Phase 1 Study to Evaluate the Effect of DS-8201a on the QT/QTc Interval and Pharmacokinetics in HER2-Expressing Breast Cancer
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| ClinicalTrials.gov Identifier: NCT03366428 |
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Recruitment Status :
Completed
First Posted : December 8, 2017
Results First Posted : June 14, 2021
Last Update Posted : April 12, 2022
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Sponsor:
Daiichi Sankyo Co., Ltd.
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. )
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Malignant Neoplasm of Breast | Drug: DS-8201a | Phase 1 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 51 participants |
| Allocation: | N/A |
| 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 |
| Actual Primary Completion Date : | December 5, 2018 |
| Actual Study Completion Date : | February 19, 2021 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Breast cancer
MedlinePlus related topics:
Breast Cancer
| Arm | Intervention/treatment |
|---|---|
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Experimental: All Participants
All participants will receive DS-8201a by intravenous infusion
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Drug: DS-8201a
DS-8201a is supplied as a lyophilized powder which is reconstituted for infusion
Other Name: Experimental product |
Primary Outcome Measures :
- Changes in QTcF After Treatment With DS-8201a in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer [ Time Frame: Screening (within 7 days before enrollment) up to Cycle 3 Day 15 (each cycle is 21 days) ]The number of participants with notable electrocardiogram changes meeting predefined criteria is being reported.
- 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 [ Time Frame: 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) ]Maximum serum concentration (Cmax) of DS-8201a and total anti-HER2 antibody was assessed.
- 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 [ Time Frame: 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) ]Maximum serum concentration (Cmax) of MAAA-1181 was assessed.
- 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 [ Time Frame: 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) ]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.
- 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 [ Time Frame: 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) ]Area under the concentration versus-time curve from time 0 to the last quantifiable concentration (AUClast) and during the dosing interval (AUCtau) were assessed.
Secondary Outcome Measures :
- 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 [ Time Frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 12 months post-dose ]Objective response rate (ORR) was defined as unconfirmed complete response (CR) and partial response (PR) as assessed by the investigator based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.
- 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 [ Time Frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 38 months post-dose ]Objective response rate (ORR) was defined as unconfirmed complete response (CR) and partial response (PR) as assessed by the investigator based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.
- 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 [ Time Frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to approximately 12 months post-dose ]Adverse events (AEs) were to be coded using MedDRA Version 20.1 and assigned severity grades based on Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. A treatment-emergent adverse event (TEAE) was defined as an AE that occurred, having been absent before the first dose of study drug, or had worsened in severity or seriousness after initiating the study drug until 47 days after last dose of study drug.
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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
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
Locations
| Japan | |
| Kanagawa Cancer Center | |
| Yokohama, Kanagawa, Japan, 241-8515 | |
| National Cancer Center Hospital | |
| Chuo Ku, Tokyo, Japan, 104-0045 | |
| The Cancer Institute Hospital of Japanese Foundation For Cancer Research | |
| Koto-Ku, Tokyo, Japan, 135-8550 | |
| Toranomon Hospital | |
| Minato-Ku, Tokyo, Japan, 105-8470 | |
| National Hospital Organization Kyushu Cancer Center | |
| Fukuoka, Japan, 811-1395 | |
| Social Medical Corporation Hakuaikai Sagara Hospital | |
| Kagoshima, Japan, 892-0833 | |
| Shizuoka Cancer Center | |
| Shizuoka, Japan, 411-8777 | |
Sponsors and Collaborators
Daiichi Sankyo Co., Ltd.
AstraZeneca
Investigators
| Study Director: | Global Clinical Leader | Daiichi Sankyo, Inc. |
Study Documents (Full-Text)
Documents provided by Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. ):
Documents provided by Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. ):
Study Protocol and Statistical Analysis Plan [PDF] July 3, 2020
| Responsible Party: | Daiichi Sankyo Co., Ltd. |
| ClinicalTrials.gov Identifier: | NCT03366428 |
| Other Study ID Numbers: |
DS8201-A-J102 173791 ( Registry Identifier: JAPIC CTI ) |
| First Posted: | December 8, 2017 Key Record Dates |
| Results First Posted: | June 14, 2021 |
| Last Update Posted: | April 12, 2022 |
| Last Verified: | March 2022 |
| 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://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 Statistical Analysis Plan (SAP) 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/ |
| 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. ):
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HER2 Breast cancer Oncology Antibody drug conjugate ADC |
Additional relevant MeSH terms:
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Breast Neoplasms Neoplasms Neoplasms by Site Breast Diseases Skin Diseases |