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NCT01419197 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2016-10-12

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Progression-free Survival

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outcome · POSTED

Overall Survival

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outcome · POSTED

Percentage of Participants With an Objective Response

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outcome · POSTED

Duration of the Objective Response

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outcome · POSTED

6-month and 1-year Survival

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outcome · POSTED

Time to Pain Symptom Progression

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outcome · POSTED

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

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outcome · POSTED

Overall Survival (Final Analysis)

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outcome · POSTED

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

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
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.
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
    intervention Names
    1. Drug: Trastuzumab emtansine
    label
    Trastuzumab emtansine
    type
    EXPERIMENTAL
  2. description
    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.
    intervention Names
    1. Drug: Treatment of physician's choice
    label
    Treatment of physician's choice
    type
    ACTIVE_COMPARATOR
interventions
  1. arm Group Labels
    1. Trastuzumab emtansine
    description
    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.
    name
    Trastuzumab emtansine
    other Names
    1. Kadcyla
    2. T-DM1
    type
    DRUG
  2. arm Group Labels
    1. Treatment of physician's choice
    description
    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.
    name
    Treatment of physician's choice
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
602
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    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.
    measure
    Progression-free Survival
    time Frame
    Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
  2. description
    Overall survival (OS) was defined as the time from randomization to death from any cause. Overall survival was a co-primary endpoint.
    measure
    Overall Survival
    time Frame
    Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
secondary Outcomes
  1. description
    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.
    measure
    Percentage of Participants With an Objective Response
    time Frame
    Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
  2. description
    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.
    measure
    Duration of the Objective Response
    time Frame
    Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
  3. description
    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.
    measure
    6-month and 1-year Survival
    time Frame
    Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
  4. description
    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.
    measure
    Time to Pain Symptom Progression
    time Frame
    Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
  5. description
    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.
    measure
    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)
  6. description
    Overall survival was defined as the time from randomization to death from any cause.
    measure
    Overall Survival (Final Analysis)
    time Frame
    Baseline to the clinical cut-off date of 13 Feb 2015 (up to 4 years)
  7. description
    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.
    measure
    6-month and 1-year Survival (Final Analysis)
    time Frame
    Baseline to the clinical cut-off date of 13 Feb 2015 (up to 4 years)
Full study description
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.
Source references
references
  1. 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.
    pmid
    28733983
    type
    DERIVED
  2. 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.
    pmid
    28526538
    type
    DERIVED
  3. 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.
    pmid
    24793816
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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        reast cancer who had received previous trastuzumab and lapatinib was shown in the randomized phase III <a href="/clinicaltrials/NCT01419197">TH3RESA</a> study (NCT01419197) of T-DM1 versus physician&#8217;s choice of treatment.[<a href="#cit/section_10.76">76</a>][<a href="/Common/PopUps/popDefinition.aspx?id=810017&amp;version=H
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      1. context
        Updated: April 25, 2025
        datetime
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        display
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    Preserved source evidence · Not medical advice