Efficacy and Safety of Trastuzumab Emtansine in Chinese Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Locally Advanced or Metastatic Breast Cancer

Roche

Status and phase: Completed; Phase 3

Conditions: Breast Cancer

Treatments: Drug: Lapatinib; Drug: Capecitabine; Biological: Trastuzumab Emtansine

Study type: Interventional

Funder types: Industry

Identifiers

NCT03084939

BO29919

Details and patient eligibility

About

This is a Phase III, randomized, multicenter, two-arm, open-label study designed to evaluate the safety and efficacy of trastuzumab emtansine compared with that of lapatinib + capecitabine in Chinese participants with HER2-positive, unresectable locally advanced breast cancer (LABC) or metastatic breast cancer (MBC) who have received prior trastuzumab-based therapy. A total of approximately 350 participants will be enrolled in China. The study will consist of 2 stages. Stage 1: Eligible participants will be randomized in a 3:1 ratio to receive either trastuzumab emtansine or control (lapatinib + capecitabine). Stage 2: After Stage 1 is recruited, eligible patients will be enrolled to receive trastuzumab emtansine only.

Enrollment: 351 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Aged >/= 18 years
• Prospective centrally assessed HER2-positive disease (i.e., immunohistochemistry [IHC] 3+ and/or gene amplified [HER2 to Chromosome 17 [CEP 17] ratio >/= 2]) by in situ hybridization (ISH) through use of archival paraffin-embedded tumor tissue
• Histologically or cytologically confirmed invasive breast cancer (BC): incurable, unresectable LABC previously treated with multimodality therapy or MBC
• Prior treatment for BC in the adjuvant, unresectable locally advanced or metastatic setting must include both: a taxane, alone or in combination with another agent, and trastuzumab, alone or in combination with another agent in the adjuvant, unresectable locally advanced or metastatic setting
• Documented progression of incurable, unresectable LABC or MBC, defined by the investigator: progression must occur during or after most recent treatment for LABC or MBC or within 6 months after completing adjuvant therapy
• Measurable and/or non-measurable disease, according the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 definition: CNS-only disease excluded
• Left ventricular ejection fraction (LVEF) >/=50% by either echocardiogram or multiple-gated acquisition
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Adequate organ function evidenced by laboratory results within 30 days prior to randomization
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use non-hormonal contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 7 months after the last dose of study drug
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures (use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year) and agreement to refrain from donating sperm during the treatment period and for at least 7 months after the last dose of study drug

Exclusion criteria

• History of treatment with trastuzumab emtansine
• Prior treatment with lapatinib or capecitabine
• Peripheral neuropathy of Grade >/= 3 per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI CTCAE v4.0)
• History of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage 1 uterine cancer, synchronous or previously diagnosed HER2-positive BC, or cancers with a similar curative outcome as those mentioned above
• History of receiving any anti-cancer drug/biologic or investigational treatment within 21 days prior to randomization, except hormone therapy which can be given up to 7 days prior to randomization
• History of radiation therapy within 14 days before randomization
• Brain metastases that are untreated, symptomatic, progressive, or require therapy such as radiation, surgery or corticosteroid therapy to control symptoms from brain metastases within 30 days before randomization
• History of exposure to cumulative doses of anthracyclines: Doxorubicin > 500 milligrams per square meter (mg/m^2), Epirubucin > 720 mg/m^2, Mitoxantrone > 120 mg/m^2
• Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease)
• Pregnancy or lactation
• Currently known active infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV)
• Presence of conditions that could affect gastrointestinal absorption
• History of intolerance (including Grade 3 or 4 infusion reaction) or hypersensitivity to trastuzumab or murine proteins
• Known hypersensitivity to 5-fluorouracil or known dihydropyrimidine dehydrogenase deficiency
• Current treatment with sorivudine or its chemically related analogs

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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351 participants in 2 patient groups

Trastuzumab Emtansine

Experimental group

Description:

Participants with HER2-positive, unresectable LABC or MBC who have experienced disease progression after treatment with trastuzumab and a taxane will be treated with trastuzumab emtansine. Participants may continue to receive study treatment until disease progression (as assessed by the investigator), unmanageable toxicity, or study termination by the Sponsor.

Treatment:

Biological: Trastuzumab Emtansine

Control (lapatinib + capecitabine)

Active Comparator group

Description:

Participants with HER2-positive, unresectable LABC or MBC who have experienced disease progression after treatment with trastuzumab and a taxane will be treated with lapatinib plus capecitabine. Participants may continue to receive study treatment until disease progression (as assessed by the investigator), unmanageable toxicity, or study termination by the Sponsor.

Treatment:

Drug: Lapatinib

Drug: Capecitabine