A Study of DS-8201a in Metastatic Breast Cancer Previously Treated With Trastuzumab Emtansine (T-DM1)
- Registration Number
- NCT03248492
- Lead Sponsor
- Daiichi Sankyo
- Brief Summary
Some human epidermal growth factor receptor 2 (HER-2) breast cancer patients do not respond or become resistant to current treatment. DS-8201a is a new experimental product that is a combination of an antibody and a drug. It has not yet been approved for use. DS-8201a may slow down tumor growth. This might improve outcomes for these patients.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 253
-
Men or women the age of majority in their country
-
Has pathologically documented breast cancer that:
- is unresectable or metastatic
- has HER2 positive expression confirmed per protocol
-
Has an adequate tumor sample
-
Has at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
-
Has protocol-defined adequate cardiac, renal and hepatic function
-
Agrees to follow protocol-defined method(s) of contraception
-
Has a medical history of myocardial infarction, symptomatic congestive heart failure (CHF) (NYHA classes II-IV), unstable angina or serious cardiac arrhythmia
-
Has a corrected QT interval (QTc) prolongation to > 450 millisecond (ms) in males and > 470 ms in females
-
Has a medical history of clinically significant lung disease
-
Is suspected to have certain other protocol-defined diseases based on imaging at screening period
-
Has history of any disease, metastatic condition, drug/medication use or other condition that might, per protocol or in the opinion of the investigator, compromise:
- safety or well-being of the participant or offspring
- safety of study staff
- analysis of results
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description DS-8201a Low Dose DS-8201a T-DM1 resistant/refractory (R/R) patients in the low dose treatment group DS-8201a Medium Dose DS-8201a T-DM1 resistant/refractory (R/R) patients in the medium dose treatment group DS-8201a High Dose DS-8201a T-DM1 resistant/refractory (R/R) patients in the high dose treatment group Exploratory Arm DS-8201a In Part 2b- Continuation Stage, about 10 T-DM1 Intolerant patients will receive the DS-8201a recommended dose (RD) as an exploratory arm
- Primary Outcome Measures
Name Time Method Objective Response Rate as Confirmed by Independent Central Review Following Intravenous Administration of 5.4 mg/kg DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) at least 6 months after last participant enrolled received first dose up to 19 months (data cut off) The number of participants with objective response was assessed every six weeks from Cycle 1 Day 1 through discontinuation of treatment, by independent central imaging facility review based on RECIST version 1.1.
- Secondary Outcome Measures
Name Time Method Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) at least 6 months after last participant enrolled received first dose up to 19 months (data cut off) Best overall tumor response was defined as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) by the investigator based on RECIST v1.1. Participants who were non-evaluable (NE) are also reported.
Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) Baseline up to Week 6, 12, 18, 24, 30, 36 post dose Best percent change in sum of diameters of measurable tumors was based on RECIST 1.1. The best percent change was defined as the percent change in the smallest sum of diameters from all post-baseline tumor assessments, taking as reference the baseline sum of diameters.
Objective Response Rate as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) at least 6 months after last participant enrolled received first dose up to 19 months (data cut off) The number of participants with objective response is assessed every six weeks from Cycle 1 Day 1 through discontinuation of treatment. Investigator-assessed objective response rate (ORR) was defined as the proportion of participants who achieved a best overall response of complete response or partial response based on local radiologists/investigators' tumor assessments.
Disease Control Rate and Clinical Benefit Rate as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) at least 6 months after last participant enrolled received first dose up to 19 months (data cut off) Number of participants with controlled disease and who received clinical benefit from treatment as assessed by independent central review. DCR was defined as the proportion of participants who achieved a best overall response of complete response, partial response, or stable disease. CBR was defined as the proportion of participants who achieved a best overall response of complete response or partial response or more than 6 months of stable disease.
Duration of Response (Complete Response or Partial Response) as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) at least 6 months after last participant enrolled received first dose up to 19 months (data cut off) The estimated duration of confirmed response (complete response \[CR\] or partial response \[PR\]) was assessed by independent central review. Duration of response was defined as the time interval between the date of first documentation of objective response (CR or PR) and the date of the first objective documentation of disease progression or death due to any cause.
Progression-Free Survival Estimate As Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) at least 6 months after last participant enrolled received first dose up to 19 months (data cut off) The point estimate of progression-free survival (PFS) is reported. PFS was defined as the time interval between the date of randomization/registration and the first documentation of disease progression or death due to any cause.
Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) Day 0 to Day 47 post last dose TEAEs were assessed by severity and seriousness according to unique criteria. Severity described the intensity of an event and was graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03, where Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL); Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL; Grade 4: Life-threatening consequences; urgent intervention indicated; and Grade 5: Death related to AE. Serious TEAEs were defined as any untoward medical occurrence that at any dose results in death, is life threatening, requires inpatient hospitalization, or causes prolongation of existing hospitalization.
Trial Locations
- Locations (99)
The Regents of the University of California
🇺🇸Los Angeles, California, United States
Virginia Cancer Specialists, PC
🇺🇸Fairfax, Virginia, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Texas Oncology - Memorial City
🇺🇸Houston, Texas, United States
Miami Cancer Institute at Baptist Health, Inc.
🇺🇸Miami, Florida, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
The Methodist Hospital Research Institute
🇺🇸Houston, Texas, United States
CRLCC Eugene Marquis
🇫🇷Rennes, France
Grand Hôpital de Charleroi
🇧🇪Charleroi, Belgium
AZ Sint-Maarten
🇧🇪Mechelen, Belgium
Institut Sainte Catherine
🇫🇷Avignon, France
Piedmont Cancer Institute
🇺🇸Atlanta, Georgia, United States
UZ Leuven
🇧🇪Leuven, Belgium
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Centre Catherine de Sienne
🇫🇷Nantes, France
Ospedale San Raffaele
🇮🇹Milano, Italy
Innovative Clinical Research Institute, LLC
🇺🇸Whittier, California, United States
Aichi Cancer Center Hospital
🇯🇵Aichi, Japan
University of Calgary
🇨🇦Calgary, Alberta, Canada
Sylvester Comprehensive Cancer Center - Deerfield Beach
🇺🇸Boca Raton, Florida, United States
UPMC Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Imeldaziekenhuis
🇧🇪Bonheiden, Belgium
Providence Regional Medical Center - Everett
🇺🇸Everett, Washington, United States
CHU Besançon - Hôpital Jean Minjoz
🇫🇷Besançon, France
Hôpital d'Instruction des Armees Begin
🇫🇷Saint-Mandé, France
Centre Paul Strauss
🇫🇷Strasbourg, France
Texas Oncology, P.A. - Longview
🇺🇸Tyler, Texas, United States
Hôpital Nord - CHU Marseille
🇫🇷Marseille, France
Centre Hospitalier Lyon Sud
🇫🇷Pierre-Bénite, France
NHO Kyushu Cancer Center
🇯🇵Fukuoka, Japan
Toranomon Hospital
🇯🇵Minato-Ku, Tokyo-To, Japan
Kyungpook National University Chilgok Hospital
🇰🇷Daegu, Korea, Republic of
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, Italy
National Cancer Center Hospital
🇯🇵Tokyo, Japan
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Azienda Socio Sanitaria Territoriale di Monza (Presidio San Gerardo)
🇮🇹Monza, Italy
Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona
🇮🇹Torrette, Italy
St. Luke's International Hospital
🇯🇵Tokyo, Japan
University of California San Francisco
🇺🇸San Francisco, California, United States
Clinique Victor Hugo - Centre Jean Bernard
🇫🇷Le Mans, France
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
CH de la Rochelle - Hopital St Louis
🇫🇷La Rochelle, France
Arizona Oncology Associates
🇺🇸Tucson, Arizona, United States
Sharp Clinical Oncology Research
🇺🇸San Diego, California, United States
Sansum Clinic
🇺🇸Santa Barbara, California, United States
Specialist Global Research
🇺🇸Hialeah, Florida, United States
Aultman Hospital Cancer Center
🇺🇸Canton, Ohio, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
St Francis Hospital
🇺🇸Greenville, South Carolina, United States
Accurate Clinical Research
🇺🇸Baytown, Texas, United States
CHU Sart Tilman
🇧🇪Liège, Belgium
Institut Régional du Cancer de Montpellier
🇫🇷Montpellier, France
Institut Gustave Roussy
🇫🇷Villejuif, France
NHO Shikoku Cancer Center
🇯🇵Matsuyama, Ehime-Ken, Japan
IEO Istituto Europeo di Oncologia
🇮🇹Milano, Italy
Ospedale degli Infermi
🇮🇹Rimini, Italy
National Cancer Center Hospital East
🇯🇵Chiba, Japan
Kanagawa Cancer Center
🇯🇵Kanagawa, Japan
Hakuaikai Sagara Hospital
🇯🇵Kagoshima, Japan
Kindai University Hospital
🇯🇵Osaka, Japan
Cancer Institute Hospital of JFCR
🇯🇵Tokyo, Japan
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Hospital Infanta Cristina
🇪🇸Badajoz, Spain
Severance Hospital, Yonsei University
🇰🇷Seoul, Korea, Republic of
MD Anderson Cancer Centre
🇪🇸Madrid, Spain
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Universitari Quiron Dexeus
🇪🇸Barcelona, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Instituto Valenciano de Oncologia IVO
🇪🇸Valencia, Spain
Western General Hospital
🇬🇧Edinburgh, Lothian Region, United Kingdom
University College London Hospitals
🇬🇧London, Greater London, United Kingdom
North Shore Hematology Oncology Associates PC DBA NY Cancer and Blood Specialists
🇺🇸East Setauket, New York, United States
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Centre Georges François Leclerc
🇫🇷Dijon, France
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
CHU Bordeaux - Hôpital Saint André
🇫🇷Gironde, France
Texas Oncology, P.A.
🇺🇸Dallas, Texas, United States
ICO l´Hospitalet - Hospital Duran i Reynals
🇪🇸Barcelona, Spain
Hôpital Saint-Louis - Paris
🇫🇷Paris, France
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Hospital Quiron Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Clinico Universitario Virgen de la Victoria
🇪🇸Málaga, Spain
Alaska Urological Institute dba Alaska Clinical Research Center
🇺🇸Anchorage, Alaska, United States
Norton Healthcare
🇺🇸Louisville, Kentucky, United States
University of Louisville Research Foundation
🇺🇸Louisville, Kentucky, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Royal Surrey County Hospital
🇬🇧Guildford, Surrey, United Kingdom
Queen Mary University of London
🇬🇧London, Greater London, United Kingdom
Nottingham University Hospitals City Campus
🇬🇧Nottingham, Nottinghamshire, United Kingdom
National Cancer Center
🇰🇷Goyang-si, Korea, Republic of
Derriford Hospital
🇬🇧Plymouth, Devon, United Kingdom
The University of Texas Health Science Center at Tyler
🇺🇸Tyler, Texas, United States
Straub Medical Center
🇺🇸Honolulu, Hawaii, United States
University of Hawaii
🇺🇸Honolulu, Hawaii, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States