NCT02614794

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.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
612

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jan 2016

Longer than P75 for phase_2

Geographic Reach
14 countries

172 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 20, 2015

Completed
5 days until next milestone

First Posted

Study publicly available on registry

November 25, 2015

Completed
2 months until next milestone

Study Start

First participant enrolled

January 28, 2016

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 4, 2019

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

September 28, 2020

Completed
1.9 years until next milestone

Study Completion

Last participant's last visit for all outcomes

August 11, 2022

Completed
Last Updated

August 14, 2023

Status Verified

July 1, 2023

Enrollment Period

3.6 years

First QC Date

November 20, 2015

Results QC Date

September 4, 2020

Last Update Submit

July 26, 2023

Conditions

Keywords

TucatinibCapecitabineTrastuzumabXelodaHerceptinBreast CancerARRY-380ONT-380HER2 Positive Breast CarcinomaHER2 Positive Locally Advanced Breast CancerHER-2 Positive Breast CancerHER-2 Positive Breast CarcinomaHER-2 Positive Locally Advanced Breast CancerRecurrent Breast CarcinomaStage IV Breast CancerMetastatic Breast CancerBreast CarcinomaMetastatic Malignant Neoplasm in the BrainBrain Metastases in Breast CancerAsymptomatic Brain Metastases in Breast CancerLow Symptomatic Brain Metastases in Breast CancerSeattle Genetics

Outcome Measures

Primary Outcomes (1)

  • Progression-free Survival (PFS) Per RECIST 1.1 as Determined by Blinded Independent Central Review (BICR)

    Defined as the time from the date of randomization to the date of documented disease progression.

    34.6 months

Secondary Outcomes (18)

  • PFS in Patients With Brain Metastases at Baseline Using RECIST 1.1 as Determined by BICR

    34.6 months

  • Overall Survival (OS) at Time of Primary Analysis

    35.9 months

  • Confirmed Objective Response Rate (ORR) Per RECIST 1.1 as Determined by BICR

    34.6 months

  • ORR Per RECIST 1.1 as Determined by Investigator Assessment

    34.6 months

  • PFS Per RECIST 1.1 as Determined by Investigator Assessment at Time of Primary Analysis

    34.6 months

  • +13 more secondary outcomes

Study Arms (2)

Tucatinib in combination with capecitabine & trastuzumab

EXPERIMENTAL

Tucatinib + capecitabine + trastuzumab

Drug: tucatinibDrug: capecitabineDrug: trastuzumab

Placebo in combination with capecitabine & trastuzumab

ACTIVE COMPARATOR

Placebo + capecitabine + trastuzumab

Drug: capecitabineDrug: trastuzumabDrug: placebo

Interventions

300 mg orally twice daily

Also known as: ONT-380, ARRY-380
Tucatinib in combination with capecitabine & trastuzumab

1000 mg/m2 orally twice daily on Days 1-14 of each 21-day cycle

Also known as: Xeloda
Placebo in combination with capecitabine & trastuzumabTucatinib in combination with capecitabine & trastuzumab

8 mg/kg intravenously (IV) on Day 1 of Cycle 1, followed by 6 mg/kg on Day1 of each 21-day cycle. In regions where approved, trastuzumab may be given at 600mg subcutaneously once every 3-weeks at either study initiation or crossing over from previous IV trastuzumab.

Also known as: Herceptin, Herceptin Hycleta
Placebo in combination with capecitabine & trastuzumabTucatinib in combination with capecitabine & trastuzumab

Oral dose twice daily

Placebo in combination with capecitabine & trastuzumab

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically confirmed HER2+ breast carcinoma, with HER2+ defined by in situ hybridization (ISH), immunohistochemistry (IHC), or fluorescence in situ hybridization (FISH) methodology
  • Received previous treatment with trastuzumab, pertuzumab, and T-DM1
  • Progression of unresectable locally advanced or metastatic breast cancer after last systemic therapy (as confirmed by investigator), or be intolerant of last systemic therapy
  • Have measurable or non-measurable disease assessable by RECIST 1.1
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Adequate hepatic and renal function and hematologic parameters
  • Left ventricular ejection fraction (LVEF) ≥ 50%
  • No evidence of brain metastases
  • Untreated brain metastases not needing immediate local therapy
  • Previously treated brain metastases not needing immediate local therapy
  • Brain metastases previously treated with local therapy may either be stable since treatment or may have progressed since prior local CNS therapy
  • Patients treated with CNS local therapy for newly identified lesions found on contrast brain MRI performed during screening for this study may be eligible to enroll if the following criteria are met:
  • i. Time since whole brain radiation therapy (WBRT) is ≥ 21 days prior to first dose of study treatment, time since stereotactic radiosurgery (SRS) is ≥ 7 days prior to first dose of study treatment, or time since surgical resection is ≥ 28 days.
  • ii. Other sites of disease assessable by RECIST 1.1 are present
  • Relevant records of any CNS treatment must be available to allow for classification of target and non-target lesions

You may not qualify if:

  • Previously been treated with:
  • lapatinib within 12 months of starting study treatment (except in cases where lapatinib was given for ≤ 21 days and was discontinued for reasons other than disease progression or toxicity)
  • neratinib, afatinib, or other investigational HER2/epidermal growth factor receptor (EGFR) or HER2 tyrosine kinase inhibitor (TKI) at any time previously
  • capecitabine (or other fluoropyrimidine) for metastatic disease except in cases where capecitabine was given for \< 21 days and was discontinued for reasons other than disease progression or toxicity. Patients who have received capecitabine for adjuvant or neoadjuvant treatment at least 12 months prior to starting study treatment are eligible.
  • Clinically significant cardiopulmonary disease
  • Carriers of Hepatitis B or Hepatitis C or have other known chronic liver disease
  • Positive for human immunodeficiency virus (HIV)
  • Unable for any reason to undergo MRI of the brain
  • Have used a strong CYP3A4 or CYP2C8 inhibitor within 5 half-lives of the inhibitor, or a strong CYP3A4 or CYP2C8 inducer within 5 days prior to first dose of study treatment
  • Have known dihydropyrimidine dehydrogenase deficiency (DPD)
  • Any untreated brain lesions \> 2.0 cm in size, unless approved by medical monitor
  • Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of \> 2 mg of dexamethasone (or equivalent)
  • Known or suspected leptomeningeal disease (LMD)
  • Have measurable or non-measurable disease assessable by RECIST 1.1
  • For patients who were randomized to the control arm and on the long-term follow-up period at the time of crossover screening: have progression of unresectable locally advanced or metastatic breast cancer after last systemic therapy (as confirmed by investigator), or be intolerant of last systemic therapy.
  • +34 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (176)

University of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

Location

University of South Alabama - Mitchell Cancer Institute

Mobile, Alabama, 36604, United States

Location

Cancer Treatment Centers of America - Phoenix

Goodyear, Arizona, 85338, United States

Location

Arizona Oncology Associates, PC - HAL

Phoenix, Arizona, 85016, United States

Location

City of Hope National Medical Center

Duarte, California, 91010-3000, United States

Location

TRIO - Central Regulatory Office

Los Angeles, California, 90095, United States

Location

UCLA Medical Center / David Geffen School of Medicine

Los Angeles, California, 90095, United States

Location

Torrance Memorial Physician Network - TRIO

Redondo Beach, California, 90277, United States

Location

University of California at San Francisco

San Francisco, California, 94134, United States

Location

Kaiser Permanente San Marcos Medical Offices

San Marcos, California, 92078, United States

Location

Central Coast Medical Oncology Corporation TRIO

Santa Maria, California, 93454, United States

Location

Kaiser Permanente Medical Center Northern California

Vallejo, California, 94589, United States

Location

University of Colorado Hospital / University of Colorado

Aurora, Colorado, 80045-0510, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06520, United States

Location

Lombardi Cancer Center / Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Florida Cancer Specialists - South Region

Fort Myers, Florida, 33901, United States

Location

Memorial Regional Hospital TRIO

Hollywood, Florida, 33021, United States

Location

Baptist MD Anderson Cancer Center

Jacksonville, Florida, 32207, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Mount Sinai Medical Center / Florida

Miami Beach, Florida, 33140, United States

Location

Orlando Health, Inc. TRIO

Orlando, Florida, 32806, United States

Location

Florida Cancer Specialists - North Region

St. Petersburg, Florida, 33705, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Florida Cancer Specialists - East West Palm Beach, FL (SCRI)

West Palm Beach, Florida, 33401, United States

Location

Winship Cancer Institute / Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

Cancer Treatment Centers of America

Newnan, Georgia, 30265, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Chicago

Chicago, Illinois, 60637-1470, United States

Location

Illinois Cancer Specialists / Advocate Lutheran General Hospital

Niles, Illinois, 60714, United States

Location

Carle Cancer Center

Urbana, Illinois, 61801, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Maryland Oncology Hematology, P.A.

Rockville, Maryland, 20850, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

William Beaumont Hospital

Royal Oak, Michigan, 48073, United States

Location

Virginia Piper Cancer Institute

Minneapolis, Minnesota, 55407, United States

Location

Saint Luke's Cancer Institute LLC

Kansas City, Missouri, 64113, United States

Location

Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

Location

Dartmouth-Hitchcock Medical Center/ Norris Cotton Cancer Center

Lebanon, New Hampshire, 03756, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Mount Sinai Beth Israel

New York, New York, 10003, United States

Location

New York University (NYU) Cancer Institute

New York, New York, 10016, United States

Location

Stony Brook University Cancer Center

Stony Brook, New York, 11794, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

UNC Lineberger Comprehensive Cancer Center / University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Leo W. Jenkins Cancer Services / Brody School of Medicine East Carolina University

Greenville, North Carolina, 27834, United States

Location

James Cancer Hospital / Ohio State University

Columbus, Ohio, 43210, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239-3098, United States

Location

Northwest Cancer Specialists, P.C.

Tualatin, Oregon, 97062, United States

Location

University of Pennsylvania / Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Cancer Treatment Centers of America / Eastern Regional Medical Center

Philadelphia, Pennsylvania, 19124, United States

Location

Roper St. Francis Healthcare

Charleston, South Carolina, 29414, United States

Location

Medical University of South Carolina/Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

Wellmont Cancer Institute

Kingsport, Tennessee, 37660, United States

Location

Tennessee Oncology - Nashville

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37204, United States

Location

Texas Oncology - Austin Midtown

Austin, Texas, 78705, United States

Location

Texas Oncology Methodist

Dallas, Texas, 75203, United States

Location

Texas Oncology - Denton South

Denton, Texas, 76210, United States

Location

The Center for Cancer and Blood Disorders: Fortworth

Fort Worth, Texas, 76104, United States

Location

Texas Oncology - Houston Memorial City

Houston, Texas, 77024, United States

Location

MD Anderson Cancer Center / University of Texas

Houston, Texas, 77030-4095, United States

Location

Baylor Clinic

Houston, Texas, 77030, United States

Location

Joe Arrington Cancer Research and Treatment Center

Lubbock, Texas, 79410, United States

Location

Paris Regional Medical Center / US Oncology

Paris, Texas, 75460, United States

Location

Texas Oncology - Plano East

Plano, Texas, 75075, United States

Location

Texas Oncology - San Antonio Medical Center Northeast

San Antonio, Texas, 78212, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

US Oncology Central Regulatory

The Woodlands, Texas, 77380, United States

Location

Texas Oncology - Deke Slayton Cancer Center

Webster, Texas, 77598, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Shenandoah Oncology P.C.

Winchester, Virginia, 22601, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

Seattle Cancer Care Alliance / University of Washington

Seattle, Washington, 98109-1023, United States

Location

Carbone Cancer Center / University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Austin Hospital

Heidelberg, 3084, Australia

Location

Cabrini Education and Research Precinct

Malvern, 3144, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, 3000, Australia

Location

Breast Cancer Research Centre

Nedlands, 6009, Australia

Location

Mater Hospital

North Sydney, 2060, Australia

Location

Icon Cancer Care South Brisbane

South Brisbane, 4101, Australia

Location

Mater Health Services

South Brisbane, 4101, Australia

Location

Sunshine Hospital

St Albans, 3021, Australia

Location

Westmead Hospital

Westmead, 2145, Australia

Location

LKH- Universitat Klinikum Graz

Graz, 8036, Austria

Location

Medizinische Universitat Innsbruck

Innsbruck, 6020, Austria

Location

KH d. Barmherzigen Schwestern Linz

Linz, 4010, Austria

Location

LKH Salzburg, Universitatsklinikum der PMU

Salzburg, 5020, Austria

Location

AZ Klina

Brasschaat, 2930, Belgium

Location

Cliniques Universitaires Saint Luc

Brussels, 1200, Belgium

Location

Grand Hopital de Charleroi

Charleroi, 6000, Belgium

Location

Centre Hospitalier de l'Ardenne

Libramont, 6800, Belgium

Location

CHU UCL Namur-Site de Saint Elisabeth

Namur, 5000, Belgium

Location

Tom Baker Cancer Centre

Calgary, T2N 4N2, Canada

Location

University of Alberta / Cross Cancer Institute

Edmonton, T6G 1Z2, Canada

Location

Queen Elizabeth II Health Sciences Centre

Halifax, B3H 2Y9, Canada

Location

Jewish General Hospital

Montreal, H3T 1E2, Canada

Location

Hopital du Saint-Sacrement, CHU de Quebec-Universite Laval

Québec, G1S 4L8, Canada

Location

Allan Blair Cancer Centre

Regina, S4T7T1, Canada

Location

Saskatoon Cancer Centre

Saskatoon, S7N 4H4, Canada

Location

H. Bliss Murphy Cancer Centre

St. John's, A1B 3V6, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, M4N 3M5, Canada

Location

University Health Network, Princess Margaret Hospital

Toronto, M5G 2M9, Canada

Location

British Columbia Cancer Agency - Vancouver Centre

Vancouver, V5Z 4E6, Canada

Location

Fakultni nemocnice Hradec Kralove-oddeleni klinicke hematologie

Hradec Králové, 500 05, Czechia

Location

Fakultni Nemocnice Olomouc (Fnol) - Onkologicka Klinika

Olomouc, 77520, Czechia

Location

Aalborg Universitetshospital

Aalborg, 9100, Denmark

Location

Rigs Hospiltalet

Copenhagen, DK 2100, Denmark

Location

Herlev Hospital

Herlev, 2730, Denmark

Location

Odense University Hospital

Odense C, 5000, Denmark

Location

Sygehus Lillebaelt - Vejle Sygehus

Vejle, 7100, Denmark

Location

University Hospital of Besancon

Besançon, 25030, France

Location

Clinique Victor Hugo

Le Mans, 72000, France

Location

Centre Leon Berard - Centre regional de lutte contre le cancer Rhone-Alpes

Lyon, 69373, France

Location

Institut Paoli Calmettes

Marseille, 13273, France

Location

Institute Curie - Centre de Lutte Contre Le Cancer CLCC de Paris

Paris, 75005, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Institut Jean Godinot

Reims, 51056, France

Location

Centre Eugene Marquis

Rennes, 35042, France

Location

Hopitaux Universitaires de Strasbourg

Strasbourg, 67200, France

Location

Institut Claudius Regaud

Toulouse, 31059, France

Location

CHU Tours - Hopital Bretonneau

Tours, 37044, France

Location

Charite Universitatsmedizin Berlin

Berlin, 10117, Germany

Location

Universitatsklinikum Koln

Cologne, 50937, Germany

Location

Kliniken Essen-Mitte - Evang. Huyssens-Stiftung

Essen, 45136, Germany

Location

Universitaetsklinikum Hamburg-Eppendorf (UKE) - Onkologisches Zentrum - Interdisziplinaere Klinik und Poliklinik fuer Stammzelltransplantation

Hamburg, 20246, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Universitatsklinikum Schleswig-Holstein

Kiel, 24105, Germany

Location

InVO- Institut fUr Versorgungsforschung in der onkologie GbR

Koblenz, 56068, Germany

Location

HOPE- Onkologisches Zentrum Rotkreuzklinikum

München, 80639, Germany

Location

Sana Klinikum Offenbach GmbH

Offenbach, 63069, Germany

Location

Rambam Health Corp.

Haifa, 31096, Israel

Location

Hadassah Medical Center

Jerusalem, 91120, Israel

Location

Meir Medical Center

Kfar Saba, 44281, Israel

Location

Rabin Medical Center

Petah Tikva, 49414, Israel

Location

Kaplan Medical Center

Rehovot, 76100, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

Sheba Medical Center

Tel Litwinsky, 52621, Israel

Location

Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi

Bologna, 40138, Italy

Location

Ospedale di Bolzano

Bolzano, 39100, Italy

Location

Presido Ospedaliero- Senatore Antonio Perrino

Brindisi, 72100, Italy

Location

Ospedale Ramazzini di Carpi

Carpi, 41012, Italy

Location

Ospedale Policlinico San Martino

Genova, 16132, Italy

Location

Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

IRCSS Policlinico San Matteo

Pavia, 27100, Italy

Location

Azienda Ospedaliera S. Maria di Terni

Terni, 05100, Italy

Location

A.O.U. - Ospedali Riuniti di Ancona

Torrette, 60126, Italy

Location

Hospital Cuf Descobertas R. Mario Botas Parque das Nacoes

Lisbon, 1998-018, Portugal

Location

Centro Hospitalar do Porto - Hospital Santo Antonio

Porto, 4099-001, Portugal

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, 08036, Spain

Location

Hospital San Pedro de Alcantara

Cáceres, 10002, Spain

Location

Complejo Asistencial Universitario de Leon

León, 24008, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Son Espases

Palma de Mallorca, 07010, Spain

Location

Hospital Clinico Univ De Santiago De Compostela

Santiago de Compostela, 15706, Spain

Location

Hospital Arnau De Vilanova

Valencia, 46015, Spain

Location

Hospital Clinico Universitario Lozano Blesa de Zaragoza

Zaragoza, 50009, Spain

Location

Institute of Oncology of Southern Switzerland

Bellinzona, 6500, Switzerland

Location

Colchester Hospital University NHS Foundation Trust

Colchester, C04 5JL, United Kingdom

Location

The Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

Sarah Cannon Research Institute UK

London, W1G 6AD, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Mount Vernon Hospital, UK

Northwood, HA6 2RN, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, NG5 1PD, United Kingdom

Location

Peterborough City Hospital

Peterborough, PE3 9GZ, United Kingdom

Location

Weston Park Hospital- UK

Sheffield, S10 2SJ, United Kingdom

Location

The Royal Marsden Hospital (Surrey)

Sutton, SM2 5PT, United Kingdom

Location

Royal Cornwall Hospitals NHS Trust

Truro, TR1 3LQ, United Kingdom

Location

Related Publications (6)

  • Dai L, Gao T, Guo R, Chen Y, Wang J, Zhou S, Tang Y, Chen D, Huang S. Efficacy and safety of pyrotinib-based regimens in HER2 positive metastatic breast cancer: A retrospective real-world data study. Neoplasia. 2024 Oct;56:101029. doi: 10.1016/j.neo.2024.101029. Epub 2024 Jul 17.

  • Lin NU, Murthy RK, Abramson V, Anders C, Bachelot T, Bedard PL, Borges V, Cameron D, Carey LA, Chien AJ, Curigliano G, DiGiovanna MP, Gelmon K, Hortobagyi G, Hurvitz SA, Krop I, Loi S, Loibl S, Mueller V, Oliveira M, Paplomata E, Pegram M, Slamon D, Zelnak A, Ramos J, Feng W, Winer E. Tucatinib vs Placebo, Both in Combination With Trastuzumab and Capecitabine, for Previously Treated ERBB2 (HER2)-Positive Metastatic Breast Cancer in Patients With Brain Metastases: Updated Exploratory Analysis of the HER2CLIMB Randomized Clinical Trial. JAMA Oncol. 2023 Feb 1;9(2):197-205. doi: 10.1001/jamaoncol.2022.5610.

  • Mueller V, Wardley A, Paplomata E, Hamilton E, Zelnak A, Fehrenbacher L, Jakobsen E, Curtit E, Boyle F, Harder Brix E, Brenner A, Crouzet L, Ferrario C, Munoz-Mateu M, Arkenau HT, Iqbal N, Aithal S, Block M, Cold S, Cancel M, Hahn O, Poosarla T, Stringer-Reasor E, Colleoni M, Cameron D, Curigliano G, Siadak M, DeBusk K, Ramos J, Feng W, Gelmon K. Preservation of quality of life in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer treated with tucatinib or placebo when added to trastuzumab and capecitabine (HER2CLIMB trial). Eur J Cancer. 2021 Aug;153:223-233. doi: 10.1016/j.ejca.2021.05.025. Epub 2021 Jun 29.

  • Lin NU, Borges V, Anders C, Murthy RK, Paplomata E, Hamilton E, Hurvitz S, Loi S, Okines A, Abramson V, Bedard PL, Oliveira M, Mueller V, Zelnak A, DiGiovanna MP, Bachelot T, Chien AJ, O'Regan R, Wardley A, Conlin A, Cameron D, Carey L, Curigliano G, Gelmon K, Loibl S, Mayor J, McGoldrick S, An X, Winer EP. Intracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial. J Clin Oncol. 2020 Aug 10;38(23):2610-2619. doi: 10.1200/JCO.20.00775. Epub 2020 May 29.

  • Murthy RK, Loi S, Okines A, Paplomata E, Hamilton E, Hurvitz SA, Lin NU, Borges V, Abramson V, Anders C, Bedard PL, Oliveira M, Jakobsen E, Bachelot T, Shachar SS, Muller V, Braga S, Duhoux FP, Greil R, Cameron D, Carey LA, Curigliano G, Gelmon K, Hortobagyi G, Krop I, Loibl S, Pegram M, Slamon D, Palanca-Wessels MC, Walker L, Feng W, Winer EP. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. N Engl J Med. 2020 Feb 13;382(7):597-609. doi: 10.1056/NEJMoa1914609. Epub 2019 Dec 11.

  • Murthy R, Borges VF, Conlin A, Chaves J, Chamberlain M, Gray T, Vo A, Hamilton E. Tucatinib with capecitabine and trastuzumab in advanced HER2-positive metastatic breast cancer with and without brain metastases: a non-randomised, open-label, phase 1b study. Lancet Oncol. 2018 Jul;19(7):880-888. doi: 10.1016/S1470-2045(18)30256-0. Epub 2018 May 24.

MeSH Terms

Conditions

Breast NeoplasmsBrain Neoplasms

Interventions

tucatinibCapecitabineTrastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesCentral Nervous System NeoplasmsNervous System NeoplasmsBrain DiseasesCentral Nervous System DiseasesNervous System Diseases

Intervention Hierarchy (Ancestors)

DeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsFluorouracilUracilPyrimidinonesDeoxyribonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Results Point of Contact

Title
Chief Medical Officer
Organization
Seattle Genetics, Inc.

Study Officials

  • Jorge Ramos, DO

    Seagen Inc.

    STUDY DIRECTOR
  • Corinna Palanca-Wessels, MD, PhD

    Seagen Inc.

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
Masking applied only during the Double-blind phase of the trial. The Unblinded Phase is open-label.
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR
Expanded Access
Yes

Study Record Dates

First Submitted

November 20, 2015

First Posted

November 25, 2015

Study Start

January 28, 2016

Primary Completion

September 4, 2019

Study Completion

August 11, 2022

Last Updated

August 14, 2023

Results First Posted

September 28, 2020

Record last verified: 2023-07

Locations