A Study of Trastuzumab Emtansine in Comparison With Treatment of Physician's Choice in Patients With HER2-positive Breast Cancer Who Have Received at Least Two Prior Regimens of HER2-directed Therapy

Breast Cancer Clinical Trial

— TH3RESA  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01419197
• Other study ID #: TDM4997g
• Secondary ID: BO257342011-0005
• Status: Active, not recruiting
• Phase: Phase 3
• First received: August 16, 2011
• Last updated: April 3, 2014
• Start date: February 2011
• Est. completion date: June 2015

Study information

• Verified date: April 2014
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 602
• Est. completion date: June 2015
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• 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 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Canada,  Czech Republic,  France,  Germany,  Hungary,  India,  Israel,  Italy,  Korea, Republic of,  Norway,  Poland,  Russian Federation,  Slovakia,  Spain,  Sweden,  Switzerland,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival	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.	Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)	No
Primary	Overall Survival	Overall survival was defined as the time from randomization to death from any cause.	Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)	No
Secondary	Percentage of Participants With an Objective Response	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.	Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)	No
Secondary	Duration of the Objective Response	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.	Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)	No
Secondary	6-month and 1-year Survival	6-month and 1-year survival were defined as the percentage of participants who were alive at 6 months and 1 year, respectively.	Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)	No
Secondary	Time to Pain Symptom Progression	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.	Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)	No
Secondary	Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle	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.	Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)	No