A Study of Tucatinib vs. Placebo in Combination With Capecitabine & Trastuzumab in Patients With Advanced HER2+ Breast Cancer (HER2CLIMB)

• ClinicalTrials.gov Identifier: NCT02614794
• Recruitment Status: Completed
• First Posted: November 25, 2015
• Results First Posted: September 28, 2020
• Last Update Posted: August 14, 2023
• Sponsor: Seagen Inc.
• Information provided by (Responsible Party): Seagen Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
HER2 Positive Breast Cancer	Drug: tucatinib; Drug: capecitabine; Drug: trastuzumab; Drug: placebo	Phase 2

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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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 612 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Masking applied only during the Double-blind phase of the trial. The Unblinded Phase is open-label.
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: January 28, 2016
• Actual Primary Completion Date: September 4, 2019
• Actual Study Completion Date: August 11, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Tucatinib in combination with capecitabine & trastuzumab; Tucatinib + capecitabine + trastuzumab	Drug: tucatinib; 300 mg orally twice daily; Other Name: ONT-380, ARRY-380; Drug: capecitabine; 1000 mg/m2 orally twice daily on Days 1-14 of each 21-day cycle; Other Name: Xeloda; Drug: 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.; Other Name: Herceptin, Herceptin Hycleta
Active Comparator: Placebo in combination with capecitabine & trastuzumab; Placebo + capecitabine + trastuzumab	Drug: capecitabine; 1000 mg/m2 orally twice daily on Days 1-14 of each 21-day cycle; Other Name: Xeloda; Drug: 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.; Other Name: Herceptin, Herceptin Hycleta; Drug: placebo; Oral dose twice daily

Outcome Measures

Primary Outcome Measures :

1. Progression-free Survival (PFS) Per RECIST 1.1 as Determined by Blinded Independent Central Review (BICR) [ Time Frame: 34.6 months ]
   Defined as the time from the date of randomization to the date of documented disease progression.

Secondary Outcome Measures :

1. PFS in Patients With Brain Metastases at Baseline Using RECIST 1.1 as Determined by BICR [ Time Frame: 34.6 months ]
   Defined as the time from the date of randomization to the date of documented disease progression.
2. Overall Survival (OS) at Time of Primary Analysis [ Time Frame: 35.9 months ]
   Defined as time from randomization to death from any cause
3. Confirmed Objective Response Rate (ORR) Per RECIST 1.1 as Determined by BICR [ Time Frame: 34.6 months ]
   Defined as achieving a best overall response of confirmed complete response (CR) or confirmed partial response (PR).
4. ORR Per RECIST 1.1 as Determined by Investigator Assessment [ Time Frame: 34.6 months ]
   Defined as achieving a best overall response of confirmed CR or confirmed PR.
5. PFS Per RECIST 1.1 as Determined by Investigator Assessment at Time of Primary Analysis [ Time Frame: 34.6 months ]
   Defined as the time from the date of randomization to the date of documented disease progression
6. Duration of Response (DOR) Per RECIST 1.1 as Determined by BICR [ Time Frame: 24.6 months ]
   Defined as the time from the first objective response to documented disease progression or death from any cause, whichever occurred first.
7. DOR Per RECIST 1.1 as Determined by Investigator Assessment [ Time Frame: 33.2 months ]
   Defined as the time from the first objective response to documented disease progression or death from any cause, whichever occurred first.
8. Clinical Benefit Rate (CBR) as Determined by BICR Per RECIST 1.1 [ Time Frame: 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).
9. CBR Per RECIST 1.1 as Determined by Investigator Assessment [ Time Frame: 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.
10. Incidence of Adverse Events (AEs) at Time of Primary Analysis [ Time Frame: 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.
11. Frequency of Dose Modifications [ Time Frame: 35.1 months ]
12. Incidence of Health Resources Utilization [ Time Frame: 36.1 months ]
    Cumulative incidence of health resource utilization, including length of stay, hospitalizations, and ER visits using the EQ-5D-5L questionnaire.
13. Pharmacokinetic Measure: Ctrough of Tucatinib [ Time Frame: 3.5 months ]
    Individual plasma tucatinib concentrations at each sampling time
14. Pharmacokinetic Measure: ONT-993 [ Time Frame: 3.5 months ]
    Individual plasma primary metabolite concentrations at each sampling time
15. Overall Survival (OS) at Time of Final Analysis [ Time Frame: Up to 60.1 months ]
    Defined as time from randomization to death from any cause
16. PFS Per RECIST 1.1 as Determined by Investigator Assessment at Time of Final Analysis [ Time Frame: Up to 58.0 months ]
    Defined as the time from the date of randomization to the date of documented disease progression
17. Incidence of Adverse Events (AEs) at Time of Final Analysis [ Time Frame: 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.
18. Frequency of Dose Modifications at Time of Final Analysis [ Time Frame: Up to 60.1 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

     1. Brain metastases previously treated with local therapy may either be stable since treatment or may have progressed since prior local CNS therapy
     2. 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

  4. 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:

  i. 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

  o 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

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35249

University of South Alabama - Mitchell Cancer Institute

Mobile, Alabama, United States, 36604

United States, Arizona

Cancer Treatment Centers of America - Phoenix

Goodyear, Arizona, United States, 85338

Arizona Oncology Associates, PC - HAL

Phoenix, Arizona, United States, 85016

United States, California

City of Hope National Medical Center

Duarte, California, United States, 91010-3000

TRIO - Central Regulatory Office

Los Angeles, California, United States, 90095

UCLA Medical Center / David Geffen School of Medicine

Los Angeles, California, United States, 90095

Torrance Memorial Physician Network - TRIO

Redondo Beach, California, United States, 90277

University of California at San Francisco

San Francisco, California, United States, 94134

Kaiser Permanente San Marcos Medical Offices

San Marcos, California, United States, 92078

Central Coast Medical Oncology Corporation TRIO

Santa Maria, California, United States, 93454

Kaiser Permanente Medical Center Northern California

Vallejo, California, United States, 94589

United States, Colorado

University of Colorado Hospital / University of Colorado

Aurora, Colorado, United States, 80045-0510

United States, Connecticut

Yale Cancer Center

New Haven, Connecticut, United States, 06520

United States, District of Columbia

Lombardi Cancer Center / Georgetown University Medical Center

Washington, District of Columbia, United States, 20007

United States, Florida

Florida Cancer Specialists - South Region

Fort Myers, Florida, United States, 33901

Memorial Regional Hospital TRIO

Hollywood, Florida, United States, 33021

Baptist MD Anderson Cancer Center

Jacksonville, Florida, United States, 32207

Mount Sinai Medical Center / Florida

Miami Beach, Florida, United States, 33140

University of Miami

Miami, Florida, United States, 33136

Orlando Health, Inc. TRIO

Orlando, Florida, United States, 32806

Florida Cancer Specialists - North Region

Saint Petersburg, Florida, United States, 33705

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States, 33612

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

West Palm Beach, Florida, United States, 33401

United States, Georgia

Winship Cancer Institute / Emory University School of Medicine

Atlanta, Georgia, United States, 30322

Northside Hospital

Atlanta, Georgia, United States, 30342

Augusta University

Augusta, Georgia, United States, 30912

Cancer Treatment Centers of America

Newnan, Georgia, United States, 30265

United States, Illinois

Rush University Medical Center

Chicago, Illinois, United States, 60612

University of Chicago

Chicago, Illinois, United States, 60637-1470

Illinois Cancer Specialists / Advocate Lutheran General Hospital

Niles, Illinois, United States, 60714

Carle Cancer Center

Urbana, Illinois, United States, 61801

United States, Kansas

University of Kansas Cancer Center

Westwood, Kansas, United States, 66205

United States, Maryland

University of Maryland

Baltimore, Maryland, United States, 21201

Maryland Oncology Hematology, P.A.

Rockville, Maryland, United States, 20850

United States, Massachusetts

Dana Farber Cancer Institute

Boston, Massachusetts, United States, 02215

United States, Michigan

Henry Ford Health System

Detroit, Michigan, United States, 48202

William Beaumont Hospital

Royal Oak, Michigan, United States, 48073

United States, Minnesota

Virginia Piper Cancer Institute

Minneapolis, Minnesota, United States, 55407

United States, Missouri

Saint Luke's Cancer Institute LLC

Kansas City, Missouri, United States, 64113

United States, Nebraska

Nebraska Cancer Specialists

Omaha, Nebraska, United States, 68130

United States, New Hampshire

Dartmouth-Hitchcock Medical Center/ Norris Cotton Cancer Center

Lebanon, New Hampshire, United States, 03756

United States, New Jersey

Hackensack University Medical Center

Hackensack, New Jersey, United States, 07601

United States, New York

Montefiore Medical Center

Bronx, New York, United States, 10467

Mount Sinai Beth Israel

New York, New York, United States, 10003

New York University (NYU) Cancer Institute

New York, New York, United States, 10016

Stony Brook University Cancer Center

Stony Brook, New York, United States, 11794

United States, North Carolina

UNC Lineberger Comprehensive Cancer Center / University of North Carolina

Chapel Hill, North Carolina, United States, 27599

Duke University Medical Center

Durham, North Carolina, United States, 27710

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

Greenville, North Carolina, United States, 27834

United States, Ohio

James Cancer Hospital / Ohio State University

Columbus, Ohio, United States, 43210

United States, Oregon

Providence Portland Medical Center

Portland, Oregon, United States, 97213

Oregon Health and Science University

Portland, Oregon, United States, 97239-3098

Northwest Cancer Specialists, P.C.

Tualatin, Oregon, United States, 97062

United States, Pennsylvania

University of Pennsylvania / Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, United States, 19104

Cancer Treatment Centers of America / Eastern Regional Medical Center

Philadelphia, Pennsylvania, United States, 19124

United States, South Carolina

Roper St. Francis Healthcare

Charleston, South Carolina, United States, 29414

Medical University of South Carolina/Hollings Cancer Center

Charleston, South Carolina, United States, 29425

United States, Tennessee

Wellmont Cancer Institute

Kingsport, Tennessee, United States, 37660

Tennessee Oncology - Nashville

Nashville, Tennessee, United States, 37203

Vanderbilt University Medical Center

Nashville, Tennessee, United States, 37204

United States, Texas

Texas Oncology - Austin Midtown

Austin, Texas, United States, 78705

Texas Oncology Methodist

Dallas, Texas, United States, 75203

Texas Oncology - Denton South

Denton, Texas, United States, 76210

The Center for Cancer and Blood Disorders: Fortworth

Fort Worth, Texas, United States, 76104

Texas Oncology - Houston Memorial City

Houston, Texas, United States, 77024

MD Anderson Cancer Center / University of Texas

Houston, Texas, United States, 77030-4095

Baylor Clinic

Houston, Texas, United States, 77030

Joe Arrington Cancer Research and Treatment Center

Lubbock, Texas, United States, 79410

Paris Regional Medical Center / US Oncology

Paris, Texas, United States, 75460

Texas Oncology - Plano East

Plano, Texas, United States, 75075

Texas Oncology - San Antonio Medical Center Northeast

San Antonio, Texas, United States, 78212

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States, 78229

US Oncology Central Regulatory

The Woodlands, Texas, United States, 77380

Texas Oncology - Deke Slayton Cancer Center

Webster, Texas, United States, 77598

United States, Utah

University of Utah

Salt Lake City, Utah, United States, 84112

United States, Virginia

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States, 22031

Shenandoah Oncology P.C.

Winchester, Virginia, United States, 22601

United States, Washington

Swedish Cancer Institute

Seattle, Washington, United States, 98104

Seattle Cancer Care Alliance / University of Washington

Seattle, Washington, United States, 98109-1023

United States, Wisconsin

Carbone Cancer Center / University of Wisconsin

Madison, Wisconsin, United States, 53792

Australia

Austin Hospital

Heidelberg, Australia, 3084

Cabrini Education and Research Precinct

Malvern, Australia, 3144

Peter MacCallum Cancer Centre

Melbourne, Australia, 3000

Breast Cancer Research Centre

Nedlands, Australia, 6009

Mater Hospital

North Sydney, Australia, 2060

Icon Cancer Care South Brisbane

South Brisbane, Australia, 4101

Mater Health Services

South Brisbane, Australia, 4101

Sunshine Hospital

St Albans, Australia, 3021

Westmead Hospital

Westmead, Australia, 2145

Austria

LKH- Universitat Klinikum Graz

Graz, Austria, 8036

Medizinische Universitat Innsbruck

Innsbruck, Austria, 6020

KH d. Barmherzigen Schwestern Linz

Linz, Austria, 4010

LKH Salzburg, Universitatsklinikum der PMU

Salzburg, Austria, 5020

Belgium

AZ Klina

Brasschaat, Belgium, 2930

Cliniques Universitaires Saint Luc

Brussels, Belgium, 1200

Grand Hopital de Charleroi

Charleroi, Belgium, 6000

Centre Hospitalier de l'Ardenne

Libramont, Belgium, 6800

CHU UCL Namur-Site de Saint Elisabeth

Namur, Belgium, 5000

Canada

Tom Baker Cancer Centre

Calgary, Canada, T2N 4N2

University of Alberta / Cross Cancer Institute

Edmonton, Canada, T6G 1Z2

Queen Elizabeth II Health Sciences Centre

Halifax, Canada, B3H 2Y9

Jewish General Hospital

Montreal, Canada, H3T 1E2

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

Quebec, Canada, G1S 4L8

Allan Blair Cancer Centre

Regina, Canada, S4T7T1

Saskatoon Cancer Centre

Saskatoon, Canada, S7N 4H4

H. Bliss Murphy Cancer Centre

St John's, Canada, A1B 3V6

Sunnybrook Health Sciences Centre

Toronto, Canada, M4N 3M5

University Health Network, Princess Margaret Hospital

Toronto, Canada, M5G 2M9

British Columbia Cancer Agency - Vancouver Centre

Vancouver, Canada, V5Z 4E6

Czechia

Fakultni nemocnice Hradec Kralove-oddeleni klinicke hematologie

Hradec Kralove, Czechia, 500 05

Fakultni Nemocnice Olomouc (Fnol) - Onkologicka Klinika

Olomouc, Czechia, 77520

Denmark

Aalborg Universitetshospital

Aalborg, Denmark, 9100

Rigs Hospiltalet

Copenhagen, Denmark, DK 2100

Herlev Hospital

Herlev, Denmark, 2730

Odense University Hospital

Odense C, Denmark, 5000

Sygehus Lillebaelt - Vejle Sygehus

Vejle, Denmark, 7100

France

University Hospital of Besancon

Besancon cedex, France, 25030

Clinique Victor Hugo

Le Mans, France, 72000

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

Lyon, France, 69373

Institut Paoli Calmettes

Marseille, France, 13273

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

Paris, France, 75005

Centre Hospitalier Lyon Sud

Pierre Bénite Cedex, France, 69495

Institut Jean Godinot

REIMS Cedex, France, 51056

Centre Eugene Marquis

Rennes Cedex, France, 35042

Hopitaux Universitaires de Strasbourg

Strasbourg, France, 67200

Institut Claudius Regaud

Toulouse Cedex 9, France, 31059

CHU Tours - Hopital Bretonneau

TOURS Cedex 09, France, 37044

Germany

Charite Universitatsmedizin Berlin

Berlin, Germany, 10117

Kliniken Essen-Mitte - Evang. Huyssens-Stiftung

Essen, Germany, 45136

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

Hamburg, Germany, 20246

Medizinische Hochschule Hannover

Hannover, Germany, 30625

Universitatsklinikum Schleswig-Holstein

Kiel, Germany, 24105

InVO- Institut fUr Versorgungsforschung in der onkologie GbR

Koblenz, Germany, 56068

Universitatsklinikum Koln

Köln, Germany, 50937

HOPE- Onkologisches Zentrum Rotkreuzklinikum

Munchen, Germany, 80639

Sana Klinikum Offenbach GmbH

Offenbach am Main, Germany, 63069

Israel

Rambam Health Corp.

Haifa, Israel, 31096

Hadassah Medical Center

Jerusalem, Israel, 91120

Meir Medical Center

Kfar Saba, Israel, 44281

Rabin Medical Center

Petach Tikva, Israel, 49414

Kaplan Medical Center

Rehovot, Israel, 76100

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel, 64239

Sheba Medical Center

Tel Hashomer, Israel, 52621

Italy

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

Bologna, Italy, 40138

Ospedale di Bolzano

Bolzano, Italy, 39100

Presido Ospedaliero- Senatore Antonio Perrino

Brindisi, Italy, 72100

Ospedale Ramazzini di Carpi

Carpi, Italy, 41012

Ospedale Policlinico San Martino

Genova, Italy, 16132

Istituto Europeo di Oncologia

Milano, Italy, 20141

IRCSS Policlinico San Matteo

Pavia, Italy, 27100

Azienda Ospedaliera S. Maria di Terni

Terni, Italy, 05100

A.O.U. - Ospedali Riuniti di Ancona

Torrette, Italy, 60126

Portugal

Hospital Cuf Descobertas R. Mario Botas Parque das Nacoes

Lisboa, Portugal, 1998-018

Centro Hospitalar do Porto - Hospital Santo Antonio

Porto, Portugal, 4099-001

Spain

Hospital Universitario Vall d'Hebron

Barcelona, Spain, 08035

Hospital Clinic i Provincial de Barcelona

Barcelona, Spain, 08036

Hospital San Pedro de Alcantara

Caceres, Spain, 10002

Complejo Asistencial Universitario de Leon

Leon, Spain, 24008

Hospital General Universitario Gregorio Marañon

Madrid, Spain, 28007

Hospital Universitario 12 de Octubre

Madrid, Spain, 28041

Hospital Son Espases

Palma de Mallorca, Spain, 07010

Hospital Clinico Univ De Santiago De Compostela

Santiago de Compostela, Spain, 15706

Hospital Arnau De Vilanova

Valencia, Spain, 46015

Hospital Clinico Universitario Lozano Blesa de Zaragoza

Zaragoza, Spain, 50009

Switzerland

Institute of Oncology of Southern Switzerland

Bellinzona, Switzerland, 6500

United Kingdom

Colchester Hospital University NHS Foundation Trust

Colchester, United Kingdom, C04 5JL

The Royal Marsden Hospital

London, United Kingdom, SW3 6JJ

Sarah Cannon Research Institute UK

London, United Kingdom, W1G 6AD

The Christie NHS Foundation Trust

Manchester, United Kingdom, M20 4BX

Mount Vernon Hospital, UK

Northwood, United Kingdom, HA6 2RN

Nottingham University Hospitals NHS Trust

Nottingham, United Kingdom, NG5 1PD

Peterborough City Hospital

Peterborough, United Kingdom, PE3 9GZ

Weston Park Hospital- UK

Sheffield, United Kingdom, S10 2SJ

The Royal Marsden Hospital (Surrey)

Sutton, United Kingdom, SM2 5PT

Royal Cornwall Hospitals NHS Trust

Truro, United Kingdom, TR1 3LQ

Sponsors and Collaborators

Seagen Inc.

Investigators

• Study Director: Jorge Ramos, DO; Seagen Inc.
• Study Director: Corinna Palanca-Wessels, MD, PhD; Seagen Inc.

  Study Documents (Full-Text)

Documents provided by Seagen Inc.:

Study Protocol  [PDF] June 30, 2021

Statistical Analysis Plan  [PDF] August 7, 2019

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Erratum In: N Engl J Med. 2020 Feb 6;382(6):586.

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.

• Responsible Party: Seagen Inc.
• ClinicalTrials.gov Identifier: NCT02614794
• Other Study ID Numbers: ONT-380-206; 2015-002801-12 ( EudraCT Number )
• First Posted: November 25, 2015
• Results First Posted: September 28, 2020
• Last Update Posted: August 14, 2023
• Last Verified: July 2023

Keywords provided by Seagen Inc.:

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; Low Symptomatic Brain Metastases in Breast Cancer; Seattle Genetics

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Capecitabine; Trastuzumab; Tucatinib; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Enzyme Inhibitors