A Study of Tucatinib vs. Placebo in Combination With Capecitabine & Trastuzumab in Patients With Advanced HER2+ Breast Cancer
- Conditions
- HER2 Positive Breast Cancer
- Interventions
- Registration Number
- NCT02614794
- Lead Sponsor
- Seagen Inc.
- Brief Summary
This study is being done to see if tucatinib works better than placebo to help patients who have a specific type of breast cancer called HER2 positive breast carcinoma. The breast cancer in this study is either metastatic (spread into other parts of the body) or cannot be removed completely with surgery. All patients in the study will get capecitabine and trastuzumab, two drugs that are often used to treat this cancer.
There are two parts to this study. The first part of the study is already complete. Patients were randomly assigned to get either tucatinib or placebo (a pill with no medicine). Since this part was "blinded," neither patients nor their doctors knew whether a patient got tucatinib or placebo.
The second part of the study is called the Unblinded Phase. In this part of the study, participants and their doctors know which drugs are being given. Participants who used to get or are currently getting placebo may be able to start taking tucatinib instead.
Each treatment cycle lasts 21 days. Patients will swallow tucatinib pills two times every day. They will swallow capecitabine pills two times a day during the first two weeks of each cycle. Patients will get trastuzumab injections from the study site staff on the first day of every cycle.
- Detailed Description
This is a randomized, international, multi-center study in patients with progressive unresectable locally advanced or metastatic HER2+ breast cancer who have had prior treatment with trastuzumab, pertuzumab and T-DM1. There are two phases to this trial: the Double-blind Phase and the Unblinded Phase. In the Double-blind phase, participants were randomized in a 2:1 ratio to receive tucatinib or placebo in combination with capecitabine and trastuzumab. In the Unblinded Phase, patients on placebo may be offered tucatinib.
Stratification factors include presence or history of treated or untreated brain metastases or brain lesions of equivocal significance (yes/no), Eastern Cooperative Oncology Group (ECOG) Performance Status (0 vs. 1), and region of world (US vs. Canada vs. Rest of World).
Safety assessments will be performed at a minimum of once every three weeks throughout study treatment and 30 days after the last dose of study drugs. Laboratory assessments will be performed locally at sites. Left ventricular ejection fraction will be assessed by MUGA or ECHO at screening and once every 12 weeks thereafter.
For the blinded phase, contrast brain MRI was performed at baseline. Efficacy assessments (CT of chest, abdomen and pelvis at a minimum) utilized RECIST 1.1 and included patients with evaluable tumors defined as measurable target lesions and non-measurable non-target lesions. RECIST assessment was performed at baseline, every 6 weeks for the first 24 weeks, and then every 9 weeks thereafter. Repeat MRI of the brain was required on this same schedule only in those patients with brain metastases identified at baseline. All treatment decisions were made based upon investigator assessment. All patients underwent a repeat MRI of the brain within 30 days of the end of treatment unless previously performed at time of disease progression.
For the unblinded phase, RECIST assessments will be performed per standard clinical practice as determined by investigator with a maximum interval of 12 weeks.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 612
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo in combination with capecitabine & trastuzumab placebo Placebo + capecitabine + trastuzumab Tucatinib in combination with capecitabine & trastuzumab capecitabine Tucatinib + capecitabine + trastuzumab Tucatinib in combination with capecitabine & trastuzumab tucatinib Tucatinib + capecitabine + trastuzumab Tucatinib in combination with capecitabine & trastuzumab trastuzumab Tucatinib + capecitabine + trastuzumab Placebo in combination with capecitabine & trastuzumab trastuzumab Placebo + capecitabine + trastuzumab Placebo in combination with capecitabine & trastuzumab capecitabine Placebo + capecitabine + trastuzumab
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) Per RECIST 1.1 as Determined by Blinded Independent Central Review (BICR) 34.6 months Defined as the time from the date of randomization to the date of documented disease progression.
- Secondary Outcome Measures
Name Time Method Incidence of Adverse Events (AEs) at Time of Primary Analysis 36.1 months As determined by assessment of AEs, clinical laboratory tests, and vital signs measurements. AEs were classified by system organ class (SOC) and preferred term using the Medical Dictionary for Regulatory Activities (MedDRA) Version 22.0 or higher; AE severities were classified using Version 4.03 of the (Common Terminology Criteria for Adverse Events) CTCAE criteria.
Frequency of Dose Modifications 35.1 months Incidence of Health Resources Utilization 36.1 months Cumulative incidence of health resource utilization, including length of stay, hospitalizations, and ER visits using the EQ-5D-5L questionnaire.
Pharmacokinetic Measure: Ctrough of Tucatinib 3.5 months Individual plasma tucatinib concentrations at each sampling time
Overall Survival (OS) at Time of Final Analysis Up to 60.1 months Defined as time from randomization to death from any cause
PFS Per RECIST 1.1 as Determined by Investigator Assessment at Time of Final Analysis Up to 58.0 months Defined as the time from the date of randomization to the date of documented disease progression
PFS Per RECIST 1.1 as Determined by Investigator Assessment at Time of Primary Analysis 34.6 months Defined as the time from the date of randomization to the date of documented disease progression
Duration of Response (DOR) Per RECIST 1.1 as Determined by BICR 24.6 months Defined as the time from the first objective response to documented disease progression or death from any cause, whichever occurred first.
Incidence of Adverse Events (AEs) at Time of Final Analysis Up to 60.1 months As determined by assessment of AEs, clinical laboratory tests, and vital signs measurements. AEs were classified by system organ class (SOC) and preferred term using the Medical Dictionary for Regulatory Activities (MedDRA) Version 22.0 or higher; AE severities were classified using Version 4.03 of the (Common Terminology Criteria for Adverse Events) CTCAE criteria.
Frequency of Dose Modifications at Time of Final Analysis Up to 60.1 months Confirmed Objective Response Rate (ORR) Per RECIST 1.1 as Determined by BICR 34.6 months Defined as achieving a best overall response of confirmed complete response (CR) or confirmed partial response (PR).
PFS in Patients With Brain Metastases at Baseline Using RECIST 1.1 as Determined by BICR 34.6 months Defined as the time from the date of randomization to the date of documented disease progression.
Overall Survival (OS) at Time of Primary Analysis 35.9 months Defined as time from randomization to death from any cause
DOR Per RECIST 1.1 as Determined by Investigator Assessment 33.2 months Defined as the time from the first objective response to documented disease progression or death from any cause, whichever occurred first.
ORR Per RECIST 1.1 as Determined by Investigator Assessment 34.6 months Defined as achieving a best overall response of confirmed CR or confirmed PR.
Clinical Benefit Rate (CBR) as Determined by BICR Per RECIST 1.1 34.6 months Clinical benefit was defined as achieving stable disease (SD) or non-complete response (CR)/non-progressive disease (PD) for at least 6 months or a best overall response of confirmed CR or confirmed partial response (PR).
CBR Per RECIST 1.1 as Determined by Investigator Assessment 34.6 months Clinical benefit was defined as achieving stable disease (SD) or non-CR/non-PD for at least 6 months or a best overall response of confirmed CR or confirmed PR.
Pharmacokinetic Measure: ONT-993 3.5 months Individual plasma primary metabolite concentrations at each sampling time
Trial Locations
- Locations (176)
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
University of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
Paris Regional Medical Center / US Oncology
🇺🇸Paris, Texas, United States
Cancer Treatment Centers of America / Eastern Regional Medical Center
🇺🇸Philadelphia, Pennsylvania, United States
Texas Oncology Methodist
🇺🇸Dallas, Texas, United States
James Cancer Hospital / Ohio State University
🇺🇸Columbus, Ohio, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Texas Oncology - Houston Memorial City
🇺🇸Houston, Texas, United States
MD Anderson Cancer Center / University of Texas
🇺🇸Houston, Texas, United States
Baylor Clinic
🇺🇸Houston, Texas, United States
Swedish Cancer Institute
🇺🇸Seattle, Washington, United States
Memorial Regional Hospital TRIO
🇺🇸Hollywood, Florida, United States
Shenandoah Oncology P.C.
🇺🇸Winchester, Virginia, United States
Maryland Oncology Hematology, P.A.
🇺🇸Rockville, Maryland, United States
Allan Blair Cancer Centre
🇨🇦Regina, Canada
Virginia Piper Cancer Institute
🇺🇸Minneapolis, Minnesota, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Texas Oncology - San Antonio Medical Center Northeast
🇺🇸San Antonio, Texas, United States
Medizinische Universitat Innsbruck
🇦🇹Innsbruck, Austria
Wellmont Cancer Institute
🇺🇸Kingsport, Tennessee, United States
LKH- Universitat Klinikum Graz
🇦🇹Graz, Austria
Augusta University
🇺🇸Augusta, Georgia, United States
Dartmouth-Hitchcock Medical Center/ Norris Cotton Cancer Center
🇺🇸Lebanon, New Hampshire, United States
University of Miami
🇺🇸Miami, Florida, United States
City of Hope National Medical Center
🇺🇸Duarte, California, United States
Lombardi Cancer Center / Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
CHU UCL Namur-Site de Saint Elisabeth
🇧🇪Namur, Belgium
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Cancer Treatment Centers of America - Phoenix
🇺🇸Goodyear, Arizona, United States
Meir Medical Center
🇮🇱Kfar Saba, Israel
Rabin Medical Center
🇮🇱Petach Tikva, Israel
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Arizona Oncology Associates, PC - HAL
🇺🇸Phoenix, Arizona, United States
University of California at San Francisco
🇺🇸San Francisco, California, United States
Tennessee Oncology - Nashville
🇺🇸Nashville, Tennessee, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Rigs Hospiltalet
🇩🇰Copenhagen, Denmark
Istituto Europeo di Oncologia
🇮🇹Milano, Italy
Azienda Ospedaliera S. Maria di Terni
🇮🇹Terni, Italy
A.O.U. - Ospedali Riuniti di Ancona
🇮🇹Torrette, Italy
Ospedale Ramazzini di Carpi
🇮🇹Carpi, Italy
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Aalborg Universitetshospital
🇩🇰Aalborg, Denmark
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
HOPE- Onkologisches Zentrum Rotkreuzklinikum
🇩🇪Munchen, Germany
Saskatoon Cancer Centre
🇨🇦Saskatoon, Canada
H. Bliss Murphy Cancer Centre
🇨🇦St John's, Canada
Fakultni nemocnice Hradec Kralove-oddeleni klinicke hematologie
🇨🇿Hradec Kralove, Czechia
Clinique Victor Hugo
🇫🇷Le Mans, France
Rambam Health Corp.
🇮🇱Haifa, Israel
Kaplan Medical Center
🇮🇱Rehovot, Israel
Herlev Hospital
🇩🇰Herlev, Denmark
University Hospital of Besancon
🇫🇷Besancon cedex, France
Centre Leon Berard - Centre regional de lutte contre le cancer Rhone-Alpes
🇫🇷Lyon, France
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Charite Universitatsmedizin Berlin
🇩🇪Berlin, Germany
Kliniken Essen-Mitte - Evang. Huyssens-Stiftung
🇩🇪Essen, Germany
Universitatsklinikum Schleswig-Holstein
🇩🇪Kiel, Germany
Sheba Medical Center
🇮🇱Tel Hashomer, Israel
Ospedale Policlinico San Martino
🇮🇹Genova, Italy
Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi
🇮🇹Bologna, Italy
InVO- Institut fUr Versorgungsforschung in der onkologie GbR
🇩🇪Koblenz, Germany
Presido Ospedaliero- Senatore Antonio Perrino
🇮🇹Brindisi, Italy
Hadassah Medical Center
🇮🇱Jerusalem, Israel
Hospital Cuf Descobertas R. Mario Botas Parque das Nacoes
🇵🇹Lisboa, Portugal
Universitatsklinikum Koln
🇩🇪Köln, Germany
Ospedale di Bolzano
🇮🇹Bolzano, Italy
Centro Hospitalar do Porto - Hospital Santo Antonio
🇵🇹Porto, Portugal
Colchester Hospital University NHS Foundation Trust
🇬🇧Colchester, United Kingdom
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Clinic i Provincial de Barcelona
🇪🇸Barcelona, Spain
IRCSS Policlinico San Matteo
🇮🇹Pavia, Italy
Hospital San Pedro de Alcantara
🇪🇸Caceres, Spain
Institute of Oncology of Southern Switzerland
🇨🇭Bellinzona, Switzerland
Hospital Son Espases
🇪🇸Palma de Mallorca, Spain
Hospital Clinico Universitario Lozano Blesa de Zaragoza
🇪🇸Zaragoza, Spain
Institut Paoli Calmettes
🇫🇷Marseille, France
Centre Hospitalier Lyon Sud
🇫🇷Pierre Bénite Cedex, France
Institut Jean Godinot
🇫🇷REIMS Cedex, France
Centre Eugene Marquis
🇫🇷Rennes Cedex, France
Hopitaux Universitaires de Strasbourg
🇫🇷Strasbourg, France
Institut Claudius Regaud
🇫🇷Toulouse Cedex 9, France
CHU Tours - Hopital Bretonneau
🇫🇷TOURS Cedex 09, France
The Royal Marsden Hospital
🇬🇧London, United Kingdom
Sarah Cannon Research Institute UK
🇬🇧London, United Kingdom
Peterborough City Hospital
🇬🇧Peterborough, United Kingdom
Weston Park Hospital- UK
🇬🇧Sheffield, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
The Royal Marsden Hospital (Surrey)
🇬🇧Sutton, United Kingdom
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Canada
University Health Network, Princess Margaret Hospital
🇨🇦Toronto, Canada
British Columbia Cancer Agency - Vancouver Centre
🇨🇦Vancouver, Canada
Universitaetsklinikum Hamburg-Eppendorf (UKE) - Onkologisches Zentrum - Interdisziplinaere Klinik und Poliklinik fuer Stammzelltransplantation
🇩🇪Hamburg, Germany
Sana Klinikum Offenbach GmbH
🇩🇪Offenbach am Main, Germany
Complejo Asistencial Universitario de Leon
🇪🇸Leon, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Hospital Arnau De Vilanova
🇪🇸Valencia, Spain
Hospital Clinico Univ De Santiago De Compostela
🇪🇸Santiago de Compostela, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Cancer Treatment Centers of America
🇺🇸Newnan, Georgia, United States
University of Colorado Hospital / University of Colorado
🇺🇸Aurora, Colorado, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
H. Lee Moffitt Cancer Center and Research Institute
🇺🇸Tampa, Florida, United States
Orlando Health, Inc. TRIO
🇺🇸Orlando, Florida, United States
Nebraska Cancer Specialists
🇺🇸Omaha, Nebraska, United States
University of South Alabama - Mitchell Cancer Institute
🇺🇸Mobile, Alabama, United States
Torrance Memorial Physician Network - TRIO
🇺🇸Redondo Beach, California, United States
UCLA Medical Center / David Geffen School of Medicine
🇺🇸Los Angeles, California, United States
TRIO - Central Regulatory Office
🇺🇸Los Angeles, California, United States
Florida Cancer Specialists - South Region
🇺🇸Fort Myers, Florida, United States
Kaiser Permanente San Marcos Medical Offices
🇺🇸San Marcos, California, United States
Kaiser Permanente Medical Center Northern California
🇺🇸Vallejo, California, United States
Central Coast Medical Oncology Corporation TRIO
🇺🇸Santa Maria, California, United States
Baptist MD Anderson Cancer Center
🇺🇸Jacksonville, Florida, United States
Mount Sinai Medical Center / Florida
🇺🇸Miami Beach, Florida, United States
Florida Cancer Specialists - North Region
🇺🇸Saint Petersburg, Florida, United States
Florida Cancer Specialists - East West Palm Beach, FL (SCRI)
🇺🇸West Palm Beach, Florida, United States
Winship Cancer Institute / Emory University School of Medicine
🇺🇸Atlanta, Georgia, United States
Northside Hospital
🇺🇸Atlanta, Georgia, United States
University of Maryland
🇺🇸Baltimore, Maryland, United States
Illinois Cancer Specialists / Advocate Lutheran General Hospital
🇺🇸Niles, Illinois, United States
William Beaumont Hospital
🇺🇸Royal Oak, Michigan, United States
Mount Sinai Beth Israel
🇺🇸New York, New York, United States
Stony Brook University Cancer Center
🇺🇸Stony Brook, New York, United States
New York University (NYU) Cancer Institute
🇺🇸New York, New York, United States
Leo W. Jenkins Cancer Services / Brody School of Medicine East Carolina University
🇺🇸Greenville, North Carolina, United States
Northwest Cancer Specialists, P.C.
🇺🇸Tualatin, Oregon, United States
University of Pennsylvania / Perelman Center for Advanced Medicine
🇺🇸Philadelphia, Pennsylvania, United States
Texas Oncology - Austin Midtown
🇺🇸Austin, Texas, United States
Texas Oncology - Denton South
🇺🇸Denton, Texas, United States
The Center for Cancer and Blood Disorders: Fortworth
🇺🇸Fort Worth, Texas, United States
Joe Arrington Cancer Research and Treatment Center
🇺🇸Lubbock, Texas, United States
Texas Oncology - Plano East
🇺🇸Plano, Texas, United States
US Oncology Central Regulatory
🇺🇸The Woodlands, Texas, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Virginia Cancer Specialists, PC
🇺🇸Fairfax, Virginia, United States
Texas Oncology - Deke Slayton Cancer Center
🇺🇸Webster, Texas, United States
Westmead Hospital
🇦🇺Westmead, Australia
Seattle Cancer Care Alliance / University of Washington
🇺🇸Seattle, Washington, United States
Austin Hospital
🇦🇺Heidelberg, Australia
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Australia
Cabrini Education and Research Precinct
🇦🇺Malvern, Australia
Carbone Cancer Center / University of Wisconsin
🇺🇸Madison, Wisconsin, United States
Mater Hospital
🇦🇺North Sydney, Australia
Breast Cancer Research Centre
🇦🇺Nedlands, Australia
Mater Health Services
🇦🇺South Brisbane, Australia
Icon Cancer Care South Brisbane
🇦🇺South Brisbane, Australia
Sunshine Hospital
🇦🇺St Albans, Australia
KH d. Barmherzigen Schwestern Linz
🇦🇹Linz, Austria
LKH Salzburg, Universitatsklinikum der PMU
🇦🇹Salzburg, Austria
Grand Hopital de Charleroi
🇧🇪Charleroi, Belgium
Cliniques Universitaires Saint Luc
🇧🇪Brussels, Belgium
AZ Klina
🇧🇪Brasschaat, Belgium
Centre Hospitalier de l'Ardenne
🇧🇪Libramont, Belgium
Tom Baker Cancer Centre
🇨🇦Calgary, Canada
University of Alberta / Cross Cancer Institute
🇨🇦Edmonton, Canada
Hopital du Saint-Sacrement, CHU de Quebec-Universite Laval
🇨🇦Quebec, Canada
Jewish General Hospital
🇨🇦Montreal, Canada
Mount Vernon Hospital, UK
🇬🇧Northwood, United Kingdom
Odense University Hospital
🇩🇰Odense C, Denmark
Sygehus Lillebaelt - Vejle Sygehus
🇩🇰Vejle, Denmark
Fakultni Nemocnice Olomouc (Fnol) - Onkologicka Klinika
🇨🇿Olomouc, Czechia
Institute Curie - Centre de Lutte Contre Le Cancer CLCC de Paris
🇫🇷Paris, France
Nottingham University Hospitals NHS Trust
🇬🇧Nottingham, United Kingdom
Saint Luke's Cancer Institute LLC
🇺🇸Kansas City, Missouri, United States
UNC Lineberger Comprehensive Cancer Center / University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
Roper St. Francis Healthcare
🇺🇸Charleston, South Carolina, United States
Medical University of South Carolina/Hollings Cancer Center
🇺🇸Charleston, South Carolina, United States
Royal Cornwall Hospitals NHS Trust
🇬🇧Truro, United Kingdom
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Queen Elizabeth II Health Sciences Centre
🇨🇦Halifax, Canada