Overview

This trial is active, not recruiting.

Condition breast cancer
Treatments trastuzumab emtansine, treatment of physician's choice
Phase phase 3
Sponsor Hoffmann-La Roche
Start date February 2011
End date February 2013
Trial size 602 participants
Trial identifier NCT01419197, 2011-000509-29, BO25734, TDM4997g

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 patients with metastatic or unresectable locally advanced/recurrent HER2-positive breast cancer. Eligible patients will be randomized to receive either trastuzumab emtansine 3.6 mg/kg intravenously every 21 days or treatment of the physician's choice. Patients continue to receive study treatment until disease progression or unacceptable toxicity occurs. This study is also known under Roche study protocol number BO25734.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
trastuzumab emtansine Kadcyla
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.
(Active Comparator)
Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity.
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 (eg, tamoxifen or aromatase inhibitor) or dual-agent (eg, 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 cross over to receive trastuzumab emtansine 3.6 mg/kg. Patients who crossed over 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.

Primary Outcomes

Measure
Progression-free Survival
time frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Overall Survival
time frame: 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
time frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Duration of the Objective Response
time frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
6-month and 1-year Survival
time frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Time to Pain Symptom Progression
time frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
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)

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Adult patients ≥ 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.

Additional Information

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
Trial information was received from ClinicalTrials.gov and was last updated in April 2014.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.