Phase III, Randomized, Multicenter, Double-blind study to compare efficacy and safety of EG12014 (Eirgenix Trastuzumab) with Herceptin® as Neoadjuvant treatment in combination with Anthracycline/Paclitaxel-based systemic therapy in patients with HER2-positive Early breast cancer
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- Eirgenix Inc
- 入组人数
- 800
- 试验地点
- 9
- 主要终点
- equivalence of EG12014 and Herceptin, both given in combination
研究概览
简要总结
This international, Phase III, randomized, double-blind clinical study is to prove equivalence, regarding safety and efficacy (the EMA position), and to demonstrate that there are no clinically meaningful differences in terms of response, safety, purity, and potency (the FDA position) between EG12014 and EU licensed Herceptin. Thereby, the FDA could accept the EGC002 study findings in exactly the same way for US-licensed Herceptin.
In this study, the proposed biosimilar (EG12014), and EU-licensed Herceptin will be studied in patients with EBC (i.e., with operable disease, stage T3N1M0), who constitute a sensitive and homogeneous population. Patients with locally advanced breast cancer (LABC) with stage T3N2-3M0 or greater will be excluded. pCR will be evaluated in the neoadjuvant setting, in order to provide a robust basis for regulatory approval of EG12014 as a proposed biosimilar product to Herceptin.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant, Investigator and Outcome Assessor Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- Female
入选标准
- •Patients will be entered into this study only if they meet all of the following criteria:
- •Provide signed and dated written informed consent before entering the study.
- •Female, ≥18 and ≤65 years of age.
- •Histologically-confirmed invasive carcinoma of the breast (American Joint Committee on Cancer [AJCC] Stage II, IIIa [43]).
- •Operable breast cancer, planned surgical resection of breast tumor (mastectomy or lumpectomy) and sentinel or axillary lymph nodes.
- •Ipsilateral, measurable tumor of the breast ≥2 cm in diameter.
- •HER2-positive tumor, defined as 3+ score by IHC or fluorescence positive by FISH.
- •Known estrogen receptor (ER) and progesterone receptor (PrR) status at study entry.
- •Adequate bone marrow function, defined as granulocyte count of ≥1.500/μL, and platelet count of ≥100.000/μL.
- •Adequate hepatic and renal function, defined as: bilirubin within normal range alanine aminotransferase (ALT) ≤2 x upper limit of normal (ULN) aspartate aminotransferase (AST) ≤2 x ULN gamma glutamyl transferase (GGT) ≤3 x ULN serum creatinine <1.5 mg/dL
- •International normalized ratio ≤1.5×ULN (2 to 3×ULN if on anticoagulants) or prothrombin time ≤1.5×ULN; activated partial thromboplastin time ≤1.5×ULN.
- •Hemoglobin concentrations within the normal ranges.
- •Eastern Cooperative Oncology Group (ECOG) score of 0 or
- •LVEF ≥55%, measured by multiple-gated acquisition (MUGA) scan or echocardiography.
- •Negative pregnancy test at entry, women of childbearing potential have to use contraceptives during the course of the study.
- •Females with childbearing potential must provide a negative serum pregnancy test at Screening and must be using adequate birth control.
- •Adequate birth control is defined as agreement to consistently practice an effective and accepted method of contraception throughout the duration of the study and for 6 months after study drug treatment.
- •These methods include hormonal contraceptives, intrauterine device, or double barrier contraception (i.e., condom + diaphragm) or a male partner with documented vasectomy.
- •Non-childbearing potential is defined as post-menopausal for at least 1 year or surgical sterilization or hysterectomy at least 3 months before study start.
- •4.2 Inclusion Criterion after Surgery (Adjuvant Part of the Study) After completion of the neoadjuvant part of the study and surgery, patients will be eligible for double-blind adjuvant therapy with EG12014 or Herceptin if they meet the following criterion:
- •No sequelae have occurred after neoadjuvant therapy, in particular regarding cardiac function.
- •No separate informed consent is required.
排除标准
- •Patients will be entered into this study only if they meet none of the following criteria:
- •Bilateral breast cancer.
- •Pregnancy or lactation or considering becoming pregnant.
- •Metastases, other than sentinel/axillary lymph nodes.
- •Previous treatment (chemotherapy, biologic therapy, radiation, or surgery) for invasive malignant disease or other concomitant active malignancy, other than basal-cell carcinoma of the skin.
- •Previous treatment for carcinoma in situ of the cervix is allowed.
- •Other serious illness or medical disorder.
- •Previous treatment with Herceptin.
- •Angina pectoris or arrhythmia requiring medication; poorly controlled hypertension; left ventricular hypertrophy on echocardiography; history of myocardial infarction or cardiac failure, New York Heart Association (NYHA) class II or higher; clinically significant cardiac valvular disease; hemodynamic effective pericardial effusion; other cardiomyopathies; coronary artery disease; LVEF of <55%.
- •Any investigational treatment less than 30 days prior to study entry, or within a time interval less than at least 5 half-lives of the investigational medicinal product, whichever is longer.
- •Positive diagnostic test for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV).
- •History of hypersensitivity to the study drug or to drugs with similar chemical structures.
- •History of, or known current problems with, drug or alcohol abuse.
- •Other serious illness, medical disorder or condition that, in the opinion of the Investigator, would make the patient unsuitable for participation in the study.
结局指标
主要结局
equivalence of EG12014 and Herceptin, both given in combination
时间窗: Tumor response will be evaluated after completion of the neoadjuvant treatment and prior to surgery by clinical examination, mammography, and /or ultrasound and CT/MRI. Resected specimens of breast tissue and axillary lymph nodes will be evaluated for | pathological response by a central laboratory, and used for the assessment of the primary | endpoint.
with paclitaxel for 12 weeks (4 cycles) as part of neoadjuvant
时间窗: Tumor response will be evaluated after completion of the neoadjuvant treatment and prior to surgery by clinical examination, mammography, and /or ultrasound and CT/MRI. Resected specimens of breast tissue and axillary lymph nodes will be evaluated for | pathological response by a central laboratory, and used for the assessment of the primary | endpoint.
therapy in patients with human epidermal growth factor receptor 2
时间窗: Tumor response will be evaluated after completion of the neoadjuvant treatment and prior to surgery by clinical examination, mammography, and /or ultrasound and CT/MRI. Resected specimens of breast tissue and axillary lymph nodes will be evaluated for | pathological response by a central laboratory, and used for the assessment of the primary | endpoint.
(HER2)-positive early breast cancer (EBC), in terms of efficacy
时间窗: Tumor response will be evaluated after completion of the neoadjuvant treatment and prior to surgery by clinical examination, mammography, and /or ultrasound and CT/MRI. Resected specimens of breast tissue and axillary lymph nodes will be evaluated for | pathological response by a central laboratory, and used for the assessment of the primary | endpoint.
The primary objective of this study is to demonstrate therapeutic
时间窗: Tumor response will be evaluated after completion of the neoadjuvant treatment and prior to surgery by clinical examination, mammography, and /or ultrasound and CT/MRI. Resected specimens of breast tissue and axillary lymph nodes will be evaluated for | pathological response by a central laboratory, and used for the assessment of the primary | endpoint.
determined by pathological complete response (pCR) (ypT0/is ypN0)
时间窗: Tumor response will be evaluated after completion of the neoadjuvant treatment and prior to surgery by clinical examination, mammography, and /or ultrasound and CT/MRI. Resected specimens of breast tissue and axillary lymph nodes will be evaluated for | pathological response by a central laboratory, and used for the assessment of the primary | endpoint.
at the time of surgery, assessed by central laboratory.
时间窗: Tumor response will be evaluated after completion of the neoadjuvant treatment and prior to surgery by clinical examination, mammography, and /or ultrasound and CT/MRI. Resected specimens of breast tissue and axillary lymph nodes will be evaluated for | pathological response by a central laboratory, and used for the assessment of the primary | endpoint.
次要结局
- Further evaluation of pCR at surgery (ypT0 ypN0, and ypT0/is)(pCR at the time of surgery, where pCR is defined as the absence of residual invasive cancer and of DCIS (ypT0 ypN0) from breast tissue and sentinel/axillary lymph nodes, as assessed by central laboratory pCR at the time of surgery, defined as the absence of invasive cancer in breast tissue only (ypT0/is), as assessed by central laboratory)
- Evaluation of EFS(EFS up to end of study (EOS), defined as time from initial randomization to the date when disease recurrence or progression (local, regional, distant or contralateral) is diagnosed according to institutional standard, or date of death of any cause, whichever is earlier)
- Evaluation of overall response (OR) prior to surgery according to RECIST v1.1 criteria
- Evaluation of OS(OS: up to End of study, defined as time from the date of initial randomization to the date of death)
- Comparison of the safety profile of EG12014 and Herceptin during neoadjuvant treatment, and the safety of EG12014 and Herceptin during the entire study(Incidence of AEs (including severity, seriousness, and relationship to study drug) and laboratory abnormalities)
- Evaluation of the immunogenicity of EG12014 and Herceptin(Immunogenicity: Incidence and titer of ADA. Day 1 of Cycle 1 and 5 (neoadjuvant), Pre-surgery, Day 1 of cycles 1, 5, 9, 13 (adjuvant), and EOT)
- Comparison of EG12014 and Herceptin pharmacokinetics (PK) in the neoadjuvant setting(Serum trastuzumab concentration and/or population PK: Day 1 of Cycle 1, 5, 6, 7 and 8 (neoadjuvant), Pre-surgery (at 3 weeks after the last dose of neoadjuvant chemotherapy), Day 1 of cycles 1, 5, 9, 13 (adjuvant) and End of treatment)