Clinical trial NCT03084939: Efficacy and Safety of Trastuzumab Emtansine in Chinese Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Locally Advanced or Metastatic Breast Cancer
Official title: A Randomized, Multicenter, Phase III Open-Label Study of the Efficacy and Safety of Trastuzumab Emtansine Versus Lapatinib Plus Capecitabine in Chinese Patients With HER2-Positive Locally Advanced or Metastatic Breast Cancer Who Have Received Prior Trastuzumab-Based Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2017-03-21
Enrollment: 351
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Up to approximately 17 months
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 29 months
measure: Duration of Response (DOR)
timeFrame: Up to approximately 29 months
measure: Overall Survival (OS)
timeFrame: When at least 100 (50%) death events are observed from participants in Stage 1
measure: Number of Participants with Adverse Events
timeFrame: Up to approximately 56 months
measure: Serum Concentration of Trastuzumab Emtansine Conjugate
timeFrame: 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)
measure: Plasma Concentration of N2'-deacetyl-N2'-(3-mercapto-1-oxopropyl)-maytansine (DM1)
timeFrame: Pre-dose on Day 1 of Cycle 1, 15-30 minutes after dose on Day 1 of each 21-day cycle during Cycles 1-4
measure: Serum Concentration of Total Trastuzumab
timeFrame: Pre-dose and 15-30 minutes after dose on Day 1 of each 21-day cycle during Cycles 1-4
measure: Percentage of Participants with Anti-therapeutic Antibodies (ATA) to Trastuzumab Emtansine
timeFrame: Pre-dose on Day 1 of Cycle 1 and Day 1 of Cycle 4, at completion/early termination visit and 3 months after last dose of trastuzumab emtansine (up to approximately 56 months)
measure: Patient-reported Outcome: Percentage of Participants with Clinically Significant Deterioration
timeFrame: Day 1 (prior to any study procedures or discussion of test results) of Cycle 1 (21 days) and every two cycles thereafter until treatment discontinuation and at the completion/early termination visit (up to approximately 56 months)
measure: Patient-reported Outcome: Time to Clinically Significant Deterioration
timeFrame: Day 1 (prior to any study procedures or discussion of test results) of Cycle 1 (21 days) and every two cycles thereafter until treatment discontinuation (up to approximately 56 months)
Other outcomes:
Locations:
city: Beijing City
country: China
facility: Beijing Hospital
city: Beijing
country: China
facility: The Affiliated Hospital of Military Medical Sciences(The 307th Hospital of Chinese PLA)
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Changchun
country: China
facility: the First Hospital of Jilin University
city: Changchun
country: China
facility: Jilin Cancer Hospital
city: Changzhou
country: China
facility: Changzhou First People's Hospital
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: Fuzhou City
country: China
facility: Fujian Medical University Union Hospital
city: Hangzhou City
country: China
facility: Zhejiang Cancer Hospital; Zhejiang Cancer Hospital cancer department
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University College
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Nanjing City
country: China
facility: Jiangsu Cancer Hospital
city: Nanjing
country: China
facility: Jiangsu Province Hospital
city: Shanghai City
country: China
facility: Fudan University Shanghai Cancer Center
city: Shanghai
country: China
facility: Shanghai Jiao Tong University School of Medicine (SJTUSM) - Ruijin Hospital (GuangCi Hospital)
city: Shenyang
country: China
facility: Liaoning cancer Hospital & Institute
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
city: Xi'an
country: China
facility: First Affiliated Hospital of Medical College of Xi'an Jiaotong University
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: