Multicenter randomized double blind phase III clinical trial comparing safety and efficacy of BCD-022 (CJSC BIOCAD, Russia) used with paclitaxel to Herceptin® (F. Hoffmann-La Roche Ltd, Switzerland) used with paclitaxel in the first-line treatment of HER2-positive metastatic breast cancer patients.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 206
- 试验地点
- 22
- 主要终点
- The therapy efficacy will be evaluated using contrast-enhanced computed tomography (CT) data. The efficacy analysis will include all randomized evaluable patients (ITT – intent-to-treat analysis). Contrast-enhanced CT will be performed at screening, after 3 therapy cycles (21±3 days after 3rd administration of investigational product) and after 6 therapy cycles (21±3 days after 6th administration of investigational product).
研究概览
简要总结
It is Multicenter randomized double-blind phaseIII clinical trial comparing safety and efficacy of BCD-022 (CJSC BIOCAD,Russia) used with paclitaxel to Herceptin®(F. Hoffmann-LaRoche Ltd, Switzerland) used with paclitaxel in the first-line treatment ofHER2-positive metastatic breast cancer patients.The main objective of the studyis to evaluate overall response rate and other efficacy parameters,Incident and severity of adverse events, determination of Serum concentrationof trastuzumab after the first administration and incidence and concentration of anti-trastuzumabantibodies in patients with HER2(+) mBC treated with BCD-022 or Herceptin® administered in combination with paclitaxel. 40 patientswith HER2-positivemetastatic breast cancer will be recrited into the study. After signing theinformed consent and completing screening procedures, patients will bestratified and randomly assigned (randomized) to receive BCD-022 and paclitaxel or Herceptin®andpaclitaxel in 1:1 ratio.The study will be conducted at 18 sites of India.
Trastuzumab is a humanized monoclonalantibody (mAb), specific to HER2 extracellular domain. Number of randomizedclinical studies showed that trastuzumab in combination with or followed by adjuvantchemotherapy significantly increases treatment efficacy in patients with earlystage BC. Trastuzumab in patients with HER2+ BC reduces relapse rate byapproximately 2 folds and mortality – by one third. According to these data, trastuzumab was approved as therapystandard for early stages HER2+ BC. Trastuzumab addition to the therapy ofmetastatic BC and metastatic GC also increases therapy efficacy.CJSC BIOCAD hasdeveloped a trastuzumab which is a full equivalent (biosimilar) of Herceptin®.The full cycle of biosimilar trastuzumab production is localized in Russia.Preclinical studies of trastuzumab manufactured by CJSC BIOCAD show that itspharmacokinetics and toxicity are equivalent to those of Herceptin®.Studies conducted on primates showed no significant differences in CJSC BIOCADtrastuzumab and Herceptin®safety parameters. Multicenter double-blind randomized clinicalstudy of BCD-022 (CJSC BIOCAD, Russia) and Herceptin® (F.Hoffmann-LaRoche., Switzerland) showed that safety and pharmacokinetic profiles of thesedrugs were equivalent when used in combination with paclitaxel in mBC HER2+patients. Consequently, BCD-022 can be recommended for further clinical studyof safety and efficacy in this population.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 75.00 Year(s)（—）
- 性别
- Female
入选标准
- •1.Written informed consent and ability to follow the Protocol procedures; 2.Age18 years and age 75 years; 3.Female gender; 4.Histologically confirmed breast cancer (BC); 5.Metastatic BC (stage IV according to TNM classification version 6); 6.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) ; 7.Documented results of oestrogen and progesterone receptors expression analysis; 8.ECOG status 0, 1 or 2, not increasing within 2 weeks prior to randomization; 9.Life expectancy – 20 weeks or more from the moment of randomization; 10.Presence of at least 1 tumour lesion with a size not less than 1 cm (revealed with CT slice thickness not more than 5 mm).
- •Patients having bone metastasis as the only measurable tumour lesion are not eligible for the trial; 11.Patients of childbearing potential 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 cytotoxic chemotherapy, or 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 hormonal therapy is allowed;
- •Disease progression within 6 months after adjuvant and/or neoadjuvant BC therapy.
- •Surgery, radiation therapy, hormonal therapy, use of any experimental medications within 4 weeks (28 days) prior to randomization.
- •Hypersensitivity to paclitaxel and all medications containing polyoxyethylated castor oil, hypersensitivity to dexamethasone, diphenhydramine, ranitidine/cimetidine, recombinant murine proteins, contrast agents or excipients of study medications;
- •BC metastases in CNS, progressing or clinically manifested (e.g. cerebral oedema, spinal cord injury), with exception of non-progressing metastases not requiring treatment with glucocorticosteroids and/or anticonvulsants within 4 weeks prior to randomization;
- •Cardiovascular system pathology (CHF stage III-IV according to NYHA classification, unstable angina pectoris, myocardial infarction) within 12 months prior to randomization;
- •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);
- •Left ventricular ejection fraction <50% according to ECG;
- •Neutrophils ≤1500/mm3;
- •Platelets ≤100 000/mm3;
- •Hemoglobin ≤90 g/L;
- •Creatinine level ≥ 1.5 × upper limit of normal (ULN);
- •Bilirubin level ≥ 1.5 × ULN;
- •AST and ALT levels ≥ 2.5 × ULN (5 × ULN for patients with liver metastases);
- •Alkaline phosphatase level ≥ 5 × ULN;
- •Pregnancy or lactation;
- •Any other concomitant cancer including contralateral breast cancer revealed within 5 years prior to screening, except curatively treated intraductal carcinoma in situ, curatively treated cervical carcinoma in situ or curatively treated basal cell or squamous cell carcinoma;
- •Conditions limiting patient’s adherence to protocol requirements (dementia, neurologic or psychiatric disorders, drug addiction, alcoholism and others);
- •Stage II-IV neuropathy according to CTCAE v.4.0;
- •Concomitant participation in other clinical trials, previous participation in other clinical trials within 30 days before entering into the trial, previous participation in the same trial;
- •Acute or active chronic infections;
- •Obstacles in intravenous administration of study drugs.
结局指标
主要结局
The therapy efficacy will be evaluated using contrast-enhanced computed tomography (CT) data. The efficacy analysis will include all randomized evaluable patients (ITT – intent-to-treat analysis). Contrast-enhanced CT will be performed at screening, after 3 therapy cycles (21±3 days after 3rd administration of investigational product) and after 6 therapy cycles (21±3 days after 6th administration of investigational product).
时间窗: As defined in protocol
次要结局
- •Saftey and efficacy evaluation.(•AE incidence in both groups.)