A Study of Trastuzumab Emtansine in Comparison With Treatment of Physician's Choice in Participants With HER2-positive Breast Cancer Who Have Received at Least Two Prior Regimens of HER2-directed Therapy

NCT ID: NCT01419197

Last Updated: 2016-10-12

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

602 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-09-30

Study Completion Date

2015-08-31

Brief Summary

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This randomized, multicenter, 2-arm, open-label study (TH3RESA) will evaluate the efficacy and safety of trastuzumab emtansine (T-DM1) in comparison with treatment of the physician's choice in participants with metastatic or unresectable locally advanced/recurrent human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Eligible participants will be randomized to receive either trastuzumab emtansine 3.6 mg/kg intravenously every 21 days or treatment of the physician's choice. Participants continue to receive study treatment until disease progression or unacceptable toxicity occurs. This study is also known under Roche study protocol number BO25734.

Detailed Description

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Conditions

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Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Trastuzumab emtansine

Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.

Group Type EXPERIMENTAL

Trastuzumab emtansine

Intervention Type DRUG

The dose was calculated based on the patient's Baseline weight on Day 1 of each 3-week treatment cycle. The same dose was administered in subsequent cycles if the patient's weight stayed within 10% of the Baseline weight. If there was a weight change \> 10%, the dose was adjusted accordingly and the recorded weight became the new Baseline weight. Trastuzumab emtansine was provided as a single-use lyophilized formulation.

Treatment of physician's choice

Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.

Group Type ACTIVE_COMPARATOR

Treatment of physician's choice

Intervention Type DRUG

The treatment of physician's choice (TPC) was a protocol-specified approved or standard of care therapy or combination of therapies, based on frequently used regimens for late-line HER2-positive metastatic breast cancer treatment after receipt of both trastuzumab- and lapatinib-containing regimens. The therapies included single-agent chemotherapy, single-agent (e.g., tamoxifen or aromatase inhibitor) or dual-agent (e.g., aromatase inhibitor with luteinizing hormone releasing hormone \[LHRH\] agonist) hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.

Participants who had documented progressive disease (PD) were eligible to switch treatment to receive trastuzumab emtansine 3.6 mg/kg. Participants who switched treatment remained on trastuzumab emtansine treatment until another PD event or unmanageable toxicity.

The formulation, storage, and preparation of all TPC were as per the appropriate package insert or national prescribing information.

Interventions

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Trastuzumab emtansine

The dose was calculated based on the patient's Baseline weight on Day 1 of each 3-week treatment cycle. The same dose was administered in subsequent cycles if the patient's weight stayed within 10% of the Baseline weight. If there was a weight change \> 10%, the dose was adjusted accordingly and the recorded weight became the new Baseline weight. Trastuzumab emtansine was provided as a single-use lyophilized formulation.

Intervention Type DRUG

Treatment of physician's choice

The treatment of physician's choice (TPC) was a protocol-specified approved or standard of care therapy or combination of therapies, based on frequently used regimens for late-line HER2-positive metastatic breast cancer treatment after receipt of both trastuzumab- and lapatinib-containing regimens. The therapies included single-agent chemotherapy, single-agent (e.g., tamoxifen or aromatase inhibitor) or dual-agent (e.g., aromatase inhibitor with luteinizing hormone releasing hormone \[LHRH\] agonist) hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.

Participants who had documented progressive disease (PD) were eligible to switch treatment to receive trastuzumab emtansine 3.6 mg/kg. Participants who switched treatment remained on trastuzumab emtansine treatment until another PD event or unmanageable toxicity.

The formulation, storage, and preparation of all TPC were as per the appropriate package insert or national prescribing information.

Intervention Type DRUG

Other Intervention Names

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Kadcyla T-DM1

Eligibility Criteria

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Inclusion Criteria

* Adult participants ≥ 18 years of age.
* Histologically or cytologically documented breast cancer.
* Metastatic or unresectable locally advanced/recurrent breast cancer.
* HER2-positive disease by prospective laboratory confirmation.
* Disease progression on the last regimen received as defined by the investigator.
* Prior treatment with an trastuzumab, a taxane, and lapatinib.
* Disease progression after at least two regimens of HER2-directed therapy in the metastatic or unresectable locally advanced/recurrent setting.
* Adequate organ function, as evidenced by laboratory results.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
* Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram or multi gated acquisition scan.

Exclusion Criteria

* Chemotherapy ≤ 21 days before first study treatment.
* Trastuzumab ≤ 21 days before first study treatment.
* Lapatinib ≤ 14 days before first study treatment.
* Prior enrollment in a trastuzumab emtansine containing study, regardless whether the patient received prior trastuzumab emtansine.
* Brain metastases that are untreated or symptomatic, or require any radiation, surgery or corticosteroid therapy to control symptoms within 1 month of randomization.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Tucson, Arizona, United States

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Hot Springs, Arkansas, United States

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Hayward, California, United States

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Highland, California, United States

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Oakland, California, United States

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Roseville, California, United States

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Sacramento, California, United States

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San Diego, California, United States

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San Francisco, California, United States

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San Jose, California, United States

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Santa Clara, California, United States

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South San Francisco, California, United States

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Stockton, California, United States

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Vallejo, California, United States

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Walnut Creek, California, United States

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West Hollywood, California, United States

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Denver, Colorado, United States

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Trumbull, Connecticut, United States

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Newark, Delaware, United States

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

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Coral Springs, Florida, United States

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Deerfield Beach, Florida, United States

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Fort Myers, Florida, United States

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Jacksonville, Florida, United States

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Plantation, Florida, United States

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Marietta, Georgia, United States

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Post Falls, Idaho, United States

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Chicago, Illinois, United States

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Chicago, Illinois, United States

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Maywood, Illinois, United States

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Fort Wayne, Indiana, United States

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Sioux City, Iowa, United States

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Wichita, Kansas, United States

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Scarborough, Maine, United States

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Bethesda, Maryland, United States

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Columbia, Maryland, United States

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Boston, Massachusetts, United States

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Boston, Massachusetts, United States

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Boston, Massachusetts, United States

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Detroit, Michigan, United States

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Minneapolis, Minnesota, United States

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St Louis, Missouri, United States

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Omaha, Nebraska, United States

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New Brunswick, New Jersey, United States

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Lake Success, New York, United States

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The Bronx, New York, United States

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Charlotte, North Carolina, United States

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Columbus, Ohio, United States

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Portland, Oregon, United States

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Philadelphia, Pennsylvania, United States

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Charleston, South Carolina, United States

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Chattanooga, Tennessee, United States

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Nashville, Tennessee, United States

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Nashville, Tennessee, United States

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Dallas, Texas, United States

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Fort Worth, Texas, United States

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San Antonio, Texas, United States

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Richmond, Virginia, United States

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Seattle, Washington, United States

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Kogarah, New South Wales, Australia

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South Brisbane, Queensland, Australia

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Frankston, Victoria, Australia

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Perth, Western Australia, Australia

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Leuven, , Belgium

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Wilrijk, , Belgium

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Salvador, Estado de Bahia, Brazil

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Goiânia, Goiás, Brazil

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Rio de Janeiro, Rio de Janeiro, Brazil

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Porto Alegre, Rio Grande do Sul, Brazil

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Itajaí, Santa Catarina, Brazil

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São Paulo, São Paulo, Brazil

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Moncton, New Brunswick, Canada

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Toronto, Ontario, Canada

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Québec, Quebec, Canada

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Regina, Saskatchewan, Canada

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Saskatoon, Saskatchewan, Canada

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Brno, , Czechia

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Hradec Králové, , Czechia

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Olomouc, , Czechia

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Prague, , Czechia

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Prague, , Czechia

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Angers, , France

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Bordeaux, , France

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Caen, , France

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Lyon, , France

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Montpellier, , France

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Nantes, , France

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Nice, , France

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Nîmes, , France

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Paris, , France

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Reims, , France

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Rouen, , France

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Saint-Priest-en-Jarez, , France

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Strasbourg, , France

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Toulouse, , France

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Toulouse, , France

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Tours, , France

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Villejuif, , France

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Bielefeld, , Germany

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Hamburg, , Germany

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Hamburg, , Germany

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Hanover, , Germany

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Kiel, , Germany

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Mainz, , Germany

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München, , Germany

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Ravensburg, , Germany

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Recklinghausen, , Germany

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Stuttgart, , Germany

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Trier, , Germany

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Troisdorf, , Germany

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Budapest, , Hungary

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Budapest, , Hungary

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Gyula, , Hungary

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Kecskemét, , Hungary

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Miskolc, , Hungary

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Szeged, , Hungary

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Szolnok, , Hungary

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Bangalore, , India

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Chennai, , India

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Kolkata, , India

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New Delhi, , India

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Pune, , India

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Pune, , India

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Beersheba, , Israel

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Hafia, , Israel

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Jerusalem, , Israel

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Petah Tikva, , Israel

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Ramat Gan, , Israel

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Rehovot, , Israel

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Tel Aviv, , Israel

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Potenza, Basilicate, Italy

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Napoli, Campania, Italy

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Genoa, Liguria, Italy

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Bergamo, Lombardy, Italy

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Brescia, Lombardy, Italy

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Milan, Lombardy, Italy

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Milan, Lombardy, Italy

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Biella, Piedmont, Italy

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Cona (Ferrara), Veneto, Italy

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Oslo, , Norway

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Bialystok, , Poland

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Bydgoszcz, , Poland

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Gdansk, , Poland

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Lublin, , Poland

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Poznan, , Poland

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Warsaw, , Poland

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Moscow, , Russia

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Samara, , Russia

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Stavropol, , Russia

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Košice, , Slovakia

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Poprad, , Slovakia

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Kyunggi-do, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Barcelona, Barcelona, Spain

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Barcelona, Barcelona, Spain

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A Coruña, La Coruña, Spain

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Madrid, Madrid, Spain

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Madrid, Madrid, Spain

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Madrid, Madrid, Spain

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Málaga, Malaga, Spain

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Murcia, Murcia, Spain

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Seville, Sevilla, Spain

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Valencia, Valencia, Spain

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Bilbao, Vizcaya, Spain

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Örebro, , Sweden

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Umeå, , Sweden

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Uppsala, , Sweden

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Bern, , Switzerland

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Zurich, , Switzerland

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Bangkok, , Thailand

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Bangkok, , Thailand

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Bangkok, , Thailand

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Brighton, , United Kingdom

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Guildford, , United Kingdom

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London, , United Kingdom

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Maidstone, , United Kingdom

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Metropolitan Borough of Wirral, , United Kingdom

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Nottingham, , United Kingdom

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Sheffield, , United Kingdom

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Stoke-on-Trent, , United Kingdom

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Westcliffe-on-sea, , United Kingdom

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Countries

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United States Australia Belgium Brazil Canada Czechia France Germany Hungary India Israel Italy Norway Poland Russia Slovakia South Korea Spain Sweden Switzerland Thailand United Kingdom

References

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Chen SC, Quartino A, Polhamus D, Riggs M, French J, Wang X, Vadhavkar S, Smitt M, Hoersch S, Strasak A, Jin JY, Girish S, Li C. Population pharmacokinetics and exposure-response of trastuzumab emtansine in advanced breast cancer previously treated with >/=2 HER2-targeted regimens. Br J Clin Pharmacol. 2017 Dec;83(12):2767-2777. doi: 10.1111/bcp.13381. Epub 2017 Sep 3.

Reference Type DERIVED
PMID: 28733983 (View on PubMed)

Krop IE, Kim SB, Martin AG, LoRusso PM, Ferrero JM, Badovinac-Crnjevic T, Hoersch S, Smitt M, Wildiers H. Trastuzumab emtansine versus treatment of physician's choice in patients with previously treated HER2-positive metastatic breast cancer (TH3RESA): final overall survival results from a randomised open-label phase 3 trial. Lancet Oncol. 2017 Jun;18(6):743-754. doi: 10.1016/S1470-2045(17)30313-3. Epub 2017 May 16.

Reference Type DERIVED
PMID: 28526538 (View on PubMed)

Krop IE, Kim SB, Gonzalez-Martin A, LoRusso PM, Ferrero JM, Smitt M, Yu R, Leung AC, Wildiers H; TH3RESA study collaborators. Trastuzumab emtansine versus treatment of physician's choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014 Jun;15(7):689-99. doi: 10.1016/S1470-2045(14)70178-0. Epub 2014 May 2.

Reference Type DERIVED
PMID: 24793816 (View on PubMed)

Other Identifiers

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BO25734

Identifier Type: OTHER

Identifier Source: secondary_id

2011-000509-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

TDM4997g

Identifier Type: -

Identifier Source: org_study_id

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