AzTrials
AzTrials

HER2 Positive Breast CancerPhase 2HER2CLIMBNCT02614794

A Study of Tucatinib vs. Placebo in Combination With Capecitabine & Trastuzumab in Patients With Advanced HER2+ Breast Cancer

A Phase 2 study testing tucatinib, capecitabine and trastuzumab in people with HER2 Positive Breast Cancer, run by Seagen Inc. at 176 sites in 15 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HER2 Positive Breast Cancer
What is being tested?
tucatinib, capecitabine and trastuzumab
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
612 participants
Where
176 sitesin 15 countries
Study dates
28 Jan 2016to 11 Aug 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Double-blind Phase Inclusion Criteria

  • 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%
  • CNS Inclusion - Based on screening brain magnetic resonance imaging (MRI), patients must have one of the following:
  1. No evidence of brain metastases
  2. Untreated brain metastases not needing immediate local therapy
  3. Previously treated brain metastases not needing immediate local therapy
  4. Brain metastases previously treated with local therapy may either be stable since treatment or may have progressed since prior local CNS therapy
  5. 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:
  6. 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
  7. Relevant records of any CNS treatment must be available to allow for classification of target and non-target lesions

Double-blind Phase Exclusion Criteria

  • Previously been treated with:
  1. 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)
  2. neratinib, afatinib, or other investigational HER2/epidermal growth factor receptor (EGFR) or HER2 tyrosine kinase inhibitor (TKI) at any time previously
  3. 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)
  • CNS Exclusion - Based on screening brain MRI, patients must not have any of the following:
  1. Any untreated brain lesions > 2.0 cm in size, unless approved by medical monitor
  2. Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of > 2 mg of dexamethasone (or equivalent)
  3. Any brain lesion thought to require immediate local therapy. Patients who undergo local treatment for such lesions identified by screening contrast brain MRI may still be eligible for the study based on criteria described under CNS inclusion criteria
  4. Known or suspected leptomeningeal disease (LMD)
  5. Poorly controlled seizures Unblinded Phase Crossover Inclusion Criteria - Participants who were randomized to the control arm (placebo + trastuzumab + capecitabine) must meet the following criteria to be eligible to crossover to the experimental arm.
  • 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.
  • Have an ECOG Performance Status of 0 or 1
  • Have a life expectancy of at least 6 months
  • Have adequate hepatic and renal function and hematologic parameters
  • Left ventricular ejection fraction (LVEF) ≥ 50%
  • CNS Inclusion - Based on screening brain magnetic resonance imaging (MRI), patients must have one of the following:
  1. No evidence of brain metastases ii. Untreated brain metastases not needing immediate local therapy iii. 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:
  1. 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.
  2. Other sites of disease assessable by RECIST 1.1 are present Unblinded Phase Crossover Exclusion Criteria - Participants who were randomized to the control arm (placebo + trastuzumab + capecitabine) will be excluded from the crossover to the experimental arm for any of the following reasons.
  • Discontinuation of study treatment due to an adverse event while on the double-blind phase of the study. If the adverse event leading to discontinuation of study treatment has resolved, the patient may be allowed to crossover with approval from the medical monitor.
  • History of exposure to the following cumulative doses of anthracyclines:
  • Doxorubicin > 360 mg/m^2
  • Epirubicin > 720 mg/m^2
  • Mitoxantrone > 120 mg/m^2
  • Idarubicin > 90 mg/m^2
  • Liposomal doxorubicin > 550 mg/m^2
  • History of allergic reactions to trastuzumab, capecitabine, or compounds chemically or biologically similar to tucatinib
  • Exceptions for Grade 1 or 2 infusion related reactions to trastuzumab that were successfully managed, or known allergy to one of the excipients in the study drugs
  • Have received treatment with any systemic anti-cancer therapy, non-CNS radiation, or experimental agent within 3 weeks prior to start of crossover therapy
  • Any toxicity related to prior cancer therapies that has not resolved to ≤ Grade 1, with the following exceptions:
  • Alopecia and neuropathy (must have resolved to ≤ Grade 2)
  • CHF (must have been ≤ Grade 1 in severity at the time of occurrence and must have resolved completely)
  • Anemia (must have resolved to ≤ Grade 2)
  • Have clinically significant cardiopulmonary disease
  • Have known myocardial infarction or unstable angina within 6 months prior to start of crossover therapy
  • Require therapy with warfarin or other coumarin derivatives
  • Inability to swallow pills or significant gastrointestinal disease which would preclude the adequate oral absorption of medications
  • Have used a strong CYP2C8 inhibitor within 5 half-lives of the inhibitor or have used a strong CYP2C8 or CYP34A inducer within 5 days prior to start of the crossover (tucatinib) treatment.
  • Known dihydropyrimidine dehydrogenase deficiency
  • Unable to undergo contract MRI of the brain
  • Have evidence within 2 years prior to start of crossover therapy of another malignancy that required systemic treatment
  • CNS Exclusion:
  • CNS Exclusion - Based on screening brain MRI, patients must not have any of the following:
  • 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)
  • Any brain lesion thought to require immediate local therapy. Patients who undergo local treatment for such lesions identified by screening contrast brain MRI may still be eligible for the study based on criteria described under CNS inclusion criteria
  • Known or suspected leptomeningeal disease (LMD)
  • Poorly controlled seizures

Trial locations and contacts

176 sites in 15 countries.

176 sites in 15 countries

United States81 sites

  • Winship Cancer Institute / Emory University School of Medicine

    Atlanta, Georgia, 30322

  • Northside Hospital

    Atlanta, Georgia, 30342

  • Augusta University

    Augusta, Georgia, 30912

  • University of Colorado Hospital / University of Colorado

    Aurora, Colorado, 80045-0510

  • Texas Oncology - Austin Midtown

    Austin, Texas, 78705

  • University of Maryland

    Baltimore, Maryland, 21201

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35249

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • UNC Lineberger Comprehensive Cancer Center / University of North Carolina

    Chapel Hill, North Carolina, 27599

  • Roper St. Francis Healthcare

    Charleston, South Carolina, 29414

  • Medical University of South Carolina/Hollings Cancer Center

    Charleston, South Carolina, 29425

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • University of Chicago

    Chicago, Illinois, 60637-1470

  • James Cancer Hospital / Ohio State University

    Columbus, Ohio, 43210

  • Texas Oncology Methodist

    Dallas, Texas, 75203

  • Texas Oncology - Denton South

    Denton, Texas, 76210

  • Henry Ford Health System

    Detroit, Michigan, 48202

  • City of Hope National Medical Center

    Duarte, California, 91010-3000

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Virginia Cancer Specialists, PC

    Fairfax, Virginia, 22031

  • Florida Cancer Specialists - South Region

    Fort Myers, Florida, 33901

  • The Center for Cancer and Blood Disorders: Fortworth

    Fort Worth, Texas, 76104

  • Cancer Treatment Centers of America - Phoenix

    Goodyear, Arizona, 85338

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

    Greenville, North Carolina, 27834

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Memorial Regional Hospital TRIO

    Hollywood, Florida, 33021

  • Texas Oncology - Houston Memorial City

    Houston, Texas, 77024

  • MD Anderson Cancer Center / University of Texas

    Houston, Texas, 77030-4095

  • Baylor Clinic

    Houston, Texas, 77030

  • Baptist MD Anderson Cancer Center

    Jacksonville, Florida, 32207

  • Saint Luke's Cancer Institute LLC

    Kansas City, Missouri, 64113

  • Wellmont Cancer Institute

    Kingsport, Tennessee, 37660

  • Dartmouth-Hitchcock Medical Center/ Norris Cotton Cancer Center

    Lebanon, New Hampshire, 03756

  • TRIO - Central Regulatory Office

    Los Angeles, California, 90095

  • UCLA Medical Center / David Geffen School of Medicine

    Los Angeles, California, 90095

  • Joe Arrington Cancer Research and Treatment Center

    Lubbock, Texas, 79410

  • Carbone Cancer Center / University of Wisconsin

    Madison, Wisconsin, 53792

  • University of Miami

    Miami, Florida, 33136

  • Mount Sinai Medical Center / Florida

    Miami Beach, Florida, 33140

  • Virginia Piper Cancer Institute

    Minneapolis, Minnesota, 55407

  • University of South Alabama - Mitchell Cancer Institute

    Mobile, Alabama, 36604

  • Tennessee Oncology - Nashville

    Nashville, Tennessee, 37203

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37204

  • Yale Cancer Center

    New Haven, Connecticut, 06520

  • Mount Sinai Beth Israel

    New York, New York, 10003

  • New York University (NYU) Cancer Institute

    New York, New York, 10016

  • Cancer Treatment Centers of America

    Newnan, Georgia, 30265

  • Illinois Cancer Specialists / Advocate Lutheran General Hospital

    Niles, Illinois, 60714

  • Nebraska Cancer Specialists

    Omaha, Nebraska, 68130

  • Orlando Health, Inc. TRIO

    Orlando, Florida, 32806

  • Paris Regional Medical Center / US Oncology

    Paris, Texas, 75460

  • University of Pennsylvania / Perelman Center for Advanced Medicine

    Philadelphia, Pennsylvania, 19104

  • Cancer Treatment Centers of America / Eastern Regional Medical Center

    Philadelphia, Pennsylvania, 19124

  • Arizona Oncology Associates, PC - HAL

    Phoenix, Arizona, 85016

  • Texas Oncology - Plano East

    Plano, Texas, 75075

  • Providence Portland Medical Center

    Portland, Oregon, 97213

  • Oregon Health and Science University

    Portland, Oregon, 97239-3098

  • Torrance Memorial Physician Network - TRIO

    Redondo Beach, California, 90277

  • Maryland Oncology Hematology, P.A.

    Rockville, Maryland, 20850

  • William Beaumont Hospital

    Royal Oak, Michigan, 48073

  • University of Utah

    Salt Lake City, Utah, 84112

  • Texas Oncology - San Antonio Medical Center Northeast

    San Antonio, Texas, 78212

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

  • University of California at San Francisco

    San Francisco, California, 94134

  • Kaiser Permanente San Marcos Medical Offices

    San Marcos, California, 92078

  • Central Coast Medical Oncology Corporation TRIO

    Santa Maria, California, 93454

  • Swedish Cancer Institute

    Seattle, Washington, 98104

  • Seattle Cancer Care Alliance / University of Washington

    Seattle, Washington, 98109-1023

  • Florida Cancer Specialists - North Region

    St. Petersburg, Florida, 33705

  • Stony Brook University Cancer Center

    Stony Brook, New York, 11794

  • H. Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

  • Montefiore Medical Center

    The Bronx, New York, 10467

  • US Oncology Central Regulatory

    The Woodlands, Texas, 77380

  • Northwest Cancer Specialists, P.C.

    Tualatin, Oregon, 97062

  • Carle Cancer Center

    Urbana, Illinois, 61801

  • Kaiser Permanente Medical Center Northern California

    Vallejo, California, 94589

  • Lombardi Cancer Center / Georgetown University Medical Center

    Washington D.C., District of Columbia, 20007

  • Texas Oncology - Deke Slayton Cancer Center

    Webster, Texas, 77598

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

    West Palm Beach, Florida, 33401

  • University of Kansas Cancer Center

    Westwood, Kansas, 66205

  • Shenandoah Oncology P.C.

    Winchester, Virginia, 22601

Other trials in United States

Canada11 sites

  • Tom Baker Cancer Centre

    Calgary, T2N 4N2

  • University of Alberta / Cross Cancer Institute

    Edmonton, T6G 1Z2

  • Queen Elizabeth II Health Sciences Centre

    Halifax, B3H 2Y9

  • Jewish General Hospital

    Montreal, H3T 1E2

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

    Québec, G1S 4L8

  • Allan Blair Cancer Centre

    Regina, S4T7T1

  • Saskatoon Cancer Centre

    Saskatoon, S7N 4H4

  • H. Bliss Murphy Cancer Centre

    St. John's, A1B 3V6

  • Sunnybrook Health Sciences Centre

    Toronto, M4N 3M5

  • University Health Network, Princess Margaret Hospital

    Toronto, M5G 2M9

  • British Columbia Cancer Agency - Vancouver Centre

    Vancouver, V5Z 4E6

Other trials in Canada

France11 sites

  • University Hospital of Besancon

    Besançon, 25030

  • Clinique Victor Hugo

    Le Mans, 72000

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

    Lyon, 69373

  • Institut Paoli Calmettes

    Marseille, 13273

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

    Paris, 75005

  • Centre Hospitalier Lyon Sud

    Pierre-Bénite, 69495

  • Institut Jean Godinot

    Reims, 51056

  • Centre Eugene Marquis

    Rennes, 35042

  • Hopitaux Universitaires de Strasbourg

    Strasbourg, 67200

  • Institut Claudius Regaud

    Toulouse, 31059

  • CHU Tours - Hopital Bretonneau

    Tours, 37044

Other trials in France

Spain10 sites

  • Hospital Universitario Vall d'Hebron

    Barcelona, 08035

  • Hospital Clinic i Provincial de Barcelona

    Barcelona, 08036

  • Hospital San Pedro de Alcantara

    Cáceres, 10002

  • Complejo Asistencial Universitario de Leon

    León, 24008

  • Hospital General Universitario Gregorio Marañon

    Madrid, 28007

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Hospital Son Espases

    Palma de Mallorca, 07010

  • Hospital Clinico Univ De Santiago De Compostela

    Santiago de Compostela, 15706

  • Hospital Arnau De Vilanova

    Valencia, 46015

  • Hospital Clinico Universitario Lozano Blesa de Zaragoza

    Zaragoza, 50009

Other trials in Spain

United Kingdom10 sites

  • Colchester Hospital University NHS Foundation Trust

    Colchester, C04 5JL

  • The Royal Marsden Hospital

    London, SW3 6JJ

  • Sarah Cannon Research Institute UK

    London, W1G 6AD

  • The Christie NHS Foundation Trust

    Manchester, M20 4BX

  • Mount Vernon Hospital, UK

    Northwood, HA6 2RN

  • Nottingham University Hospitals NHS Trust

    Nottingham, NG5 1PD

  • Peterborough City Hospital

    Peterborough, PE3 9GZ

  • Weston Park Hospital- UK

    Sheffield, S10 2SJ

  • The Royal Marsden Hospital (Surrey)

    Sutton, SM2 5PT

  • Royal Cornwall Hospitals NHS Trust

    Truro, TR1 3LQ

Other trials in United Kingdom

Australia9 sites

  • Austin Hospital

    Heidelberg, 3084

  • Cabrini Education and Research Precinct

    Malvern, 3144

  • Peter MacCallum Cancer Centre

    Melbourne, 3000

  • Breast Cancer Research Centre

    Nedlands, 6009

  • Mater Hospital

    North Sydney, 2060

  • Icon Cancer Care South Brisbane

    South Brisbane, 4101

  • Mater Health Services

    South Brisbane, 4101

  • Sunshine Hospital

    St Albans, 3021

  • Westmead Hospital

    Westmead, 2145

Other trials in Australia

Germany9 sites

  • Charite Universitatsmedizin Berlin

    Berlin, 10117

  • Universitatsklinikum Koln

    Cologne, 50937

  • Kliniken Essen-Mitte - Evang. Huyssens-Stiftung

    Essen, 45136

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

    Hamburg, 20246

  • Medizinische Hochschule Hannover

    Hanover, 30625

  • Universitatsklinikum Schleswig-Holstein

    Kiel, 24105

  • InVO- Institut fUr Versorgungsforschung in der onkologie GbR

    Koblenz, 56068

  • HOPE- Onkologisches Zentrum Rotkreuzklinikum

    München, 80639

  • Sana Klinikum Offenbach GmbH

    Offenbach, 63069

Other trials in Germany

Italy9 sites

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

    Bologna, 40138

  • Ospedale di Bolzano

    Bolzano, 39100

  • Presido Ospedaliero- Senatore Antonio Perrino

    Brindisi, 72100

  • Ospedale Ramazzini di Carpi

    Carpi, 41012

  • Ospedale Policlinico San Martino

    Genova, 16132

  • Istituto Europeo di Oncologia

    Milan, 20141

  • IRCSS Policlinico San Matteo

    Pavia, 27100

  • Azienda Ospedaliera S. Maria di Terni

    Terni, 05100

  • A.O.U. - Ospedali Riuniti di Ancona

    Torrette, 60126

Other trials in Italy

Israel7 sites

  • Rambam Health Corp.

    Haifa, 31096

  • Hadassah Medical Center

    Jerusalem, 91120

  • Meir Medical Center

    Kfar Saba, 44281

  • Rabin Medical Center

    Petah Tikva, 49414

  • Kaplan Medical Center

    Rehovot, 76100

  • Tel Aviv Sourasky Medical Center

    Tel Aviv, 64239

  • Sheba Medical Center

    Tel HaShomer, 52621

Other trials in Israel

Belgium5 sites

  • AZ Klina

    Brasschaat, 2930

  • Cliniques Universitaires Saint Luc

    Brussels, 1200

  • Grand Hopital de Charleroi

    Charleroi, 6000

  • Centre Hospitalier de l'Ardenne

    Libramont, 6800

  • CHU UCL Namur-Site de Saint Elisabeth

    Namur, 5000

Other trials in Belgium

Denmark5 sites

  • Aalborg Universitetshospital

    Aalborg, 9100

  • Rigs Hospiltalet

    Copenhagen, DK 2100

  • Herlev Hospital

    Herlev, 2730

  • Odense University Hospital

    Odense C, 5000

  • Sygehus Lillebaelt - Vejle Sygehus

    Vejle, 7100

Other trials in Denmark

Austria4 sites

  • LKH- Universitat Klinikum Graz

    Graz, 8036

  • Medizinische Universitat Innsbruck

    Innsbruck, 6020

  • KH d. Barmherzigen Schwestern Linz

    Linz, 4010

  • LKH Salzburg, Universitatsklinikum der PMU

    Salzburg, 5020

Other trials in Austria

Czechia2 sites

  • Fakultni nemocnice Hradec Kralove-oddeleni klinicke hematologie

    Hradec Králové, 500 05

  • Fakultni Nemocnice Olomouc (Fnol) - Onkologicka Klinika

    Olomouc, 77520

Other trials in Czechia

Portugal2 sites

  • Hospital Cuf Descobertas R. Mario Botas Parque das Nacoes

    Lisbon, 1998-018

  • Centro Hospitalar do Porto - Hospital Santo Antonio

    Porto, 4099-001

Other trials in Portugal

Switzerland1 site

  • Institute of Oncology of Southern Switzerland

    Bellinzona, 6500

Other trials in Switzerland

About this study

Official title: Phase 2 Randomized, Double-Blinded, Controlled Study of Tucatinib vs Placebo in Combination With Capecitabine and Trastuzumab in Patients With Pretreated Unresectable Locally Advanced or Metastatic HER2+ Breast Carcinoma

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.

Read more

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.

Read the 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.

Being tested
tucatinib, capecitabine, trastuzumab, placebo
Keywords
Tucatinib, Capecitabine, Trastuzumab, Xeloda, Herceptin, Breast Cancer, ARRY-380, ONT-380, HER2 Positive Breast Carcinoma, HER2 Positive Locally Advanced Breast Cancer, HER-2 Positive Breast Cancer, HER-2 Positive Breast Carcinoma, HER-2 Positive Locally Advanced Breast Cancer, Recurrent Breast Carcinoma, Stage IV Breast Cancer, Metastatic Breast Cancer, Breast Carcinoma, Metastatic Malignant Neoplasm in the Brain, Brain Metastases in Breast Cancer, Asymptomatic Brain Metastases in Breast Cancer
Medical subject headings
Breast Neoplasms, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • tucatinibDrug

    Also called ONT-380, ARRY-380

    300 mg orally twice daily

  • capecitabineDrug

    Also called Xeloda

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

  • trastuzumabDrug

    Also called Herceptin, Herceptin Hycleta

    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.

  • placeboDrug

    Oral dose twice daily

Study groups in NCT02614794
Study groupRoleWhat they receive
Tucatinib in combination with capecitabine & trastuzumabExperimentalTucatinib + capecitabine + trastuzumab
Receives: Drug: tucatinib; Drug: capecitabine; Drug: trastuzumab
Placebo in combination with capecitabine & trastuzumabActive comparatorPlacebo + capecitabine + trastuzumab
Receives: Drug: capecitabine; Drug: trastuzumab; Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 34.6 months

Secondary outcomes (18)

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

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

    Measured: 34.6 months

  2. Overall Survival (OS) at Time of Primary Analysis

    Defined as time from randomization to death from any cause

    Measured: 35.9 months

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

    Defined as achieving a best overall response of confirmed complete response (CR) or confirmed partial response (PR).

    Measured: 34.6 months

  4. ORR Per RECIST 1.1 as Determined by Investigator Assessment

    Defined as achieving a best overall response of confirmed CR or confirmed PR.

    Measured: 34.6 months

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

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

    Measured: 34.6 months

  6. Duration of Response (DOR) Per RECIST 1.1 as Determined by BICR

    Defined as the time from the first objective response to documented disease progression or death from any cause, whichever occurred first.

    Measured: 24.6 months

  7. DOR Per RECIST 1.1 as Determined by Investigator Assessment

    Defined as the time from the first objective response to documented disease progression or death from any cause, whichever occurred first.

    Measured: 33.2 months

  8. Clinical Benefit Rate (CBR) as Determined by BICR Per RECIST 1.1

    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).

    Measured: 34.6 months

  9. CBR Per RECIST 1.1 as Determined by Investigator Assessment

    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.

    Measured: 34.6 months

  10. Incidence of Adverse Events (AEs) at Time of Primary Analysis

    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.

    Measured: 36.1 months

  11. Frequency of Dose Modifications

    Measured: 35.1 months

  12. Incidence of Health Resources Utilization

    Cumulative incidence of health resource utilization, including length of stay, hospitalizations, and ER visits using the EQ-5D-5L questionnaire.

    Measured: 36.1 months

  13. Pharmacokinetic Measure: Ctrough of Tucatinib

    Individual plasma tucatinib concentrations at each sampling time

    Measured: 3.5 months

  14. Pharmacokinetic Measure: ONT-993

    Individual plasma primary metabolite concentrations at each sampling time

    Measured: 3.5 months

  15. Overall Survival (OS) at Time of Final Analysis

    Defined as time from randomization to death from any cause

    Measured: Up to 60.1 months

  16. PFS Per RECIST 1.1 as Determined by Investigator Assessment at Time of Final Analysis

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

    Measured: Up to 58.0 months

  17. Incidence of Adverse Events (AEs) at Time of Final Analysis

    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.

    Measured: Up to 60.1 months

  18. Frequency of Dose Modifications at Time of Final Analysis

    Measured: Up to 60.1 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Nov 2015 (estimated)
  2. Study start28 Jan 2016
  3. Primary completion4 Sep 2019
  4. Study completion11 Aug 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
612 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02614794
Sponsor's protocol ID
ONT-380-206
Other IDs
2015-002801-12, 2015
Acronym
HER2CLIMB
Status last verified
Jul 2023
First submitted
20 Nov 2015
Last updated
14 Aug 2023
Data monitoring committee
Yes
Expanded access
Available

Publications

  • 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.

    PubMed 39024777

  • 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.

    PubMed 36454580

  • 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.

    PubMed 34214937

  • 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.

    PubMed 32468955

  • 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.

    PubMed 31825569

  • 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.

    PubMed 29804905

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing tucatinib, capecitabine and trastuzumab in people with HER2 Positive Breast Cancer, run by Seagen Inc. at 176 sites in 15 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 176 sites in United States, Canada, France, Spain, United Kingdom and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (PFS) Per RECIST 1.1 as Determined by Blinded Independent Central Review (BICR) (time frame: 34.6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02614794, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2023.

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