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Completed

NCT Number: NCT03366428

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

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.

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Key information

Conditions

Malignant Neoplasm of Breast Breast Diseases Breast Neoplasms Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases

Age range

20 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Kanagawa Cancer Center, Yokohama, Kanagawa, Japan

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

DS-8201a

Drug

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

Other names: Experimental product

Primary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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 outcomes

  1. 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.

  2. 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.

  3. 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.

Sponsors and collaborators

Lead sponsor

Daiichi Sankyo Co., Ltd.

Industry

Collaborators

  • AstraZeneca

Registry information

Official study 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

Important dates

Study start
2017
Primary completion
2018
Study completion
2021
First posted
Dec 8, 2017
Registry last updated
Apr 12, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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