Clinical trial NCT01419197: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2011-08-18
Enrollment: 602
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Progression-free Survival
timeFrame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
measure: Overall Survival
timeFrame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Secondary outcomes:
measure: Percentage of Participants With an Objective Response
timeFrame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
measure: Duration of the Objective Response
timeFrame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
measure: 6-month and 1-year Survival
timeFrame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
measure: Time to Pain Symptom Progression
timeFrame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
measure: Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle
timeFrame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
measure: Overall Survival (Final Analysis)
timeFrame: Baseline to the clinical cut-off date of 13 Feb 2015 (up to 4 years)
measure: 6-month and 1-year Survival (Final Analysis)
timeFrame: Baseline to the clinical cut-off date of 13 Feb 2015 (up to 4 years)
Other outcomes:
Locations:
city: Tucson
country: United States
state: Arizona
city: Hot Springs
country: United States
state: Arkansas
city: Hayward
country: United States
state: California
city: Highland
country: United States
state: California
city: Oakland
country: United States
state: California
city: Roseville
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Francisco
country: United States
state: California
city: San Jose
country: United States
state: California
city: Santa Clara
country: United States
state: California
city: South San Francisco
country: United States
state: California
city: Stockton
country: United States
state: California
city: Vallejo
country: United States
state: California
city: Walnut Creek
country: United States
state: California
city: West Hollywood
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Trumbull
country: United States
state: Connecticut
city: Newark
country: United States
state: Delaware
city: Washington
country: United States
state: District of Columbia
city: Coral Springs
country: United States
state: Florida
city: Deerfield Beach
country: United States
state: Florida
city: Fort Myers
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state: Florida
city: Jacksonville
country: United States
state: Florida
city: Plantation
country: United States
state: Florida
city: Marietta
country: United States
state: Georgia
city: Post Falls
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state: Idaho
city: Chicago
country: United States
state: Illinois
city: Chicago
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state: Illinois
city: Maywood
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state: Illinois
city: Fort Wayne
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state: Indiana
city: Sioux City
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state: Iowa
city: Wichita
country: United States
state: Kansas
city: Scarborough
country: United States
state: Maine
city: Bethesda
country: United States
state: Maryland
city: Columbia
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state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Boston
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state: Massachusetts
city: Boston
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city: Detroit
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state: Michigan
city: Minneapolis
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state: Missouri
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state: Nebraska
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state: New Jersey
city: Bronx
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state: New York
city: Lake Success
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state: North Carolina
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city: Chattanooga
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state: Tennessee
city: Nashville
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state: Tennessee
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state: Tennessee
city: Dallas
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state: Texas
city: Fort Worth
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state: Texas
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city: Richmond
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state: Virginia
city: Seattle
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state: Washington
city: Kogarah
country: Australia
state: New South Wales
city: South Brisbane
country: Australia
state: Queensland
city: Frankston
country: Australia
state: Victoria
city: Perth
country: Australia
state: Western Australia
city: Leuven
country: Belgium
city: Wilrijk
country: Belgium
city: Salvador
country: Brazil
state: BA
city: Goiania
country: Brazil
state: GO
city: Rio de Janeiro
country: Brazil
state: RJ
city: Porto Alegre
country: Brazil
state: RS
city: Itajai
country: Brazil
state: SC
city: Sao Paulo
country: Brazil
state: SP
city: Moncton
country: Canada
state: New Brunswick
city: Toronto
country: Canada
state: Ontario
city: Regina
country: Canada
state: Saskatchewan
city: Saskatoon
country: Canada
state: Saskatchewan
city: Quebec
country: Canada
city: Brno
country: Czech Republic
city: Hradec Kralove
country: Czech Republic
city: Olomouc
country: Czech Republic
city: Praha 2
country: Czech Republic
city: Praha 5
country: Czech Republic
city: Angers
country: France
city: Bordeaux
country: France
city: Caen
country: France
city: Lyon
country: France
city: Montpellier cedex 5
country: France
city: Nantes
country: France
city: Nice
country: France
city: Nimes
country: France
city: Paris
country: France
city: Reims CEDEX
country: France
city: Rouen
country: France
city: St-Priest-En-Jarez
country: France
city: Strasbourg
country: France
city: Toulouse
country: France
city: Toulouse
country: France
city: Tours
country: France
city: Villejuif
country: France
city: Bielefeld
country: Germany
city: Hamburg
country: Germany
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country: Germany
city: Hannover
country: Germany
city: Kiel
country: Germany
city: Mainz
country: Germany
city: München
country: Germany
city: Ravensburg
country: Germany
city: Recklinghausen
country: Germany
city: Stuttgart
country: Germany
city: Trier
country: Germany
city: Troisdorf
country: Germany
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Gyula
country: Hungary
city: Kecskemet
country: Hungary
city: Miskolc
country: Hungary
city: Szeged
country: Hungary
city: Szolnok
country: Hungary
city: Bangalore
country: India
city: Chennai
country: India
city: Kolkata
country: India
city: New Delhi
country: India
city: Pune
country: India
city: Pune
country: India
city: Beer Sheva
country: Israel
city: Hafia
country: Israel
city: Jerusalem
country: Israel
city: Petach Tikva
country: Israel
city: Ramat-Gan
country: Israel
city: Rehovot
country: Israel
city: Tel Aviv
country: Israel
city: Potenza
country: Italy
state: Basilicata
city: Napoli
country: Italy
state: Campania
city: Genova
country: Italy
state: Liguria
city: Bergamo
country: Italy
state: Lombardia
city: Brescia
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Biella
country: Italy
state: Piemonte
city: Cona (Ferrara)
country: Italy
state: Veneto
city: Kyunggi-do
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Oslo
country: Norway
city: Bialystok
country: Poland
city: Bydgoszcz
country: Poland
city: Gdansk
country: Poland
city: Lublin
country: Poland
city: Poznan
country: Poland
city: Warszawa
country: Poland
city: Moscow
country: Russian Federation
city: Samara
country: Russian Federation
city: Stavropol
country: Russian Federation
city: Kosice
country: Slovakia
city: Poprad
country: Slovakia
city: La Coruna
country: Spain
state: La Coruña
city: Bilbao
country: Spain
state: Vizcaya
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Malaga
country: Spain
city: Murcia
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Umea
country: Sweden
city: Uppsala
country: Sweden
city: Örebro
country: Sweden
city: Bern
country: Switzerland
city: Zürich
country: Switzerland
city: Bangkok
country: Thailand
city: Bangkok
country: Thailand
city: Bangkok
country: Thailand
city: Brighton
country: United Kingdom
city: Guildford
country: United Kingdom
city: London
country: United Kingdom
city: Maidstone
country: United Kingdom
city: Nottingham
country: United Kingdom
city: Sheffield
country: United Kingdom
city: Stoke-on-Trent
country: United Kingdom
city: Westcliffe-on-sea
country: United Kingdom
city: Wirral
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.