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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
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Arizona
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Murcia
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Sevilla
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Valencia
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Umea
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Westcliffe-on-sea
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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