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

NCT03084939 | Completed Phase 3

• 1 other identifier: BO29919
• Study Type: interventional
• Target: 351
• Locations: 1 country
• Sites: 18

Brief Summary

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  PFS is defined as the time from randomization to the first occurrence of disease progression as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) Version (v1.1), or death from any cause during the study, whichever occurs first. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 millimeter (mm) taking as reference the smallest sum during the study including baseline or the appearance of one or more new lesions. Tumor assessments will be performed with computed tomography (CT) or magnetic resonance imaging (MRI) scans.

  Up to approximately 17 months

Secondary Outcomes (10)

• Objective Response Rate (ORR)

  Up to approximately 29 months

• Duration of Response (DOR)

  Up to approximately 29 months

• Overall Survival (OS)

  When at least 100 (50%) death events are observed from participants in Stage 1

• Number of Participants with Adverse Events

  Up to approximately 56 months

• Serum Concentration of Trastuzumab Emtansine Conjugate

  Pre-dose and 15-30 minutes after dose on Day 1 of each 21-day cycle during Cycles 1-4 and at completion/early termination visit (up to approximately 56 months)

Study Arms (2)

Trastuzumab Emtansine

EXPERIMENTAL

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.

Biological: Trastuzumab Emtansine

Control (lapatinib + capecitabine)

ACTIVE COMPARATOR

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.

Drug: Lapatinib; Drug: Capecitabine

Interventions

Trastuzumab Emtansine BIOLOGICAL

Trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) was administered intravenously on Day 1 of each 21-day cycle.

Also known as: Kadcyla

Trastuzumab Emtansine

Lapatinib DRUG

Lapatinib 1250 mg was administered orally once per day of each 21-day cycle.

Control (lapatinib + capecitabine)

Capecitabine DRUG

Capecitabine 1000 milligrams per square meter (mg/m\^2) was administered orally twice daily on Days 1-14 of each 21-day cycle.

Control (lapatinib + capecitabine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (18)

Beijing Hospital

Beijing, 100006, China

Location

The Affiliated Hospital of Military Medical Sciences(The 307th Hospital of Chinese PLA)

Beijing, 100071, China

Location

Beijing Cancer Hospital

Beijing, 100142, China

Location

the First Hospital of Jilin University

Changchun, 130021, China

Location

Jilin Cancer Hospital

Changchun, 132013, China

Location

Changzhou First People's Hospital

Changzhou, 213003, China

Location

West China Hospital, Sichuan University

Chengdu, 610041, China

Location

Fujian Medical University Union Hospital

Fuzhou, 350001, China

Location

The Second Affiliated Hospital of Zhejiang University College

Hangzhou, 310009, China

Location

Zhejiang Cancer Hospital; Zhejiang Cancer Hospital cancer department

Hangzhou, 310022, China

Location

Harbin Medical University Cancer Hospital

Harbin, 150081, China

Location

Jiangsu Province Hospital

Nanjing, 210008, China

Location

Jiangsu Cancer Hospital

Nanjing, 211100, China

Location

Shanghai Jiao Tong University School of Medicine (SJTUSM) - Ruijin Hospital (GuangCi Hospital)

Shanghai, 200025, China

Location

Fudan University Shanghai Cancer Center

Shanghai, 200120, China

Location

Liaoning cancer Hospital & Institute

Shenyang, 110042, China

Location

Tianjin Cancer Hospital

Tianjin, 300060, China

Location

First Affiliated Hospital of Medical College of Xi'an Jiaotong University

Xi'an, 710061, China

Location

Related Publications (1)

• Wang X, Li W, Yin Y, Tong Z, Zhang Q, Zheng H, Shao Z, Li H, Yang J, Feng J, Wu F, Lamour F, Restuccia E, Jiang Z. Primary results of ELAINA: a randomized, multicenter, open-label, phase III study of the efficacy and safety of trastuzumab emtansine vs. lapatinib plus capecitabine in Chinese patients with HER2-positive locally advanced or metastatic breast cancer who have received prior trastuzumab-based therapy. Transl Breast Cancer Res. 2023 Jan 31;4:3. doi: 10.21037/tbcr-23-2. eCollection 2023.

  PMID: 38751488 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Ado-Trastuzumab Emtansine; Lapatinib; Capecitabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Trastuzumab; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2017
• First Posted: March 21, 2017
• Study Start: April 24, 2017
• Primary Completion: November 23, 2018
• Study Completion: March 14, 2023
• Last Updated: May 6, 2023

Record last verified: 2023-05

Locations

CN (18)