Clinical trial NCT02614794: A Study of Tucatinib vs. Placebo in Combination With Capecitabine & Trastuzumab in Patients With Advanced HER2+ Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HER2 Positive Breast Cancer
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
Low Symptomatic Brain Metastases in Breast Cancer
Seattle Genetics
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
First posted: 2015-11-25
Enrollment: 612
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is being done to see if tucatinib works better than placebo to help patients who have a specific type of breast cancer called HER2 positive breast carcinoma. The breast cancer in this study is either metastatic (spread into other parts of the body) or cannot be removed completely with surgery. All patients in the study will get capecitabine and trastuzumab, two drugs that are often used to treat this cancer.

There are two parts to this study. The first part of the study is already complete. Patients were randomly assigned to get either tucatinib or placebo (a pill with no medicine). Since this part was "blinded," neither patients nor their doctors knew whether a patient got tucatinib or placebo.

The second part of the study is called the Unblinded Phase. In this part of the study, participants and their doctors know which drugs are being given. Participants who used to get or are currently getting placebo may be able to start taking tucatinib instead.

Each treatment cycle lasts 21 days. Patients will swallow tucatinib pills two times every day. They will swallow capecitabine pills two times a day during the first two weeks of each cycle. Patients will get trastuzumab injections from the study site staff on the first day of every cycle.

Detailed description: This is a randomized, international, multi-center study in patients with progressive unresectable locally advanced or metastatic HER2+ breast cancer who have had prior treatment with trastuzumab, pertuzumab and T-DM1. There are two phases to this trial: the Double-blind Phase and the Unblinded Phase. In the Double-blind phase, participants were randomized in a 2:1 ratio to receive tucatinib or placebo in combination with capecitabine and trastuzumab. In the Unblinded Phase, patients on placebo may be offered tucatinib.

Stratification factors include presence or history of treated or untreated brain metastases or brain lesions of equivocal significance (yes/no), Eastern Cooperative Oncology Group (ECOG) Performance Status (0 vs. 1), and region of world (US vs. Canada vs. Rest of World).

Safety assessments will be performed at a minimum of once every three weeks throughout study treatment and 30 days after the last dose of study drugs. Laboratory assessments will be performed locally at sites. Left ventricular ejection fraction will be assessed by MUGA or ECHO at screening and once every 12 weeks thereafter.

For the blinded phase, contrast brain MRI was performed at baseline. Efficacy assessments (CT of chest, abdomen and pelvis at a minimum) utilized RECIST 1.1 and included patients with evaluable tumors defined as measurable target lesions and non-measurable non-target lesions. RECIST assessment was performed at baseline, every 6 weeks for the first 24 weeks, and then every 9 weeks thereafter. Repeat MRI of the brain was required on this same schedule only in those patients with brain metastases identified at baseline. All treatment decisions were made based upon investigator assessment. All patients underwent a repeat MRI of the brain within 30 days of the end of treatment unless previously performed at time of disease progression.

For the unblinded phase, RECIST assessments will be performed per standard clinical practice as determined by investigator with a maximum interval of 12 weeks.

Eligibility 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

Primary outcomes:
measure: Progression-free Survival (PFS) Per RECIST 1.1 as Determined by Blinded Independent Central Review (BICR)
timeFrame: 34.6 months
Secondary outcomes:
measure: PFS in Patients With Brain Metastases at Baseline Using RECIST 1.1 as Determined by BICR
timeFrame: 34.6 months
measure: Overall Survival (OS) at Time of Primary Analysis
timeFrame: 35.9 months
measure: Confirmed Objective Response Rate (ORR) Per RECIST 1.1 as Determined by BICR
timeFrame: 34.6 months
measure: ORR Per RECIST 1.1 as Determined by Investigator Assessment
timeFrame: 34.6 months
measure: PFS Per RECIST 1.1 as Determined by Investigator Assessment at Time of Primary Analysis
timeFrame: 34.6 months
measure: Duration of Response (DOR) Per RECIST 1.1 as Determined by BICR
timeFrame: 24.6 months
measure: DOR Per RECIST 1.1 as Determined by Investigator Assessment
timeFrame: 33.2 months
measure: Clinical Benefit Rate (CBR) as Determined by BICR Per RECIST 1.1
timeFrame: 34.6 months
measure: CBR Per RECIST 1.1 as Determined by Investigator Assessment
timeFrame: 34.6 months
measure: Incidence of Adverse Events (AEs) at Time of Primary Analysis
timeFrame: 36.1 months
measure: Frequency of Dose Modifications
timeFrame: 35.1 months
measure: Incidence of Health Resources Utilization
timeFrame: 36.1 months
measure: Pharmacokinetic Measure: Ctrough of Tucatinib
timeFrame: 3.5 months
measure: Pharmacokinetic Measure: ONT-993
timeFrame: 3.5 months
measure: Overall Survival (OS) at Time of Final Analysis
timeFrame: Up to 60.1 months
measure: PFS Per RECIST 1.1 as Determined by Investigator Assessment at Time of Final Analysis
timeFrame: Up to 58.0 months
measure: Incidence of Adverse Events (AEs) at Time of Final Analysis
timeFrame: Up to 60.1 months
measure: Frequency of Dose Modifications at Time of Final Analysis
timeFrame: Up to 60.1 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Mobile
country: United States
facility: University of South Alabama - Mitchell Cancer Institute
state: Alabama
city: Goodyear
country: United States
facility: Cancer Treatment Centers of America - Phoenix
state: Arizona
city: Phoenix
country: United States
facility: Arizona Oncology Associates, PC - HAL
state: Arizona
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Los Angeles
country: United States
facility: TRIO - Central Regulatory Office
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center / David Geffen School of Medicine
state: California
city: Redondo Beach
country: United States
facility: Torrance Memorial Physician Network - TRIO
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: San Marcos
country: United States
facility: Kaiser Permanente San Marcos Medical Offices
state: California
city: Santa Maria
country: United States
facility: Central Coast Medical Oncology Corporation TRIO
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente Medical Center Northern California
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital / University of Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Washington
country: United States
facility: Lombardi Cancer Center / Georgetown University Medical Center
state: District of Columbia
city: Fort Myers
country: United States
facility: Florida Cancer Specialists - South Region
state: Florida
city: Hollywood
country: United States
facility: Memorial Regional Hospital TRIO
state: Florida
city: Jacksonville
country: United States
facility: Baptist MD Anderson Cancer Center
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center / Florida
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Orlando
country: United States
facility: Orlando Health, Inc. TRIO
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists - North Region
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: West Palm Beach
country: United States
facility: Florida Cancer Specialists - East West Palm Beach, FL (SCRI)
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute / Emory University School of Medicine
state: Georgia
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Newnan
country: United States
facility: Cancer Treatment Centers of America
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Niles
country: United States
facility: Illinois Cancer Specialists / Advocate Lutheran General Hospital
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center
state: Illinois
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Rockville
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's Cancer Institute LLC
state: Missouri
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center/ Norris Cotton Cancer Center
state: New Hampshire
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Mount Sinai Beth Israel
state: New York
city: New York
country: United States
facility: New York University (NYU) Cancer Institute
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: UNC Lineberger Comprehensive Cancer Center / University of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Greenville
country: United States
facility: Leo W. Jenkins Cancer Services / Brody School of Medicine East Carolina University
state: North Carolina
city: Columbus
country: United States
facility: James Cancer Hospital / Ohio State University
state: Ohio
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Tualatin
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania / Perelman Center for Advanced Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: Cancer Treatment Centers of America / Eastern Regional Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Roper St. Francis Healthcare
state: South Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina/Hollings Cancer Center
state: South Carolina
city: Kingsport
country: United States
facility: Wellmont Cancer Institute
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology - Nashville
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology - Austin Midtown
state: Texas
city: Dallas
country: United States
facility: Texas Oncology Methodist
state: Texas
city: Denton
country: United States
facility: Texas Oncology - Denton South
state: Texas
city: Fort Worth
country: United States
facility: The Center for Cancer and Blood Disorders: Fortworth
state: Texas
city: Houston
country: United States
facility: Texas Oncology - Houston Memorial City
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center / University of Texas
state: Texas
city: Houston
country: United States
facility: Baylor Clinic
state: Texas
city: Lubbock
country: United States
facility: Joe Arrington Cancer Research and Treatment Center
state: Texas
city: Paris
country: United States
facility: Paris Regional Medical Center / US Oncology
state: Texas
city: Plano
country: United States
facility: Texas Oncology - Plano East
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology - San Antonio Medical Center Northeast
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: The Woodlands
country: United States
facility: US Oncology Central Regulatory
state: Texas
city: Webster
country: United States
facility: Texas Oncology - Deke Slayton Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Winchester
country: United States
facility: Shenandoah Oncology P.C.
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance / University of Washington
state: Washington
city: Madison
country: United States
facility: Carbone Cancer Center / University of Wisconsin
state: Wisconsin
city: Heidelberg
country: Australia
facility: Austin Hospital
city: Malvern
country: Australia
facility: Cabrini Education and Research Precinct
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
city: Nedlands
country: Australia
facility: Breast Cancer Research Centre
city: North Sydney
country: Australia
facility: Mater Hospital
city: South Brisbane
country: Australia
facility: Icon Cancer Care South Brisbane
city: South Brisbane
country: Australia
facility: Mater Health Services
city: St Albans
country: Australia
facility: Sunshine Hospital
city: Westmead
country: Australia
facility: Westmead Hospital
city: Graz
country: Austria
facility: LKH- Universitat Klinikum Graz
city: Innsbruck
country: Austria
facility: Medizinische Universitat Innsbruck
city: Linz
country: Austria
facility: KH d. Barmherzigen Schwestern Linz
city: Salzburg
country: Austria
facility: LKH Salzburg, Universitatsklinikum der PMU
city: Brasschaat
country: Belgium
facility: AZ Klina
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint Luc
city: Charleroi
country: Belgium
facility: Grand Hopital de Charleroi
city: Libramont
country: Belgium
facility: Centre Hospitalier de l'Ardenne
city: Namur
country: Belgium
facility: CHU UCL Namur-Site de Saint Elisabeth
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
city: Edmonton
country: Canada
facility: University of Alberta / Cross Cancer Institute
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre
city: Montreal
country: Canada
facility: Jewish General Hospital
city: Quebec
country: Canada
facility: Hopital du Saint-Sacrement, CHU de Quebec-Universite Laval
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
city: St John's
country: Canada
facility: H. Bliss Murphy Cancer Centre
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
city: Toronto
country: Canada
facility: University Health Network, Princess Margaret Hospital
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency - Vancouver Centre
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove-oddeleni klinicke hematologie
city: Olomouc
country: Czechia
facility: Fakultni Nemocnice Olomouc (Fnol) - Onkologicka Klinika
city: Aalborg
country: Denmark
facility: Aalborg Universitetshospital
city: Copenhagen
country: Denmark
facility: Rigs Hospiltalet
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Odense C
country: Denmark
facility: Odense University Hospital
city: Vejle
country: Denmark
facility: Sygehus Lillebaelt - Vejle Sygehus
city: Besancon cedex
country: France
facility: University Hospital of Besancon
city: Le Mans
country: France
facility: Clinique Victor Hugo
city: Lyon
country: France
facility: Centre Leon Berard - Centre regional de lutte contre le cancer Rhone-Alpes
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Paris
country: France
facility: Institute Curie - Centre de Lutte Contre Le Cancer CLCC de Paris
city: Pierre Bénite Cedex
country: France
facility: Centre Hospitalier Lyon Sud
city: REIMS Cedex
country: France
facility: Institut Jean Godinot
city: Rennes Cedex
country: France
facility: Centre Eugene Marquis
city: Strasbourg
country: France
facility: Hopitaux Universitaires de Strasbourg
city: Toulouse Cedex 9
country: France
facility: Institut Claudius Regaud
city: TOURS Cedex 09
country: France
facility: CHU Tours - Hopital Bretonneau
city: Berlin
country: Germany
facility: Charite Universitatsmedizin Berlin
city: Essen
country: Germany
facility: Kliniken Essen-Mitte - Evang. Huyssens-Stiftung
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf (UKE) - Onkologisches Zentrum - Interdisziplinaere Klinik und Poliklinik fuer Stammzelltransplantation
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Kiel
country: Germany
facility: Universitatsklinikum Schleswig-Holstein
city: Koblenz
country: Germany
facility: InVO- Institut fUr Versorgungsforschung in der onkologie GbR
city: Köln
country: Germany
facility: Universitatsklinikum Koln
city: Munchen
country: Germany
facility: HOPE- Onkologisches Zentrum Rotkreuzklinikum
city: Offenbach am Main
country: Germany
facility: Sana Klinikum Offenbach GmbH
city: Haifa
country: Israel
facility: Rambam Health Corp.
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Tel Hashomer
country: Israel
facility: Sheba Medical Center
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi
city: Bolzano
country: Italy
facility: Ospedale di Bolzano
city: Brindisi
country: Italy
facility: Presido Ospedaliero- Senatore Antonio Perrino
city: Carpi
country: Italy
facility: Ospedale Ramazzini di Carpi
city: Genova
country: Italy
facility: Ospedale Policlinico San Martino
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Pavia
country: Italy
facility: IRCSS Policlinico San Matteo
city: Terni
country: Italy
facility: Azienda Ospedaliera S. Maria di Terni
city: Torrette
country: Italy
facility: A.O.U. - Ospedali Riuniti di Ancona
city: Lisboa
country: Portugal
facility: Hospital Cuf Descobertas R. Mario Botas Parque das Nacoes
city: Porto
country: Portugal
facility: Centro Hospitalar do Porto - Hospital Santo Antonio
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
city: Caceres
country: Spain
facility: Hospital San Pedro de Alcantara
city: Leon
country: Spain
facility: Complejo Asistencial Universitario de Leon
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Palma de Mallorca
country: Spain
facility: Hospital Son Espases
city: Santiago de Compostela
country: Spain
facility: Hospital Clinico Univ De Santiago De Compostela
city: Valencia
country: Spain
facility: Hospital Arnau De Vilanova
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario Lozano Blesa de Zaragoza
city: Bellinzona
country: Switzerland
facility: Institute of Oncology of Southern Switzerland
city: Colchester
country: United Kingdom
facility: Colchester Hospital University NHS Foundation Trust
city: London
country: United Kingdom
facility: The Royal Marsden Hospital
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute UK
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Northwood
country: United Kingdom
facility: Mount Vernon Hospital, UK
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Peterborough
country: United Kingdom
facility: Peterborough City Hospital
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital- UK
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital (Surrey)
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospitals NHS Trust
Study officials:
affiliation: Seagen Inc.
name: Jorge Ramos, DO
role: STUDY_DIRECTOR
affiliation: Seagen Inc.
name: Corinna Palanca-Wessels, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.