Clinical trial NCT03366428: Phase 1 Study to Evaluate the Effect of DS-8201a on the QT/QTc Interval and Pharmacokinetics in HER2-Expressing Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Malignant Neoplasm of Breast
Keywords: HER2
Breast cancer
Oncology
Antibody drug conjugate
ADC
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: AstraZeneca
First posted: 2017-12-08
Enrollment: 51
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Changes in QTcF After Treatment With DS-8201a in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer
timeFrame: Screening (within 7 days before enrollment) up to Cycle 3 Day 15 (each cycle is 21 days)
measure: 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
timeFrame: 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)
measure: 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
timeFrame: 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)
measure: 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
timeFrame: 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)
measure: 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
timeFrame: 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:
measure: 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
timeFrame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 12 months post-dose
measure: 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
timeFrame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 38 months post-dose
measure: 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
timeFrame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to approximately 12 months post-dose
Other outcomes:
Locations:
city: Yokohama
country: Japan
facility: Kanagawa Cancer Center
state: Kanagawa
city: Chuo Ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Koto-Ku
country: Japan
facility: The Cancer Institute Hospital of Japanese Foundation For Cancer Research
state: Tokyo
city: Minato-Ku
country: Japan
facility: Toranomon Hospital
state: Tokyo
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Kagoshima
country: Japan
facility: Social Medical Corporation Hakuaikai Sagara Hospital
city: Shizuoka
country: Japan
facility: Shizuoka Cancer Center
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: