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

NCT01419197 | Completed Phase 3 Results

• 3 other identifiers: TDM4997gBO257342011-000509-29
• Study Type: interventional
• Target: 602
• Locations: 22 countries
• Sites: 184

Brief Summary

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Progression-free Survival

  Progression-free survival was defined as the time from randomization to the first documented disease progression by investigator assessment using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 or death from any cause, whichever occurred first. Progression-free survival was a co-primary endpoint.

  Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)

• Overall Survival

  Overall survival (OS) was defined as the time from randomization to death from any cause. Overall survival was a co-primary endpoint.

  Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)

Secondary Outcomes (7)

• Percentage of Participants With an Objective Response

  Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)

• Duration of the Objective Response

  Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)

• 6-month and 1-year Survival

  Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)

• Time to Pain Symptom Progression

  Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)

• Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle

  Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)

Study Arms (2)

Trastuzumab emtansine

EXPERIMENTAL

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

Drug: Trastuzumab emtansine

Treatment of physician's choice

ACTIVE COMPARATOR

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.

Drug: Treatment of physician's choice

Interventions

Trastuzumab emtansine 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.

Also known as: Kadcyla, T-DM1

Trastuzumab emtansine

Treatment of physician's choice 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.

Treatment of physician's choice

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (184)

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Tucson, Arizona, 85704, United States

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Hot Springs, Arkansas, 71913, United States

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Hayward, California, 94545, United States

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Highland, California, 92346, United States

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Oakland, California, 94611, United States

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Roseville, California, 95661, United States

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Sacramento, California, 95825, United States

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San Diego, California, 92108, United States

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San Francisco, California, 94115, United States

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San Jose, California, 95119, United States

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Santa Clara, California, 95051, United States

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South San Francisco, California, 94080, United States

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Stockton, California, 95204, United States

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Vallejo, California, 94589, United States

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Walnut Creek, California, 94596, United States

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West Hollywood, California, 90048, United States

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Denver, Colorado, 80220, United States

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Trumbull, Connecticut, 06611, United States

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Newark, Delaware, 19713, United States

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Washington D.C., District of Columbia, 20010, United States

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Coral Springs, Florida, 33065, United States

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Deerfield Beach, Florida, 33442, United States

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Fort Myers, Florida, 33905, United States

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Jacksonville, Florida, 32256, United States

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Plantation, Florida, 33324, United States

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Marietta, Georgia, 30060, United States

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Post Falls, Idaho, 83854, United States

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Chicago, Illinois, 60612, United States

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Chicago, Illinois, 60637, United States

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Maywood, Illinois, 60153, United States

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Fort Wayne, Indiana, 46815, United States

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Sioux City, Iowa, 51101, United States

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Wichita, Kansas, 67214-3728, United States

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Scarborough, Maine, 04074, United States

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Bethesda, Maryland, 20817, United States

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Columbia, Maryland, 21044, United States

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Boston, Massachusetts, 02115, United States

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Boston, Massachusetts, 02130, United States

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Boston, Massachusetts, 02215, United States

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Detroit, Michigan, 48201, United States

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Minneapolis, Minnesota, 55455, United States

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St Louis, Missouri, 63141, United States

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Omaha, Nebraska, 68114, United States

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New Brunswick, New Jersey, 08901, United States

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Lake Success, New York, 11042, United States

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The Bronx, New York, 10467, United States

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Charlotte, North Carolina, 28203, United States

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Columbus, Ohio, 43219, United States

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Portland, Oregon, 97210, United States

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Philadelphia, Pennsylvania, 19104, United States

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Charleston, South Carolina, 29414, United States

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Chattanooga, Tennessee, 37404, United States

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Nashville, Tennessee, 37203, United States

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Nashville, Tennessee, 37232, United States

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Dallas, Texas, 75246, United States

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Fort Worth, Texas, 76104, United States

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San Antonio, Texas, 78229, United States

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Richmond, Virginia, 23230, United States

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Seattle, Washington, 98109, United States

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Kogarah, New South Wales, 2217, Australia

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South Brisbane, Queensland, 4101, Australia

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Frankston, Victoria, 3199, Australia

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Perth, Western Australia, 6000, Australia

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Leuven, 3000, Belgium

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Wilrijk, 2610, Belgium

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Salvador, Estado de Bahia, 41950-610, Brazil

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Goiânia, Goiás, 74140-050, Brazil

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Rio de Janeiro, Rio de Janeiro, 22260-020, Brazil

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Porto Alegre, Rio Grande do Sul, 90430-090, Brazil

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Itajaí, Santa Catarina, 88301-220, Brazil

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São Paulo, São Paulo, 01509-900, Brazil

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Moncton, New Brunswick, E1C 6Z8, Canada

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Toronto, Ontario, M4N 3M5, Canada

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Québec, Quebec, G1S 4L8, Canada

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Regina, Saskatchewan, S4T 7T1, Canada

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Saskatoon, Saskatchewan, S7N 4H4, Canada

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Brno, 656 53, Czechia

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Hradec Králové, 500 05, Czechia

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Olomouc, 775 20, Czechia

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Prague, 128 08, Czechia

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Prague, 150 06, Czechia

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Angers, 49933, France

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Bordeaux, 33300, France

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Caen, 14076, France

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Lyon, 69373, France

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Montpellier, 34298, France

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Nantes, 44202, France

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Nice, 06189, France

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Nîmes, 30900, France

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Paris, 75231, France

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Reims, 51056, France

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Rouen, 76038, France

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Saint-Priest-en-Jarez, 42271, France

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Strasbourg, 67065, France

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Toulouse, 31059, France

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Toulouse, 31300, France

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Tours, 37044, France

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Villejuif, 94800, France

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Bielefeld, 33604, Germany

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Hamburg, 20246, Germany

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Hamburg, 22081, Germany

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Hanover, 30559, Germany

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Kiel, 24105, Germany

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Mainz, 55131, Germany

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München, 80638, Germany

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Ravensburg, 88212, Germany

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Recklinghausen, 45657, Germany

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Stuttgart, 70190, Germany

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Trier, 54290, Germany

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Troisdorf, 53840, Germany

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Budapest, 1122, Hungary

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Budapest, 1145, Hungary

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Gyula, 5700, Hungary

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Kecskemét, 6000, Hungary

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Miskolc, 3526, Hungary

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Szeged, 6701, Hungary

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Szolnok, 5004, Hungary

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Bangalore, 560027, India

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Chennai, 600035, India

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Kolkata, 700053, India

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New Delhi, 110085, India

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Pune, 411 001, India

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Pune, 411004, India

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Beersheba, 8410101, Israel

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Hafia, 3109601, Israel

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Jerusalem, 91120, Israel

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Petah Tikva, 49100, Israel

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Ramat Gan, 52621, Israel

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Rehovot, 7610001, Israel

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Tel Aviv, 6423906, Israel

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Potenza, Basilicate, 85100, Italy

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Napoli, Campania, 80131, Italy

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Genoa, Liguria, 16132, Italy

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Bergamo, Lombardy, 24127, Italy

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Brescia, Lombardy, 25123, Italy

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Milan, Lombardy, 20121, Italy

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Milan, Lombardy, 20132, Italy

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Biella, Piedmont, 13900, Italy

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Cona (Ferrara), Veneto, 44124, Italy

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Oslo, 0310, Norway

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Bialystok, 15-027, Poland

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Bydgoszcz, 85-796, Poland

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Gdansk, 80-952, Poland

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Lublin, 20-090, Poland

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Poznan, 61-866, Poland

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Warsaw, 02-781, Poland

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Moscow, 115478, Russia

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Samara, 443031, Russia

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Stavropol, 355045, Russia

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Košice, 04001, Slovakia

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Poprad, 058 01, Slovakia

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Kyunggi-do, 410-769, South Korea

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Seoul, 110-744, South Korea

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Seoul, 120-752, South Korea

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Seoul, 135-170, South Korea

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Seoul, 138-736, South Korea

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Barcelona, Barcelona, 08036, Spain

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Barcelona, Barcelona, 08907, Spain

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A Coruña, La Coruña, 15009, Spain

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Madrid, Madrid, 28033, Spain

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Madrid, Madrid, 28034, Spain

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Madrid, Madrid, 28040, Spain

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Málaga, Malaga, 29010, Spain

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Murcia, Murcia, 30008, Spain

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Seville, Sevilla, 41014, Spain

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Valencia, Valencia, 46026, Spain

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Bilbao, Vizcaya, 48013, Spain

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Örebro, 701 85, Sweden

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Umeå, 90185, Sweden

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Uppsala, 75185, Sweden

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Bern, 3010, Switzerland

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Zurich, 8091, Switzerland

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Bangkok, 10110, Thailand

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Bangkok, 10400, Thailand

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Bangkok, 10700, Thailand

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Brighton, BN2 5BE, United Kingdom

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Guildford, GU2 7XX, United Kingdom

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London, W1G 6AD, United Kingdom

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Maidstone, ME16 9QQ, United Kingdom

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Metropolitan Borough of Wirral, L63 4JY, United Kingdom

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Nottingham, NG5 1PB, United Kingdom

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Sheffield, S10 2SJ, United Kingdom

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Stoke-on-Trent, ST4 6QG, United Kingdom

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Westcliffe-on-sea, SS0 0RY, United Kingdom

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Related Publications (3)

• 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.

  PMID: 28733983 DERIVED

• 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.

  PMID: 28526538 DERIVED

• 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.

  PMID: 24793816 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Ado-Trastuzumab Emtansine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Trastuzumab; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2011
• First Posted: August 18, 2011
• Study Start: September 1, 2011
• Primary Completion: February 1, 2013
• Study Completion: August 1, 2015
• Last Updated: October 12, 2016
• Results First Posted: May 5, 2014

Record last verified: 2016-08

Locations

FR (17); US (59); SE (3); GB (9); NO (1); ES (11); RU (3); KR (5); PL (6); IL (7); CZ (5); TH (3); HU (7); IT (9); AU (4); BE (2); IN (6); DE (12); SL (2); CA (5); CH (2); BR (6)