NCT03366428

Brief Summary

This study will look at the effect on the QTc interval and pharmacokinetics after multiple dosing in subjects with HER2-expressing metastatic and/or unresectable breast cancer.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
51

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Dec 2017

Typical duration for phase_1

Geographic Reach
1 country

7 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 4, 2017

Completed
4 days until next milestone

First Posted

Study publicly available on registry

December 8, 2017

Completed
18 days until next milestone

Study Start

First participant enrolled

December 26, 2017

Completed
11 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 5, 2018

Completed
2.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 19, 2021

Completed
4 months until next milestone

Results Posted

Study results publicly available

June 14, 2021

Completed
Last Updated

April 12, 2022

Status Verified

March 1, 2022

Enrollment Period

11 months

First QC Date

December 4, 2017

Results QC Date

May 17, 2021

Last Update Submit

March 17, 2022

Conditions

Malignant Neoplasm of Breast

Keywords

HER2Breast cancerOncologyAntibody drug conjugateADC

Outcome Measures

Primary Outcomes (5)

  • Changes in QTcF After Treatment With DS-8201a in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer

    The number of participants with notable electrocardiogram changes meeting predefined criteria is being reported.

    Screening (within 7 days before enrollment) up to Cycle 3 Day 15 (each cycle is 21 days)

  • Pharmacokinetic Parameters of Maximum Serum Concentration (Cmax) After Cycle 1 and Cycle 3 Treatments With DS-8201a in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer

    Maximum serum concentration (Cmax) of DS-8201a and total anti-HER2 antibody was assessed.

    Cycles 1 and 3: Day 1: before infusion (BI), end of infusion (EOI), 2 hours, 4 hours, 7 hours; Days 2 and 4: 24 hours, 72 hours; Days 8 and 15; Cycle 2: Day 1 BI, EOI; Cycles 4, 6, and 8: Day 1 BI and EOI (each cycle is 21 days)

  • Pharmacokinetic Parameters of Maximum Serum Concentration (Cmax) of MAAA-1181 After Cycle 1 and Cycle 3 Treatments With DS-8201a in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer

    Maximum serum concentration (Cmax) of MAAA-1181 was assessed.

    Cycles 1 and 3: Day 1: before infusion (BI), end of infusion (EOI), 2 hours, 4 hours, 7 hours; Days 2 and 4: 24 hours, 72 hours; Days 8 and 15; Cycle 2: Day 1 BI, EOI; Cycles 4, 6, and 8: Day 1 BI and EOI (each cycle is 21 days)

  • Pharmacokinetic Parameters Area Under the Concentration-Time Curve After Cycle 1 and Cycle 3 Treatments With DS-8201a in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer

    Area under the concentration versus-time curve from time 0 to the last quantifiable concentration (AUClast) and during the dosing interval (AUCtau) of DS-8201a and total anti-HER2 antibody were assessed.

    Cycles 1 and 3: Day 1: before infusion (BI), end of infusion (EOI), 2 hours, 4 hours, 7 hours; Days 2 and 4: 24 hours, 72 hours; Days 8 and 15; Cycle 2: Day 1 BI, EOI; Cycles 4, 6, and 8: Day 1 BI and EOI (each cycle is 21 days)

  • Pharmacokinetic Parameters Area Under the Concentration-Time Curve of MAAA-1181 After Cycle 1 and Cycle 3 Treatments With DS-8201a in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer

    Area under the concentration versus-time curve from time 0 to the last quantifiable concentration (AUClast) and during the dosing interval (AUCtau) were assessed.

    Cycles 1 and 3: Day 1: before infusion (BI), end of infusion (EOI), 2 hours, 4 hours, 7 hours; Days 2 and 4: 24 hours, 72 hours; Days 8 and 15; Cycle 2: Day 1 BI, EOI; Cycles 4, 6, and 8: Day 1 BI and EOI (each cycle is 21 days)

Secondary Outcomes (3)

  • Objective Response Rate Based on The Investigator's Assessment (Unconfirmed) Following DS-8201a Treatment in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer

    Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 12 months post-dose

  • Objective Response Rate Based on The Investigator's Assessment (Unconfirmed) Following DS-8201a Treatment in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer

    Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 38 months post-dose

  • Treatment-Emergent Adverse Events of Any Grade by System Organ Classes and Preferred Term Following DS-8201a Treatment in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer

    Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to approximately 12 months post-dose

Study Arms (1)

All Participants

EXPERIMENTAL

All participants will receive DS-8201a by intravenous infusion

Drug: DS-8201a

Interventions

DS-8201aDRUG

DS-8201a is supplied as a lyophilized powder which is reconstituted for infusion

Also known as: Experimental product
All Participants

Eligibility Criteria

Age20 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

Kanagawa Cancer Center

Yokohama, Kanagawa, 241-8515, Japan

Location

National Cancer Center Hospital

Chuo Ku, Tokyo, 104-0045, Japan

Location

The Cancer Institute Hospital of Japanese Foundation For Cancer Research

Koto-Ku, Tokyo, 135-8550, Japan

Location

Toranomon Hospital

Minato-Ku, Tokyo, 105-8470, Japan

Location

National Hospital Organization Kyushu Cancer Center

Fukuoka, 811-1395, Japan

Location

Social Medical Corporation Hakuaikai Sagara Hospital

Kagoshima, 892-0833, Japan

Location

Shizuoka Cancer Center

Shizuoka, 411-8777, Japan

Location

Related Publications (1)

  • Shimomura A, Takano T, Takahashi S, Sagara Y, Watanabe J, Tokunaga E, Shinkai T, Kamio T, Kikumori K, Kamiyama E, Fujisaki Y, Saotome D, Yamashita T. Effect of Trastuzumab Deruxtecan on QT/QTc Interval and Pharmacokinetics in HER2-Positive or HER2-Low Metastatic/Unresectable Breast Cancer. Clin Pharmacol Ther. 2023 Jan;113(1):160-169. doi: 10.1002/cpt.2757. Epub 2022 Oct 18.

    PMID: 36164935DERIVED

MeSH Terms

Conditions

Breast NeoplasmsNeoplasms

Interventions

trastuzumab deruxtecan

Condition Hierarchy (Ancestors)

Neoplasms by SiteBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Results Point of Contact

Title
Contact for Clinical Trial Information
Organization
Daiichi Sankyo
CTRinfo@dsi.com
908-992-6400

Study Officials

  • Global Clinical Leader

    Daiichi Sankyo

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 4, 2017

First Posted

December 8, 2017

Study Start

December 26, 2017

Primary Completion

December 5, 2018

Study Completion

February 19, 2021

Last Updated

April 12, 2022

Results First Posted

June 14, 2021

Record last verified: 2022-03

Data Sharing

IPD Sharing
Will share

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/

Shared Documents
STUDY PROTOCOL, SAP, 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.
More information

Locations

JP(7)