Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01419197




Registration number
NCT01419197
Ethics application status
Date submitted
16/08/2011
Date registered
18/08/2011
Date last updated
12/10/2016

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
BO25734
Secondary ID [2] 0 0
TDM4997g
Universal Trial Number (UTN)
Trial acronym
TH3RESA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Trastuzumab emtansine
Treatment: Drugs - Treatment of physician's choice

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

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.


Treatment: Drugs: 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.

Treatment: Drugs: 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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival
Timepoint [1] 0 0
Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Primary outcome [2] 0 0
Overall Survival
Timepoint [2] 0 0
Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Secondary outcome [1] 0 0
Percentage of Participants With an Objective Response
Timepoint [1] 0 0
Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Secondary outcome [2] 0 0
Duration of the Objective Response
Timepoint [2] 0 0
Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Secondary outcome [3] 0 0
6-month and 1-year Survival
Timepoint [3] 0 0
Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Secondary outcome [4] 0 0
Time to Pain Symptom Progression
Timepoint [4] 0 0
Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Secondary outcome [5] 0 0
Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle
Timepoint [5] 0 0
Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Secondary outcome [6] 0 0
Overall Survival (Final Analysis)
Timepoint [6] 0 0
Baseline to the clinical cut-off date of 13 Feb 2015 (up to 4 years)
Secondary outcome [7] 0 0
6-month and 1-year Survival (Final Analysis)
Timepoint [7] 0 0
Baseline to the clinical cut-off date of 13 Feb 2015 (up to 4 years)

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/08/2015
Sample size
Target
Accrual to date
Final
602
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
- Kogarah
Recruitment hospital [2] 0 0
- South Brisbane
Recruitment hospital [3] 0 0
- Frankston
Recruitment hospital [4] 0 0
- Perth
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
3199 - Frankston
Recruitment postcode(s) [4] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Delaware
Country [7] 0 0
United States of America
State/province [7] 0 0
District of Columbia
Country [8] 0 0
United States of America
State/province [8] 0 0
Florida
Country [9] 0 0
United States of America
State/province [9] 0 0
Georgia
Country [10] 0 0
United States of America
State/province [10] 0 0
Idaho
Country [11] 0 0
United States of America
State/province [11] 0 0
Illinois
Country [12] 0 0
United States of America
State/province [12] 0 0
Indiana
Country [13] 0 0
United States of America
State/province [13] 0 0
Iowa
Country [14] 0 0
United States of America
State/province [14] 0 0
Kansas
Country [15] 0 0
United States of America
State/province [15] 0 0
Maine
Country [16] 0 0
United States of America
State/province [16] 0 0
Maryland
Country [17] 0 0
United States of America
State/province [17] 0 0
Massachusetts
Country [18] 0 0
United States of America
State/province [18] 0 0
Michigan
Country [19] 0 0
United States of America
State/province [19] 0 0
Minnesota
Country [20] 0 0
United States of America
State/province [20] 0 0
Missouri
Country [21] 0 0
United States of America
State/province [21] 0 0
Nebraska
Country [22] 0 0
United States of America
State/province [22] 0 0
New Jersey
Country [23] 0 0
United States of America
State/province [23] 0 0
New York
Country [24] 0 0
United States of America
State/province [24] 0 0
North Carolina
Country [25] 0 0
United States of America
State/province [25] 0 0
Ohio
Country [26] 0 0
United States of America
State/province [26] 0 0
Oregon
Country [27] 0 0
United States of America
State/province [27] 0 0
Pennsylvania
Country [28] 0 0
United States of America
State/province [28] 0 0
South Carolina
Country [29] 0 0
United States of America
State/province [29] 0 0
Tennessee
Country [30] 0 0
United States of America
State/province [30] 0 0
Texas
Country [31] 0 0
United States of America
State/province [31] 0 0
Virginia
Country [32] 0 0
United States of America
State/province [32] 0 0
Washington
Country [33] 0 0
Belgium
State/province [33] 0 0
Leuven
Country [34] 0 0
Belgium
State/province [34] 0 0
Wilrijk
Country [35] 0 0
Brazil
State/province [35] 0 0
BA
Country [36] 0 0
Brazil
State/province [36] 0 0
GO
Country [37] 0 0
Brazil
State/province [37] 0 0
RJ
Country [38] 0 0
Brazil
State/province [38] 0 0
RS
Country [39] 0 0
Brazil
State/province [39] 0 0
SC
Country [40] 0 0
Brazil
State/province [40] 0 0
SP
Country [41] 0 0
Canada
State/province [41] 0 0
New Brunswick
Country [42] 0 0
Canada
State/province [42] 0 0
Ontario
Country [43] 0 0
Canada
State/province [43] 0 0
Saskatchewan
Country [44] 0 0
Canada
State/province [44] 0 0
Quebec
Country [45] 0 0
Czech Republic
State/province [45] 0 0
Brno
Country [46] 0 0
Czech Republic
State/province [46] 0 0
Hradec Kralove
Country [47] 0 0
Czech Republic
State/province [47] 0 0
Olomouc
Country [48] 0 0
Czech Republic
State/province [48] 0 0
Praha 2
Country [49] 0 0
Czech Republic
State/province [49] 0 0
Praha 5
Country [50] 0 0
France
State/province [50] 0 0
Angers
Country [51] 0 0
France
State/province [51] 0 0
Bordeaux
Country [52] 0 0
France
State/province [52] 0 0
Caen
Country [53] 0 0
France
State/province [53] 0 0
Lyon
Country [54] 0 0
France
State/province [54] 0 0
Montpellier cedex 5
Country [55] 0 0
France
State/province [55] 0 0
Nantes
Country [56] 0 0
France
State/province [56] 0 0
Nice
Country [57] 0 0
France
State/province [57] 0 0
Nimes
Country [58] 0 0
France
State/province [58] 0 0
Paris
Country [59] 0 0
France
State/province [59] 0 0
Reims CEDEX
Country [60] 0 0
France
State/province [60] 0 0
Rouen
Country [61] 0 0
France
State/province [61] 0 0
St-Priest-En-Jarez
Country [62] 0 0
France
State/province [62] 0 0
Strasbourg
Country [63] 0 0
France
State/province [63] 0 0
Toulouse
Country [64] 0 0
France
State/province [64] 0 0
Tours
Country [65] 0 0
France
State/province [65] 0 0
Villejuif
Country [66] 0 0
Germany
State/province [66] 0 0
Bielefeld
Country [67] 0 0
Germany
State/province [67] 0 0
Hamburg
Country [68] 0 0
Germany
State/province [68] 0 0
Hannover
Country [69] 0 0
Germany
State/province [69] 0 0
Kiel
Country [70] 0 0
Germany
State/province [70] 0 0
Mainz
Country [71] 0 0
Germany
State/province [71] 0 0
München
Country [72] 0 0
Germany
State/province [72] 0 0
Ravensburg
Country [73] 0 0
Germany
State/province [73] 0 0
Recklinghausen
Country [74] 0 0
Germany
State/province [74] 0 0
Stuttgart
Country [75] 0 0
Germany
State/province [75] 0 0
Trier
Country [76] 0 0
Germany
State/province [76] 0 0
Troisdorf
Country [77] 0 0
Hungary
State/province [77] 0 0
Budapest
Country [78] 0 0
Hungary
State/province [78] 0 0
Gyula
Country [79] 0 0
Hungary
State/province [79] 0 0
Kecskemet
Country [80] 0 0
Hungary
State/province [80] 0 0
Miskolc
Country [81] 0 0
Hungary
State/province [81] 0 0
Szeged
Country [82] 0 0
Hungary
State/province [82] 0 0
Szolnok
Country [83] 0 0
India
State/province [83] 0 0
Bangalore
Country [84] 0 0
India
State/province [84] 0 0
Chennai
Country [85] 0 0
India
State/province [85] 0 0
Kolkata
Country [86] 0 0
India
State/province [86] 0 0
New Delhi
Country [87] 0 0
India
State/province [87] 0 0
Pune
Country [88] 0 0
Israel
State/province [88] 0 0
Beer Sheva
Country [89] 0 0
Israel
State/province [89] 0 0
Hafia
Country [90] 0 0
Israel
State/province [90] 0 0
Jerusalem
Country [91] 0 0
Israel
State/province [91] 0 0
Petach Tikva
Country [92] 0 0
Israel
State/province [92] 0 0
Ramat-Gan
Country [93] 0 0
Israel
State/province [93] 0 0
Rehovot
Country [94] 0 0
Israel
State/province [94] 0 0
Tel Aviv
Country [95] 0 0
Italy
State/province [95] 0 0
Basilicata
Country [96] 0 0
Italy
State/province [96] 0 0
Campania
Country [97] 0 0
Italy
State/province [97] 0 0
Liguria
Country [98] 0 0
Italy
State/province [98] 0 0
Lombardia
Country [99] 0 0
Italy
State/province [99] 0 0
Piemonte
Country [100] 0 0
Italy
State/province [100] 0 0
Veneto
Country [101] 0 0
Korea, Republic of
State/province [101] 0 0
Kyunggi-do
Country [102] 0 0
Korea, Republic of
State/province [102] 0 0
Seoul
Country [103] 0 0
Norway
State/province [103] 0 0
Oslo
Country [104] 0 0
Poland
State/province [104] 0 0
Bialystok
Country [105] 0 0
Poland
State/province [105] 0 0
Bydgoszcz
Country [106] 0 0
Poland
State/province [106] 0 0
Gdansk
Country [107] 0 0
Poland
State/province [107] 0 0
Lublin
Country [108] 0 0
Poland
State/province [108] 0 0
Poznan
Country [109] 0 0
Poland
State/province [109] 0 0
Warszawa
Country [110] 0 0
Russian Federation
State/province [110] 0 0
Moscow
Country [111] 0 0
Russian Federation
State/province [111] 0 0
Samara
Country [112] 0 0
Russian Federation
State/province [112] 0 0
Stavropol
Country [113] 0 0
Slovakia
State/province [113] 0 0
Kosice
Country [114] 0 0
Slovakia
State/province [114] 0 0
Poprad
Country [115] 0 0
Spain
State/province [115] 0 0
La Coruña
Country [116] 0 0
Spain
State/province [116] 0 0
Vizcaya
Country [117] 0 0
Spain
State/province [117] 0 0
Barcelona
Country [118] 0 0
Spain
State/province [118] 0 0
Madrid
Country [119] 0 0
Spain
State/province [119] 0 0
Malaga
Country [120] 0 0
Spain
State/province [120] 0 0
Murcia
Country [121] 0 0
Spain
State/province [121] 0 0
Sevilla
Country [122] 0 0
Spain
State/province [122] 0 0
Valencia
Country [123] 0 0
Sweden
State/province [123] 0 0
Umea
Country [124] 0 0
Sweden
State/province [124] 0 0
Uppsala
Country [125] 0 0
Sweden
State/province [125] 0 0
Örebro
Country [126] 0 0
Switzerland
State/province [126] 0 0
Bern
Country [127] 0 0
Switzerland
State/province [127] 0 0
Zürich
Country [128] 0 0
Thailand
State/province [128] 0 0
Bangkok
Country [129] 0 0
United Kingdom
State/province [129] 0 0
Brighton
Country [130] 0 0
United Kingdom
State/province [130] 0 0
Guildford
Country [131] 0 0
United Kingdom
State/province [131] 0 0
London
Country [132] 0 0
United Kingdom
State/province [132] 0 0
Maidstone
Country [133] 0 0
United Kingdom
State/province [133] 0 0
Nottingham
Country [134] 0 0
United Kingdom
State/province [134] 0 0
Sheffield
Country [135] 0 0
United Kingdom
State/province [135] 0 0
Stoke-on-Trent
Country [136] 0 0
United Kingdom
State/province [136] 0 0
Westcliffe-on-sea
Country [137] 0 0
United Kingdom
State/province [137] 0 0
Wirral

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT01419197