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.
Brief 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
Categories
Completion Date
Completion Date Type
Actual
Conditions
Breast Cancer
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.
* 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.
Inclusion 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.
* 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.
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01419197
Org Class
Industry
Org Full Name
Hoffmann-La Roche
Org Study Id
TDM4997g
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome 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.
Outcome Measure
Progression-free Survival
Outcome Time Frame
Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Outcome Description
Overall survival (OS) was defined as the time from randomization to death from any cause. Overall survival was a co-primary endpoint.
Outcome Measure
Overall Survival
Outcome Time Frame
Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Secondary Ids
Secondary Id
BO25734
Secondary Id
2011-000509-29
Secondary Outcomes
Outcome 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.
Outcome Time Frame
Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Outcome Measure
Percentage of Participants With an Objective Response
Outcome 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.
Outcome Time Frame
Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Outcome Measure
Duration of the Objective Response
Outcome 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.
Outcome Time Frame
Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Outcome Measure
6-month and 1-year Survival
Outcome 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.
Outcome Time Frame
Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Outcome Measure
Time to Pain Symptom Progression
Outcome 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.
Outcome Time Frame
Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Outcome Measure
Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle
Outcome Description
Overall survival was defined as the time from randomization to death from any cause.
Outcome Time Frame
Baseline to the clinical cut-off date of 13 Feb 2015 (up to 4 years)
Outcome Measure
Overall Survival (Final Analysis)
Outcome 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.
Outcome Time Frame
Baseline to the clinical cut-off date of 13 Feb 2015 (up to 4 years)
Outcome Measure
6-month and 1-year Survival (Final Analysis)
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Christine Pellegrino
Investigator Email
CPELLEGR@montefiore.org
Investigator Phone