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

Phase 3

Completed

• Conditions: Breast Cancer
• Interventions: Drug: Trastuzumab emtansine; Drug: Treatment of physician's choice

• Registration Number: NCT01419197
• Lead Sponsor: Hoffmann-La Roche

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.

Detailed Description

Not available

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Related News

Study Timeline

• Study First Submitted: 2011-08-16
• Study First Submitted QC: 2011-08-16
• Study First Posted: 2011-08-18
• Study Start: 2011-09
• Primary Completion: 2013-02
• Results First Submitted: 2014-02-07
• Results First Submitted QC: 2014-04-03
• Results First Posted: 2014-05-05
• Study Completion: 2015-08
• Status Verified: 2016-08
• Last Update Submitted: 2016-08-17
• Last Update Posted: 2016-10-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 602

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.

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Trastuzumab emtansine	Trastuzumab emtansine	Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
Treatment of physician's choice	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.

Primary Outcome Measures

Name	Time	Method
Progression-free Survival	Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)	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.
Overall Survival	Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)	Overall survival (OS) was defined as the time from randomization to death from any cause. Overall survival was a co-primary endpoint.

Secondary Outcome Measures

Name	Time	Method
Time to Pain Symptom Progression	Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)	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.
Percentage of Participants With an Objective Response	Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)	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.
Duration of the Objective Response	Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)	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.
6-month and 1-year Survival	Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)	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.
Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle	Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)	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.
Overall Survival (Final Analysis)	Baseline to the clinical cut-off date of 13 Feb 2015 (up to 4 years)	Overall survival was defined as the time from randomization to death from any cause.
6-month and 1-year Survival (Final Analysis)	Baseline to the clinical cut-off date of 13 Feb 2015 (up to 4 years)	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.