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 (TH3RESA)

August 17, 2016 updated by: Hoffmann-La Roche

A Phase III Randomized, Multicenter, Two Arm, Open-label Trial to Evaluate the Efficacy of Trastuzumab Emtansine Compared With Treatment of Physician's Choice in Patients With HER2-positive Metastatic Breast Cancer Who Have Received at Least Two Prior Regimens of HER2 Directed Therapy

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

602

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Kogarah, New South Wales, Australia, 2217
    • Queensland
      • South Brisbane, Queensland, Australia, 4101
    • Victoria
      • Frankston, Victoria, Australia, 3199
    • Western Australia
      • Perth, Western Australia, Australia, 6000
  • Belgium
      • Leuven, Belgium, 3000
      • Wilrijk, Belgium, 2610
  • Brazil
    • BA
      • Salvador, BA, Brazil, 41950-610
    • GO
      • Goiania, GO, Brazil, 74140-050
    • RJ
      • Rio de Janeiro, RJ, Brazil, 22260-020
    • RS
      • Porto Alegre, RS, Brazil, 90430-090
    • SC
      • Itajai, SC, Brazil, 88301-220
    • SP
      • Sao Paulo, SP, Brazil, 01509-900
  • Canada
      • Quebec, Canada, G1S 4L8
    • New Brunswick
      • Moncton, New Brunswick, Canada, E1C 6Z8
    • Ontario
      • Toronto, Ontario, Canada, M4N 3M5
    • Saskatchewan
      • Regina, Saskatchewan, Canada, S4T 7T1
      • Saskatoon, Saskatchewan, Canada, S7N 4H4
  • Czech Republic
      • Brno, Czech Republic, 656 53
      • Hradec Kralove, Czech Republic, 500 05
      • Olomouc, Czech Republic, 775 20
      • Praha 2, Czech Republic, 128 08
      • Praha 5, Czech Republic, 150 06
  • France
      • Angers, France, 49933
      • Bordeaux, France, 33300
      • Caen, France, 14076
      • Lyon, France, 69373
      • Montpellier cedex 5, France, 34298
      • Nantes, France, 44202
      • Nice, France, 06189
      • Nimes, France, 30900
      • Paris, France, 75231
      • Reims CEDEX, France, 51056
      • Rouen, France, 76038
      • St-Priest-En-Jarez, France, 42271
      • Strasbourg, France, 67065
      • Toulouse, France, 31059
      • Toulouse, France, 31300
      • Tours, France, 37044
      • Villejuif, France, 94800
  • Germany
      • Bielefeld, Germany, 33604
      • Hamburg, Germany, 22081
      • Hamburg, Germany, 20246
      • Hannover, Germany, 30559
      • Kiel, Germany, 24105
      • Mainz, Germany, 55131
      • München, Germany, 80638
      • Ravensburg, Germany, 88212
      • Recklinghausen, Germany, 45657
      • Stuttgart, Germany, 70190
      • Trier, Germany, 54290
      • Troisdorf, Germany, 53840
  • Hungary
      • Budapest, Hungary, 1122
      • Budapest, Hungary, 1145
      • Gyula, Hungary, 5700
      • Kecskemet, Hungary, 6000
      • Miskolc, Hungary, 3526
      • Szeged, Hungary, 6701
      • Szolnok, Hungary, 5004
  • India
      • Bangalore, India, 560027
      • Chennai, India, 600035
      • Kolkata, India, 700053
      • New Delhi, India, 110085
      • Pune, India, 411004
      • Pune, India, 411 001
  • Israel
      • Beer Sheva, Israel, 8410101
      • Hafia, Israel, 3109601
      • Jerusalem, Israel, 91120
      • Petach Tikva, Israel, 49100
      • Ramat-Gan, Israel, 52621
      • Rehovot, Israel, 7610001
      • Tel Aviv, Israel, 6423906
  • Italy
    • Basilicata
      • Potenza, Basilicata, Italy, 85100
    • Campania
      • Napoli, Campania, Italy, 80131
    • Liguria
      • Genova, Liguria, Italy, 16132
    • Lombardia
      • Bergamo, Lombardia, Italy, 24127
      • Brescia, Lombardia, Italy, 25123
      • Milano, Lombardia, Italy, 20132
      • Milano, Lombardia, Italy, 20121
    • Piemonte
      • Biella, Piemonte, Italy, 13900
    • Veneto
      • Cona (Ferrara), Veneto, Italy, 44124
  • Korea, Republic of
      • Kyunggi-do, Korea, Republic of, 410-769
      • Seoul, Korea, Republic of, 138-736
      • Seoul, Korea, Republic of, 110-744
      • Seoul, Korea, Republic of, 120-752
      • Seoul, Korea, Republic of, 135-170
  • Norway
      • Oslo, Norway, 0310
  • Poland
      • Bialystok, Poland, 15-027
      • Bydgoszcz, Poland, 85-796
      • Gdansk, Poland, 80-952
      • Lublin, Poland, 20-090
      • Poznan, Poland, 61-866
      • Warszawa, Poland, 02-781
  • Russian Federation
      • Moscow, Russian Federation, 115478
      • Samara, Russian Federation, 443031
      • Stavropol, Russian Federation, 355045
  • Slovakia
      • Kosice, Slovakia, 04001
      • Poprad, Slovakia, 058 01
  • Spain
      • Barcelona, Spain, 08036
      • Barcelona, Spain, 08907
      • Madrid, Spain, 28040
      • Madrid, Spain, 28034
      • Madrid, Spain, 28033
      • Malaga, Spain, 29010
      • Murcia, Spain, 30008
      • Sevilla, Spain, 41014
      • Valencia, Spain, 46026
    • La Coruña
      • La Coruna, La Coruña, Spain, 15009
    • Vizcaya
      • Bilbao, Vizcaya, Spain, 48013
  • Sweden
      • Umea, Sweden, 90185
      • Uppsala, Sweden, 75185
      • Örebro, Sweden, 701 85
  • Switzerland
      • Bern, Switzerland, 3010
      • Zürich, Switzerland, 8091
  • Thailand
      • Bangkok, Thailand, 10400
      • Bangkok, Thailand, 10700
      • Bangkok, Thailand, 10110
  • United Kingdom
      • Brighton, United Kingdom, BN2 5BE
      • Guildford, United Kingdom, GU2 7XX
      • London, United Kingdom, W1G 6AD
      • Maidstone, United Kingdom, ME16 9QQ
      • Nottingham, United Kingdom, NG5 1PB
      • Sheffield, United Kingdom, S10 2SJ
      • Stoke-on-Trent, United Kingdom, ST4 6QG
      • Westcliffe-on-sea, United Kingdom, SS0 0RY
      • Wirral, United Kingdom, L63 4JY
  • United States
    • Arizona
      • Tucson, Arizona, United States, 85704
    • Arkansas
      • Hot Springs, Arkansas, United States, 71913
    • California
      • Hayward, California, United States, 94545
      • Highland, California, United States, 92346
      • Oakland, California, United States, 94611
      • Roseville, California, United States, 95661
      • Sacramento, California, United States, 95825
      • San Diego, California, United States, 92108
      • San Francisco, California, United States, 94115
      • San Jose, California, United States, 95119
      • Santa Clara, California, United States, 95051
      • South San Francisco, California, United States, 94080
      • Stockton, California, United States, 95204
      • Vallejo, California, United States, 94589
      • Walnut Creek, California, United States, 94596
      • West Hollywood, California, United States, 90048
    • Colorado
      • Denver, Colorado, United States, 80220
    • Connecticut
      • Trumbull, Connecticut, United States, 06611
    • Delaware
      • Newark, Delaware, United States, 19713
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
    • Florida
      • Coral Springs, Florida, United States, 33065
      • Deerfield Beach, Florida, United States, 33442
      • Fort Myers, Florida, United States, 33905
      • Jacksonville, Florida, United States, 32256
      • Plantation, Florida, United States, 33324
    • Georgia
      • Marietta, Georgia, United States, 30060
    • Idaho
      • Post Falls, Idaho, United States, 83854
    • Illinois
      • Chicago, Illinois, United States, 60637
      • Chicago, Illinois, United States, 60612
      • Maywood, Illinois, United States, 60153
    • Indiana
      • Fort Wayne, Indiana, United States, 46815
    • Iowa
      • Sioux City, Iowa, United States, 51101
    • Kansas
      • Wichita, Kansas, United States, 67214-3728
    • Maine
      • Scarborough, Maine, United States, 04074
    • Maryland
      • Bethesda, Maryland, United States, 20817
      • Columbia, Maryland, United States, 21044
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
      • Boston, Massachusetts, United States, 02115
      • Boston, Massachusetts, United States, 02130
    • Michigan
      • Detroit, Michigan, United States, 48201
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
    • Missouri
      • Saint Louis, Missouri, United States, 63141
    • Nebraska
      • Omaha, Nebraska, United States, 68114
    • New Jersey
      • New Brunswick, New Jersey, United States, 08901
    • New York
      • Bronx, New York, United States, 10467
      • Lake Success, New York, United States, 11042
    • North Carolina
      • Charlotte, North Carolina, United States, 28203
    • Ohio
      • Columbus, Ohio, United States, 43219
    • Oregon
      • Portland, Oregon, United States, 97210
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
    • South Carolina
      • Charleston, South Carolina, United States, 29414
    • Tennessee
      • Chattanooga, Tennessee, United States, 37404
      • Nashville, Tennessee, United States, 37232
      • Nashville, Tennessee, United States, 37203
    • Texas
      • Dallas, Texas, United States, 75246
      • Fort Worth, Texas, United States, 76104
      • San Antonio, Texas, United States, 78229
    • Virginia
      • Richmond, Virginia, United States, 23230
    • Washington
      • Seattle, Washington, United States, 98109

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Trastuzumab emtansine
Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
Drug: 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.
Other Names:
  • Kadcyla
  • T-DM1
Active Comparator: 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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival
Time Frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
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
Time Frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With an Objective Response
Time Frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
An objective response was defined as a complete or partial response determined on 2 consecutive occasions ≥ 4 weeks apart using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete response was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must be < 10 mm on the short axis. Partial response was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum. Participants who had no post-baseline tumor assessment were counted as non-responders.
Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Duration of the Objective Response
Time Frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Duration of the objective response was defined as the time from the first tumor assessment that was judged to indicate that the patient had an objective response to the time of first documented disease progression using RECIST v1.1 per investigator assessment or death from any cause, whichever occurred first.
Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
6-month and 1-year Survival
Time Frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
6-month and 1-year survival were defined as the percentage of participants who were alive at 6 months and 1 year, respectively, as estimated using Kaplan-Meier method.
Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Time to Pain Symptom Progression
Time Frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Time to pain symptom progression was defined as the time from randomization to the first documentation of an increase in narcotic use and/or a 10 point increase from Baseline in the pain score as measured by the European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire for patients with bone metastases (EORTC QLQ-BM22). The EORTC QLQ-BM22 assesses the symptoms of bone metastases using 22 items: 5 items for sites of pain, 3 pain characteristics, 8 functional interference aspects, and 6 psychosocial aspects. The pain score was derived from the 3 pain characteristic items. Each item was rated on a 4-point scale, where 1=Not at all to 4=Very much. The pain score was the sum of the 3 pain characteristic scores and was normalized to a scale of 0 to 100. A higher score indicates greater pain.
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
Time Frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
The EORTC QLQ-BM22 assesses the symptoms of bone metastases using 22 items: 5 items for sites of pain, 3 pain characteristics, 8 functional interference aspects, and 6 psychosocial aspects. The pain score was derived from the 3 pain characteristic items. Each item was rated on a 4-point scale, where 1=Not at all to 4=Very much. The pain score was the sum of the 3 pain characteristic scores and was normalized to a scale of 0 to 100. A higher score indicates greater pain. A negative change score indicates improvement.
Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Overall Survival (Final Analysis)
Time Frame: Baseline to the clinical cut-off date of 13 Feb 2015 (up to 4 years)
Overall survival was defined as the time from randomization to death from any cause.
Baseline to the clinical cut-off date of 13 Feb 2015 (up to 4 years)
6-month and 1-year Survival (Final Analysis)
Time Frame: Baseline to the clinical cut-off date of 13 Feb 2015 (up to 4 years)
6-month and 1-year survival were defined as the percentage of participants who were alive at 6 months and 1 year, respectively, as estimated using Kaplan-Meier method.
Baseline to the clinical cut-off date of 13 Feb 2015 (up to 4 years)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hoffmann-La Roche

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2011

Primary Completion (Actual)

February 1, 2013

Study Completion (Actual)

August 1, 2015

Study Registration Dates

First Submitted

August 16, 2011

First Submitted That Met QC Criteria

August 16, 2011

First Posted (Estimate)

August 18, 2011

Study Record Updates

Last Update Posted (Estimate)

October 12, 2016

Last Update Submitted That Met QC Criteria

August 17, 2016

Last Verified

August 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TDM4997g
  • BO25734 (Other Identifier: Hoffmann-La Roche)
  • 2011-000509-29 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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