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Breast CancerPhase 3TH3RESANCT01419197

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

A Phase 3 study testing Trastuzumab emtansine and Treatment of physician's choice in people with Breast Cancer, run by Hoffmann-La Roche at 184 sites in 22 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer
What is being tested?
Trastuzumab emtansine and Treatment of physician's choice
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
602 participants
Where
184 sitesin 22 countries
Study dates
Sep 2011to Aug 2015
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 10Show fewer
  • 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.

Who cannot join

  • 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.

Trial locations and contacts

184 sites in 22 countries.

184 sites in 22 countries

United States59 sites

  • Study site

    Bethesda, Maryland, 20817

  • Study site

    Boston, Massachusetts, 02115

  • Study site

    Boston, Massachusetts, 02130

  • Study site

    Boston, Massachusetts, 02215

  • Study site

    Charleston, South Carolina, 29414

  • Study site

    Charlotte, North Carolina, 28203

  • Study site

    Chattanooga, Tennessee, 37404

  • Study site

    Chicago, Illinois, 60612

  • Study site

    Chicago, Illinois, 60637

  • Study site

    Columbia, Maryland, 21044

  • Study site

    Columbus, Ohio, 43219

  • Study site

    Coral Springs, Florida, 33065

  • Study site

    Dallas, Texas, 75246

  • Study site

    Deerfield Beach, Florida, 33442

  • Study site

    Denver, Colorado, 80220

  • Study site

    Detroit, Michigan, 48201

  • Study site

    Fort Myers, Florida, 33905

  • Study site

    Fort Wayne, Indiana, 46815

  • Study site

    Fort Worth, Texas, 76104

  • Study site

    Hayward, California, 94545

  • Study site

    Highland, California, 92346

  • Study site

    Hot Springs, Arkansas, 71913

  • Study site

    Jacksonville, Florida, 32256

  • Study site

    Lake Success, New York, 11042

  • Study site

    Marietta, Georgia, 30060

  • Study site

    Maywood, Illinois, 60153

  • Study site

    Minneapolis, Minnesota, 55455

  • Study site

    Nashville, Tennessee, 37203

  • Study site

    Nashville, Tennessee, 37232

  • Study site

    New Brunswick, New Jersey, 08901

  • Study site

    Newark, Delaware, 19713

  • Study site

    Oakland, California, 94611

  • Study site

    Omaha, Nebraska, 68114

  • Study site

    Philadelphia, Pennsylvania, 19104

  • Study site

    Plantation, Florida, 33324

  • Study site

    Portland, Oregon, 97210

  • Study site

    Post Falls, Idaho, 83854

  • Study site

    Richmond, Virginia, 23230

  • Study site

    Roseville, California, 95661

  • Study site

    Sacramento, California, 95825

  • Study site

    San Antonio, Texas, 78229

  • Study site

    San Diego, California, 92108

  • Study site

    San Francisco, California, 94115

  • Study site

    San Jose, California, 95119

  • Study site

    Santa Clara, California, 95051

  • Study site

    Scarborough, Maine, 04074

  • Study site

    Seattle, Washington, 98109

  • Study site

    Sioux City, Iowa, 51101

  • Study site

    South San Francisco, California, 94080

  • Study site

    St Louis, Missouri, 63141

  • Study site

    Stockton, California, 95204

  • Study site

    The Bronx, New York, 10467

  • Study site

    Trumbull, Connecticut, 06611

  • Study site

    Tucson, Arizona, 85704

  • Study site

    Vallejo, California, 94589

  • Study site

    Walnut Creek, California, 94596

  • Study site

    Washington D.C., District of Columbia, 20010

  • Study site

    West Hollywood, California, 90048

  • Study site

    Wichita, Kansas, 67214-3728

Other trials in United States

France17 sites

  • Study site

    Angers, 49933

  • Study site

    Bordeaux, 33300

  • Study site

    Caen, 14076

  • Study site

    Lyon, 69373

  • Study site

    Montpellier, 34298

  • Study site

    Nantes, 44202

  • Study site

    Nice, 06189

  • Study site

    Nîmes, 30900

  • Study site

    Paris, 75231

  • Study site

    Reims, 51056

  • Study site

    Rouen, 76038

  • Study site

    Saint-Priest-en-Jarez, 42271

  • Study site

    Strasbourg, 67065

  • Study site

    Toulouse, 31059

  • Study site

    Toulouse, 31300

  • Study site

    Tours, 37044

  • Study site

    Villejuif, 94800

Other trials in France

Germany12 sites

  • Study site

    Bielefeld, 33604

  • Study site

    Hamburg, 20246

  • Study site

    Hamburg, 22081

  • Study site

    Hanover, 30559

  • Study site

    Kiel, 24105

  • Study site

    Mainz, 55131

  • Study site

    München, 80638

  • Study site

    Ravensburg, 88212

  • Study site

    Recklinghausen, 45657

  • Study site

    Stuttgart, 70190

  • Study site

    Trier, 54290

  • Study site

    Troisdorf, 53840

Other trials in Germany

Spain11 sites

  • Study site

    A Coruña, La Coruña, 15009

  • Study site

    Barcelona, Barcelona, 08036

  • Study site

    Barcelona, Barcelona, 08907

  • Study site

    Bilbao, Vizcaya, 48013

  • Study site

    Madrid, Madrid, 28033

  • Study site

    Madrid, Madrid, 28034

  • Study site

    Madrid, Madrid, 28040

  • Study site

    Málaga, Malaga, 29010

  • Study site

    Murcia, Murcia, 30008

  • Study site

    Seville, Sevilla, 41014

  • Study site

    Valencia, Valencia, 46026

Other trials in Spain

Italy9 sites

  • Study site

    Bergamo, Lombardy, 24127

  • Study site

    Biella, Piedmont, 13900

  • Study site

    Brescia, Lombardy, 25123

  • Study site

    Cona (Ferrara), Veneto, 44124

  • Study site

    Genoa, Liguria, 16132

  • Study site

    Milan, Lombardy, 20121

  • Study site

    Milan, Lombardy, 20132

  • Study site

    Naples, Campania, 80131

  • Study site

    Potenza, Basilicate, 85100

Other trials in Italy

United Kingdom9 sites

  • Study site

    Brighton, BN2 5BE

  • Study site

    Guildford, GU2 7XX

  • Study site

    London, W1G 6AD

  • Study site

    Maidstone, ME16 9QQ

  • Study site

    Metropolitan Borough of Wirral, L63 4JY

  • Study site

    Nottingham, NG5 1PB

  • Study site

    Sheffield, S10 2SJ

  • Study site

    Stoke-on-Trent, ST4 6QG

  • Study site

    Westcliffe-on-sea, SS0 0RY

Other trials in United Kingdom

Hungary7 sites

  • Study site

    Budapest, 1122

  • Study site

    Budapest, 1145

  • Study site

    Gyula, 5700

  • Study site

    Kecskemét, 6000

  • Study site

    Miskolc, 3526

  • Study site

    Szeged, 6701

  • Study site

    Szolnok, 5004

Other trials in Hungary

Israel7 sites

  • Study site

    Beersheba, 8410101

  • Study site

    Hafia, 3109601

  • Study site

    Jerusalem, 91120

  • Study site

    Petah Tikva, 49100

  • Study site

    Ramat Gan, 52621

  • Study site

    Rehovot, 7610001

  • Study site

    Tel Aviv, 6423906

Other trials in Israel

Brazil6 sites

  • Study site

    Goiânia, Goiás, 74140-050

  • Study site

    Itajaí, Santa Catarina, 88301-220

  • Study site

    Porto Alegre, Rio Grande do Sul, 90430-090

  • Study site

    Rio de Janeiro, Rio de Janeiro, 22260-020

  • Study site

    Salvador, Estado de Bahia, 41950-610

  • Study site

    São Paulo, São Paulo, 01509-900

Other trials in Brazil

India6 sites

  • Study site

    Bangalore, 560027

  • Study site

    Chennai, 600035

  • Study site

    Kolkata, 700053

  • Study site

    New Delhi, 110085

  • Study site

    Pune, 411 001

  • Study site

    Pune, 411004

Other trials in India

Poland6 sites

  • Study site

    Bialystok, 15-027

  • Study site

    Bydgoszcz, 85-796

  • Study site

    Gdansk, 80-952

  • Study site

    Lublin, 20-090

  • Study site

    Poznan, 61-866

  • Study site

    Warsaw, 02-781

Other trials in Poland

Canada5 sites

  • Study site

    Moncton, New Brunswick, E1C 6Z8

  • Study site

    Québec, Quebec, G1S 4L8

  • Study site

    Regina, Saskatchewan, S4T 7T1

  • Study site

    Saskatoon, Saskatchewan, S7N 4H4

  • Study site

    Toronto, Ontario, M4N 3M5

Other trials in Canada

Czechia5 sites

  • Study site

    Brno, 656 53

  • Study site

    Hradec Králové, 500 05

  • Study site

    Olomouc, 775 20

  • Study site

    Prague, 128 08

  • Study site

    Prague, 150 06

Other trials in Czechia

South Korea5 sites

  • Study site

    Kyunggi-do, 410-769

  • Study site

    Seoul, 110-744

  • Study site

    Seoul, 120-752

  • Study site

    Seoul, 135-170

  • Study site

    Seoul, 138-736

Other trials in South Korea

Australia4 sites

  • Study site

    Frankston, Victoria, 3199

  • Study site

    Kogarah, New South Wales, 2217

  • Study site

    Perth, Western Australia, 6000

  • Study site

    South Brisbane, Queensland, 4101

Other trials in Australia

Russia3 sites

  • Study site

    Moscow, 115478

  • Study site

    Samara, 443031

  • Study site

    Stavropol, 355045

Other trials in Russia

Sweden3 sites

  • Study site

    Örebro, 701 85

  • Study site

    Umeå, 90185

  • Study site

    Uppsala, 75185

Other trials in Sweden

Thailand3 sites

  • Study site

    Bangkok, 10110

  • Study site

    Bangkok, 10400

  • Study site

    Bangkok, 10700

Other trials in Thailand

Belgium2 sites

  • Study site

    Leuven, 3000

  • Study site

    Wilrijk, 2610

Other trials in Belgium

Slovakia2 sites

  • Study site

    Košice, 04001

  • Study site

    Poprad, 058 01

Other trials in Slovakia

Switzerland2 sites

  • Study site

    Bern, 3010

  • Study site

    Zurich, 8091

Other trials in Switzerland

Norway1 site

  • Study site

    Oslo, 0310

Other trials in Norway

About this study

Official title: 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.

Conditions
Breast Cancer
Being tested
Trastuzumab emtansine, Treatment of physician's choice
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Trastuzumab emtansineDrug

    Also called Kadcyla, T-DM1

    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 choiceDrug

    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.

Study groups in NCT01419197
Study groupRoleWhat they receive
Trastuzumab emtansineExperimentalTrastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
Receives: Drug: Trastuzumab emtansine
Treatment of physician's choiceActive comparatorTreatment 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.
Receives: Drug: Treatment of physician's choice

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. Overall Survival

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

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

Secondary outcomes (7)

  1. Percentage of Participants With an Objective Response

    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.

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

  2. Duration of the Objective Response

    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.

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

  3. 6-month and 1-year Survival

    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.

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

  4. Time to Pain Symptom Progression

    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.

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

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

    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.

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

  6. Overall Survival (Final Analysis)

    Overall survival was defined as the time from randomization to death from any cause.

    Measured: Baseline to the clinical cut-off date of 13 Feb 2015 (up to 4 years)

  7. 6-month and 1-year Survival (Final Analysis)

    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.

    Measured: Baseline to the clinical cut-off date of 13 Feb 2015 (up to 4 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Aug 2011 (estimated)
  2. Study startSep 2011
  3. Primary completionFeb 2013
  4. Study completionAug 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
602 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01419197
Sponsor's protocol ID
TDM4997g
Other IDs
BO25734, 2011-000509-29
Acronym
TH3RESA
Status last verified
Aug 2016
First submitted
16 Aug 2011
Last updated
12 Oct 2016

Publications

  • 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.

    PubMed 28733983

  • 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.

    PubMed 28526538

  • 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.

    PubMed 24793816

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Trastuzumab emtansine and Treatment of physician's choice in people with Breast Cancer, run by Hoffmann-La Roche at 184 sites in 22 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 184 sites in United States, France, Germany, Spain, Italy and 17 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (time frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01419197, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2016.

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