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 (TH3RESA)

Roche

Status and phase: Completed; Phase 3

Conditions: Breast Cancer

Treatments: Drug: Treatment of physician's choice; Drug: Trastuzumab emtansine

Study type: Interventional

Funder types: Industry

Identifiers

NCT01419197

BO25734 (Other Identifier)

TDM4997g

2011-000509-29 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 602 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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602 participants in 2 patient groups

Trastuzumab emtansine

Experimental group

Description:

Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.

Treatment:

Drug: Trastuzumab emtansine

Treatment of physician's choice

Active Comparator group

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.

Treatment:

Drug: Treatment of physician's choice