Randomized, Single-blind, Multicenter, Parallel Group Clinical Trial to Assess Pharmacokinetic Parameters, 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
- 1 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Pharmacokinetic parameters: AUC0-t
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 50 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.
Primary endpoint is serum peak concentrations (Cmax), area under the curve from 0 to t (AUC0-t).
This trial is intended to assess the biosimilarity of pharmacokinetic parameters, safety between Faceptor (experimental drug) and Herceptin (reference).
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
Pharmacokinetic parameters: AUC0-t
时间窗: Blood samples will be collected at following time points: prior to IP administration; 1.5; 3; 4.5; 6; 24; 96; 168; 336 and 504 hours after inject drug cycle 1
Area under the curve from 0 to t (AUC0-t)
Pharmacokinetic parameters: Cmax
时间窗: Blood samples will be collected at following time points: prior to IP administration; 1.5; 3; 4.5; 6; 24; 96; 168; 336 and 504 hours after inject drug cycle 1
Serum peak concentrations (Cmax)
次要结局
- Pharmacokinetic parameters: Ctrough(Blood samples will be collected at following time points: day 23rd, 65th, 107th and 128th (at the beginning of visits 4, 8, 12, 14))
- Pharmacokinetic parameters: AUC0-∞(Blood samples will be collected at following time points: prior to IP administration; 1.5; 3; 4.5; 6; 24; 96; 168; 336 and 504 hours after inject drug cycle 1)
- Pharmacokinetic parameters: Tmax(Blood samples will be collected at following time points: prior to IP administration; 1.5; 3; 4.5; 6; 24; 96; 168; 336 and 504 hours after inject drug cycle 1)
- Pharmacokinetic parameters: T1/2(Blood samples will be collected at following time points: prior to IP administration; 1.5; 3; 4.5; 6; 24; 96; 168; 336 and 504 hours after inject drug cycle 1)
- Rate of AE and SAE occurence(up to 128 days (6 cycles - each cycle is 21 days))