Randomized, Single-blind, Multicenter, Parallel Group Clinical Trial to Assess Efficacy and Safety of NNG-TMAB (Trastuzumab) in Combination With Docetaxel on Recurrent or Metastatic Breast Cancer Patients With Positive HER2
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 128
- 试验地点
- 2
- 主要终点
- Overall Response Rate (ORR) according to RECIST 1.1 after 6 cycles
研究概览
简要总结
Targeted therapy in the treatment of breast cancer targets HER2 receptor (Human Epidermal growth factor Receptor). HER2 receptor plays an important role in cell growth and differentiation (5). However, when HER2 overexpresses, it may lead to cancer. HER2 positive malignance exacerbates pathology and worsens clinical outcome, such as shortened overall survival (OS) compared with non-HER2 overexpression patients (6), (7). About 20-30% overexpression HER2/neogene breast cancer patients and patients having HER2 overexpression tumor have disease progression and poor prognosis in metastatic process (8), (9).
Currently, targeted therapeutic, which attaches to the HER2 receptor, inhibiting the growth of cancer cells has been approved. One of these products is Trastuzumab.
The study processed on 128 females aged between 18 and 65, recurrent or metastatic breast cancer patients with positive HER2.
The subjects were randomly distributed in 2 groups as NNG-TMAB + docetaxel or Herceptin® + docetaxel, in blocks of 4 in a 1: 1 ratio (NNG-TMAB: Herceptin®). In each block of 4 will be 2 patients in the experimental group and 2 patients in the control group
Primany endpoints is Overall Response Rate (ORR) according to RECIST 1.1. ORR includes Complete Response Rate and Partial Response Rate. ORR will be independently evaluated by an Independent Tumor Evaluation Board (ITEB).
This trial is intended to assess the biosimilarity of efficacy and safety between NNG-TMAB (Trastuzumab) and Herceptin® in combination with Docetaxel on recurrent or metastatic breast cancer patients with positive HER2.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female patients from 18 to 65 years old.
- •Willing to give written and signed informed consent.
- •Have pathologically or cytologically confirmed breast cancer.
- •Inoperable, recurrent or metastatic breast cancer according to TNM classification and investigator' s assessment.
- •Presence of at least 1 tumour with a size not less than 1 cm (revealed with computed tomography (CT) slice thickness not more than 5 mm). Patients having bone metastasis as the only measurable tumour are not eligible for the trial.
- •Grade 3+ HER2 overexpression confirmed by immunohistochemical (IHC) staining or grade 2+ HER2 overexpression accompanied by HER2 gene amplification confirmed by fluorescent hybridization in situ (FISH).
- •Eastern Cooperative oncology group performance status ≤ 2
- •Willing to comply the requirements of the study protocol.
- •Have a survival expectancy of at least 6 months.
- •At screening period: Hb ≥ 9 g/dL; Neutrophils ≥ 1,5x10^9/L; platelets ≥ 100x10^9/L; creatinine level ≤ 1,5 x upper limit of normal (ULN); bilirubin level < 1,5 x ULN; ALT/AST < 2,5 x ULN (< 5 x ULN for patients with liver metastases), ALP < 5 x ULN.
- •Patients of childbearing potential and her partner must implement reliable contraceptive measures during the study treatment, starting 4 weeks prior to inclusion into the trial and until 6 months after the last administration of the study drug
排除标准
- •Previous anticancer therapy for metastatic BC, including previous anticancer therapy with signal transduction inhibitors (e.g. lapatinib), biological drugs (e.g. trastuzumab, bevacizumab), experimental (not approved for BC therapy) anticancer drugs. Any previous chemotherapy or hormonal therapy is allowed.
- •Previously treated with doxorubicin > 400 mg/m2; epirubicin > 800 mg/m2 in accumulative dosages.
- •Surgery, radiation therapy, use of any experimental medications within 4 weeks prior to randomization.
- •Clinical evidence or X-ray show that breast cancer metastases in central nervous system
- •Patients with metastatic tumor to the bone is the only tumor to be measured
- •Systolic blood pressure >150mmHg and/or diastolic blood pressure >100mmHg. Uncontrolled hypertension comprising all cases of arterial hypertension when no decrease in blood pressure could be achieved despite treatment with a combination of 3 antihypertensive drugs including one diuretic and non-medicamental correction methods (low salt diet, physical exercise)
- •Cardiovascular system pathology (congestive heart failure (CHF) stage III-IV according to New York Heart Association (NYHA) classification, unstable angina pectoris, myocardial infarction) within 12 months prior to randomization. LVEF < 50% according to echocardiogram when screening.
- •Acute or chronic infection (except for acute or chronic infection that is stable and does not affect the study evaluation). Infecting HIV, HBV or HCV, Syphilis
- •Patients with a history of severe allergic reaction to trastuzumab, paclitaxel, docetaxel or other ingredients in the formulation
- •The patient has evidence of a serious illness (such as resting dyspnea or severe lung disease, etc.) or an abnormal laboratory test that, in the judgment of the researcher, will affect participation. research and completion of patient research, or may affect the patient's response evaluation.
- •Pregnancy, intend to get pregnant, lactation
研究组 & 干预措施
Faceptor + Docetacel
Patients received a loading dose of Faceptor 8 mg/kg IV + docetaxel 75 mg/m^2 IV on Cycle 1 followed by Faceptor 6 mg/kg IV + docetaxel 75 mg/m^2 IV on the next 5 cycles (each cycle is 21 days)
干预措施: Faceptor (Drug)
Faceptor + Docetacel
Patients received a loading dose of Faceptor 8 mg/kg IV + docetaxel 75 mg/m^2 IV on Cycle 1 followed by Faceptor 6 mg/kg IV + docetaxel 75 mg/m^2 IV on the next 5 cycles (each cycle is 21 days)
干预措施: Docetaxel (Drug)
Herceptin + Docetacel
Patients received a loading dose of Herceptin 8 mg/kg IV + docetaxel 75 mg/m^2 IV on Cycle 1 followed by Herceptin 6 mg/kg IV + docetaxel 75 mg/m^2 IV on the next 5 cycles (each cycle is 21 days)
干预措施: Herceptin (Drug)
Herceptin + Docetacel
Patients received a loading dose of Herceptin 8 mg/kg IV + docetaxel 75 mg/m^2 IV on Cycle 1 followed by Herceptin 6 mg/kg IV + docetaxel 75 mg/m^2 IV on the next 5 cycles (each cycle is 21 days)
干预措施: Docetaxel (Drug)
结局指标
主要结局
Overall Response Rate (ORR) according to RECIST 1.1 after 6 cycles
时间窗: at the end of cycle 6 (each cycle is 21 days)
ORR includes Complete Response Rate and Partial Response Rate. ORR will be independently evaluated by an Independent Tumor Evaluation Board (ITEB).
Overall Response Rate (ORR) according to RECIST 1.1 at the end of study
时间窗: baseline through end of study (up to 128 days)
ORR includes Complete Response Rate and Partial Response Rate. ORR will be independently evaluated by an Independent Tumor Evaluation Board (ITEB).
次要结局
- Progressive Disease Rate (PDR) according to RECIST 1.1(PDR will be evaluated every 3 cycles (each cycle is 21 days) through the end of study (up to 128 days))
- Stable Disease Rate (SDR) according to RECIST 1.1(SDR will be evaluated every 3 cycles (each cycle is 21 days) through the end of study (up to 128 days))
- Progression-free survival (PFS) according to RECIST 1.1(Baseline up to disease progression or death due to any cause, whichever occurs first (up to 128 days (6 cycles - each cycle is 21 days)))
- Evaluate the patient's quality of life(At week 24th)
- Anti-drug antibody evaluation(At baseline,after 3 cycles of treatment, after 6 cycles of treatment (each cycle is 21 days))
- Rate of AE and SAE occurence(up to 128 days (6 cycles - each cycle is 21 days))