A Study of Trastuzumab Emtansine in Comparison With Treatment of Physician's Choice in Patients With HER2-positive Breast Cancer Who Have Received at Least Two Prior Regimens of HER2-directed Therapy (TH3RESA)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01419197
First received: August 16, 2011
Last updated: April 3, 2014
Last verified: April 2014
  Purpose

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 patients with metastatic or unresectable locally advanced/recurrent HER2-positive breast cancer. Eligible patients will be randomized to receive either trastuzumab emtansine 3.6 mg/kg intravenously every 21 days or treatment of the physician's choice. Patients continue to receive study treatment until disease progression or unacceptable toxicity occurs. This study is also known under Roche study protocol number BO25734.


Condition Intervention Phase
Breast Cancer
Drug: Trastuzumab emtansine
Drug: Treatment of physician's choice
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Progression-free Survival [ Time Frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years) ] [ Designated as safety issue: No ]
    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.

  • Overall Survival [ Time Frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years) ] [ Designated as safety issue: No ]
    Overall survival was defined as the time from randomization to death from any cause.


Secondary Outcome Measures:
  • Percentage of Participants With an Objective Response [ Time Frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years) ] [ Designated as safety issue: No ]
    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.

  • Duration of the Objective Response [ Time Frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years) ] [ Designated as safety issue: No ]
    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.

  • 6-month and 1-year Survival [ Time Frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years) ] [ Designated as safety issue: No ]
    6-month and 1-year survival were defined as the percentage of participants who were alive at 6 months and 1 year, respectively.

  • Time to Pain Symptom Progression [ Time Frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.


Enrollment: 602
Study Start Date: February 2011
Estimated Study Completion Date: June 2015
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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 (eg, tamoxifen or aromatase inhibitor) or dual-agent (eg, 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 cross over to receive trastuzumab emtansine 3.6 mg/kg. Patients who crossed over 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.


  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients ≥ 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01419197

  Hide Study Locations
Locations
United States, Arizona
Tucson, Arizona, United States, 85704
United States, Arkansas
Hot Springs, Arkansas, United States, 71913
United States, 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
United States, Colorado
Denver, Colorado, United States, 80220
United States, Connecticut
Trumbull, Connecticut, United States, 06611
United States, Delaware
Newark, Delaware, United States, 19713
United States, District of Columbia
Washington, District of Columbia, United States, 20010
United States, 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
United States, Georgia
Marietta, Georgia, United States, 30060
United States, Idaho
Post Falls, Idaho, United States, 83854
United States, Illinois
Chicago, Illinois, United States, 60612
Chicago, Illinois, United States, 60637
Maywood, Illinois, United States, 60153
United States, Indiana
Fort Wayne, Indiana, United States, 46815
United States, Iowa
Sioux City, Iowa, United States, 51101
United States, Kansas
Wichita, Kansas, United States, 67214-3728
United States, Maine
Scarborough, Maine, United States, 04074
United States, Maryland
Bethesda, Maryland, United States, 20817
Columbia, Maryland, United States, 21044
United States, Massachusetts
Boston, Massachusetts, United States, 02115
Boston, Massachusetts, United States, 02215
Boston, Massachusetts, United States, 02130
United States, Michigan
Detroit, Michigan, United States, 48201
United States, Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Saint Louis, Missouri, United States, 63141
United States, Nebraska
Omaha, Nebraska, United States, 68114
United States, New Jersey
New Brunswick, New Jersey, United States, 08901
United States, New York
Bronx, New York, United States, 10467
Lake Success, New York, United States, 11042
United States, North Carolina
Charlotte, North Carolina, United States, 28203
United States, Ohio
Columbus, Ohio, United States, 43219
United States, Oregon
Portland, Oregon, United States, 97210
United States, Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
Charleston, South Carolina, United States, 29414
United States, Tennessee
Chattanooga, Tennessee, United States, 37404
Nashville, Tennessee, United States, 37232
Nashville, Tennessee, United States, 37203
United States, Texas
Dallas, Texas, United States, 75246
Fort Worth, Texas, United States, 76104
San Antonio, Texas, United States, 78229
United States, Virginia
Richmond, Virginia, United States, 23230
United States, Washington
Seattle, Washington, United States, 98109
Australia, New South Wales
Kogarah, New South Wales, Australia, 2217
Australia, Queensland
South Brisbane, Queensland, Australia, 4101
Australia, Victoria
Frankston, Victoria, Australia, 3199
Australia, Western Australia
Perth, Western Australia, Australia, 6000
Belgium
Leuven, Belgium, 3000
Wilrijk, Belgium, 2610
Brazil
Salvador, BA, Brazil, 41950-610
Goiania, GO, Brazil, 74140-050
Rio de Janeiro, RJ, Brazil, 22260-020
Porto Alegre, RS, Brazil, 90430-090
Itajai, SC, Brazil, 88301-220
Sao Paulo, SP, Brazil, 01509-900
Canada, New Brunswick
Moncton, New Brunswick, Canada, E1C 6Z8
Canada, Ontario
Toronto, Ontario, Canada, M4N 3M5
Canada, Saskatchewan
Regina, Saskatchewan, Canada, S4T 7T1
Saskatoon, Saskatchewan, Canada, S7N 4H4
Canada
Quebec, Canada, G1S 4L8
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, 411 001
Pune, India, 411004
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
Potenza, Basilicata, Italy, 85100
Napoli, Campania, Italy, 80131
Genova, Liguria, Italy, 16132
Bergamo, Lombardia, Italy, 24127
Brescia, Lombardia, Italy, 25123
Milano, Lombardia, Italy, 20132
Milano, Lombardia, Italy, 20121
Biella, Piemonte, Italy, 13900
Cona (Ferrara), Veneto, Italy, 44124
Korea, Republic of
Kyunggi-do, Korea, Republic of, 410-769
Seoul, Korea, Republic of, 120-752
Seoul, Korea, Republic of, 110-744
Seoul, Korea, Republic of, 138-736
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
La Coruna, La Coruña, Spain, 15009
Bilbao, Vizcaya, Spain, 48013
Barcelona, Spain, 08036
Barcelona, Spain, 08907
Madrid, Spain, 28033
Madrid, Spain, 28040
Madrid, Spain, 28034
Malaga, Spain, 29010
Murcia, Spain, 30008
Sevilla, Spain, 41014
Valencia, Spain, 46026
Sweden
Umea, Sweden, 90185
Uppsala, Sweden, 75185
Örebro, Sweden, 701 85
Switzerland
Bern, Switzerland, 3010
Zürich, Switzerland, 8091
Thailand
Bangkok, Thailand, 10400
Bangkok, Thailand, 10110
Bangkok, Thailand, 10700
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
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Abraham C.F. Leung, MD Genentech
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01419197     History of Changes
Other Study ID Numbers: TDM4997g, BO25734, 2011-000509-29
Study First Received: August 16, 2011
Results First Received: February 7, 2014
Last Updated: April 3, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
Ado-trastuzumab emtansine
Maytansine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on August 19, 2014