 and 3 (Days 1, 2, 4, 8,15, 22); Cycles 2, 4, 6 and 8 (Days 1 and 22) ]

    Categories: DS-8201a, total anti HER2 antibody, and MAAA-1181a

    AUCinf is calculated as the area under the curve from time 0 to infinity


  6. Half-life (T1/2) [ Time Frame: Samples collected: Cycles 1 and 3 (Days 1, 2, 4, 8,15, 22); Cycles 2, 4, 6 and 8 (Days 1 and 22) ]

    Categories: DS-8201a, total anti HER2 antibody, and MAAA-1181a

    T1/2 is the time it takes for half of the drug to leave the body


  7. Clearance (CL) of DS8201a [ Time Frame: Samples collected: Cycles 1 and 3 (Days 1, 2, 4, 8,15, 22); Cycles 2, 4, 6 and 8 (Days 1 and 22) ]
    CL is derived from the curve of concentration versus time

  8. Volume of DS-8201a at steady state (Vss) [ Time Frame: Samples collected: Cycles 1 and 3 (Days 1, 2, 4, 8,15, 22); Cycles 2, 4, 6 and 8 (Days 1 and 22) ]
    Vss is the apparent volume of distribution at steady state


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: within 17 months ]
    ORR is defined as the percentage of participants who achieve a best overall response of complete response (CR) or partial response (PR), as assessed by the investigator based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1

  2. Disease Control Rate (DCR) [ Time Frame: within 17 months ]
    DCR is defined as the percentage of participants who achieve a best overall response of CR or PR or stable disease (SD)



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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has a pathologically documented unresectable or metastatic breast cancer with HER2 expression (immunohistochemistry [IHC] 3+, IHC 2+, IHC 1+ and/or in situ hybridization [ISH] +) that is refractory to or intolerable with standard treatment, or for which no standard treatment is available
  • Has a left ventricular ejection fraction (LVEF) ≥ 50%
  • Has an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1

Exclusion Criteria:

  • Has a medical history of myocardial infarction within 6 months before enrollment
  • Has a medical history of ventricular arrhythmias, other than rare occasional premature ventricular contractions
  • Has uncontrolled or significant cardiovascular disease
  • Has any other history or condition that might compromise:

    1. Safety 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): NCT03366428


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

Locations
Japan
Kanagawa Cancer Center Recruiting
Yokohama, Kanagawa, Japan, 241-8515
National Cancer Center Hospital Recruiting
Chuo Ku, Tokyo, Japan, 104-0045
The Cancer Institute Hospital of Japanese Foundation For Cancer Research Recruiting
Koto-Ku, Tokyo, Japan, 135-8550
Toranomon Hospital Recruiting
Minato-Ku, Tokyo, Japan, 105-8470
National Hospital Organization Kyushu Cancer Center Recruiting
Fukuoka, Japan, 811-1395
Social Medical Corporation Hakuaikai Sagara Hospital Recruiting
Kagoshima, Japan, 892-0833
Shizuoka Cancer Center Recruiting
Shizuoka, Japan, 411-8777
Sponsors and Collaborators
Daiichi Sankyo Co., Ltd.
Investigators
Study Director: Global Clinical Leader Daiichi Sankyo, Inc.

Responsible Party: Daiichi Sankyo Co., Ltd.
ClinicalTrials.gov Identifier: NCT03366428     History of Changes
Other Study ID Numbers: DS8201-A-J102
First Posted: December 8, 2017    Key Record Dates
Last Update Posted: July 2, 2018
Last Verified: June 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 https://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/Study-Sponsors-DS.aspx
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
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://www.clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-DS.aspx

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

Keywords provided by Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. ):
HER2
Breast cancer
Oncology
Antibody drug conjugate
ADC

Additional relevant MeSH terms:
Breast Diseases
Breast Neoplasms
Neoplasms
Neoplasms by Site
Skin Diseases
Camptothecin
Immunoconjugates
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs