NCT06038539终止3 期
A Multicenter, Double-blind, Randomized, Parallel-group, Phase 3 Study to Compare the Efficacy and Safety of the Proposed Biosimilar PERT-IJS and EU-Perjeta® Along With Trastuzumab and Chemotherapy (Carboplatin and Docetaxel) as Neoadjuvant Treatment in Patients With Hormone Receptor Negative (HR-ve) Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Early Stage or Locally Advanced Breast Cancer
Biocon Biologics UK Ltd1 个研究点 分布在 1 个国家目标入组 55 人开始时间: 2025年1月6日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 55
- 试验地点
- 1
- 主要终点
- Efficacy endpoint - Total pathologic complete response between Treatment arm A and Treatment Arm B
研究概览
简要总结
To compare the efficacy and safety of PERT-IJS (Proposed biosimilar Pertuzumab) plus trastuzumab and chemotherapy (carboplatin and docetaxel) versus EU-Perjeta plus trastuzumab and chemotherapy (carboplatin and docetaxel) in neoadjuvant treatment of patients with HR-ve and HER-2 positive early stage or locally advanced breast cancer.
详细描述
This study is designed to compare the efficacy and safety of proposed biosimilar PERT-IJS plus trastuzumab, carboplatin and docetaxel versus EU-Perjeta plus trastuzumab, carboplatin and docetaxel in neoadjuvant treatment of HR-ve HER2-positive Early Breast Cancer (EBC) (invasive breast cancer without distant metastasis) or locally advanced breast cancer patients.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Patient willing and able to sign informed consent and to follow the protocol requirements
- •Female patients aged ≥ 18 years at the time of Screening
- •Patient with Eastern Cooperative Oncology Group (ECOG) Performance Status < 2
- •Patients with breast cancer that meets the following criteria:
- •A known case of histologically confirmed invasive breast carcinoma with a primary tumor size of > 2 cm by standard local assessment technique
- •stage at presentation: early stage (T2-3, N0-1, M0) or locally advanced (T2-3, N2 or N3, M0; T4a-c, any N, M0) or inflammatory (T4d, any N, M0)
- •Patients with HER2 overexpression by Immunohistochemistry (IHC) (defined as IHC 3+, or IHC 2+ with Fluorescence In Situ Hybridization (FISH) confirmation) as per the American Society of Clinical Oncology/College of American Pathologist (ASCO-CAP) guidelines prior to Screening and confirmed centrally before randomization
- •Patients with known HR-ve status (ER-negative and PR-negative) as per local laboratory prior to Screening and confirmed centrally before randomization
- •Patient willing to undergo mastectomy or breast-conserving surgery after neoadjuvant therapy
- •Patient who completes all necessary baseline laboratory and radiologic investigations prior to randomization as per Schedule of assessment (SoA)
- •Patient with baseline left ventricular ejection fraction (LVEF) ≥ 55% measured by echocardiography (ECHO; preferred) or multiple-gated acquisition (MUGA) scan
- •Patient is eligible to participant if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
排除标准
- •Patients with metastatic or recurrent bilateral breast cancer, or bilateral breast cancer
- •Patients with a history of concurrent or previously treated non-breast malignancies. A patient with previous invasive non-breast cancer is eligible provided she has been disease free for more than 5 years
- •Patients who have received any previous systemic therapy (including chemotherapy, immunotherapy, HER2-targeted agents, and antitumor vaccines) for treatment or prevention of breast cancer, or radiation therapy for treatment of cancer
- •Concurrent anti-cancer treatment in another investigational study, including hormone therapy or immunotherapy
- •Major surgical procedure that is unrelated to breast cancer within 4 weeks prior to randomization or from which the patient has not fully recovered
- •Serious cardiac illness or medical condition including but not limited to the following as per Investigator's discretion:
- •Patients with ≥ Class II stage of heart failure as per New York Heart Association Classification
- •High risk uncontrolled arrhythmia, such as atrial tachycardia with a heart rate > 100 bpm at rest, significant ventricular arrhythmia (e.g., ventricular tachycardia) required treatment, or higher-grade atrioventricular (AV) block (i.e., Mobitz II second-degree AV block or third-degree AV block)
- •History of myocardial infarction or unstable angina pectoris within 1 year of randomization or angina pectoris requiring anti-anginal medication
- •Evidence of transmural infarction on ECG
- •Clinically significant valvular heart disease
- •Poorly controlled hypertension (systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg) in patients on anti-hypertensive medications
- •Other concurrent serious diseases that may interfere with study primary endpoint and other study assessments, including, but not limited to, severe pulmonary conditions/illness, active liver disease (for example, active viral hepatitis infection [i.e., hepatitis B or hepatitis C]), autoimmune disorders, history of or known patient of sclerosing cholangitis, or infection with Human immune deficiency virus (HIV)
- •Patients with a history of any contraindication to the study treatment regimens
- •Any of the following abnormal laboratory test results prior to randomization:
- •Total bilirubin > upper limit of normal (ULN) or, for cases of known Gilbert's syndrome, total bilirubin > 2 × ULN
- •Aspartate aminotransferase and/or alanine aminotransferase > 1.5 × ULN, if considered clinically significant by Investigator
- •Alkaline phosphatase >2.5 × ULN, if considered clinically significant by Investigator
- •Serum creatinine > 1.5 × ULN
- •Creatinine clearance < 60 mL/min
- •Total white blood cells count < 2500 cells/μL
- •Absolute neutrophil count < 2000 cells/μL
- •Platelet count < 100,000 cells/μL
- •Participation in any clinical study with an investigational drug, biologic, or device within 1 month prior or within five half-lives (of the drug/ biologic) prior to the enrolment (whichever is longer)
- •Have taken any live vaccines 30 days prior to the 1st dose of study treatment
- •Any known hypersensitivity to any of the study medications, any of the ingredients or excipients of these medications, or benzyl alcohol
- •Patients unwilling to follow the study requirements.
- •Presence of an uncontrolled, unstable, clinically significant medical condition that, in the opinion of the Investigator, may interfere with the interpretation of efficacy and safety parameters or has a medical condition for which the treatment should take precedence over study participation or will interfere with study participation
研究组 & 干预措施
Treatment Arm A: PERT-IJS plus trastuzumab, carboplatin and docetaxel
Experimental
Part 1 (Cycle 1 to 6):
Initial loading dose of PERT-IJS is 840 mg administered as an approximately 60-minute IV infusion followed every 3 weeks by a maintenance dose of 420 mg administered as an IV infusion over a period of approximately 30 to 60 minutes.
Trastuzumab: Initial dose of trastuzumab is 8 mg/kg administered as approximately 90-minute IV infusion followed every 3 weeks by 6 mg/kg IV infusion over 30 to 90 minutes Carboplatin: Area Under the Curve (AUC) 6 for Cycles 1 to 6 Docetaxel: 75 mg/m2 by IV infusion every 3 weeks for Cycles 1 to 6
Part 2 (Cycle 7 - till end of 1 year from Cycle 1 day 1):
Initial loading dose of PERT-IJS is 840 mg administered as approximately 60-minute IV infusion followed every 3 weeks by a maintenance dose of 420 mg administered as an IV infusion over a period of approximately 30 to 60 minutes.
Trastuzumab: As mentioned in part 1
干预措施: PERT-IJS plus trastuzumab, carboplatin and docetaxel (Biological)
Treatment Arm B: EU-Perjeta plus trastuzumab, carboplatin and docetaxel
Active Comparator
Part 1 (Cycle 1 to 6):
Initial loading dose of EU- Perjeta is 840 mg administered as approximately 60-minute IV infusion followed every 3 weeks by a maintenance dose of 420 mg administered as an IV infusion over a period of approximately 30 to 60 minutes.
Trastuzumab: Initial dose of trastuzumab is 8 mg/kg administered as approximately 90-minute IV infusion followed every 3 weeks by 6 mg/kg IV infusion over 30 to 90 minutes Carboplatin: Area under the curve 6 for Cycles 1 to 6 Docetaxel: 75 mg/m2 by IV infusion every 3 weeks for Cycles 1 to 6
Part 2 (Cycle 7 onwards till end of 01 year from Cycle 1 day 1):
The patients will be re-randomized (1:1) to receive EU- Perjeta + trastuzumab or PERT-IJS + trastuzumab.
Initial loading dose of PERT-IJS is 840 mg administered as approximately 60-minute IV infusion followed every 3 weeks by a maintenance dose of 420 mg administered as an IV infusion over a period of approximately 30 to 60 minutes.
Trastuzumab: As mentioned in part 1
干预措施: Perjeta plus trastuzumab, carboplatin and docetaxel (Biological)
结局指标
主要结局
Efficacy endpoint - Total pathologic complete response between Treatment arm A and Treatment Arm B
时间窗: Week 18
Total pathologic complete response (tpCR; ypT0/Tis,ypN0) in breast and axillary nodes after neoadjuvant treatment by Independent Review Committee (IRC)
次要结局
- Efficacy endpoint-Total pathologic complete response between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen(Week 18)
- Efficacy endpoint: Pathologic complete response between Treatment Arm A and Treatment Arm B(Week 18)
- Efficacy endpoint-Event free survival rate between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen(Week 18)
- Efficacy endpoint- Overall survival rate between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen(Week 18)
- Efficacy Endpoint: EFS rate after the single switch from EU-Perjeta to PERT-IJS+trastuzumab compared with those continuing on Treatment B(1 year)
- Efficacy Endpoint: Disease free survival rate after the single switch from from EU-Perjeta to PERT-IJS+trastuzumab compared with those continuing on EU-Perjeta+trastuzumab(1 year)
- Efficacy endpoint- Breast pathologic complete response between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen(Week 18)
- Efficacy endpoint-Objective response rate between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen(Week 18)
- Efficacy endpoint-EFS rate of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout(1 Year)
- Efficacy endpoint - Overall Survival rate of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout(1 Year)
- Efficacy endpoint - Overall Response Rate of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout(1 Year)
- Efficacy Endpoint: Overall survival rate after the single switch from from EU-Perjeta to PERT-IJS+trastuzumab compared with those continuing on EU-Perjeta+trastuzumab(1 year)
- Pharmacokinetic (PK) endpoint-The trough serum concentration(1 Year)
- Safety Endpoint: treatment-emergent adverse events and serious adverse events(week 18)
- Safety Endpoint: left ventricular ejection fraction(week 18)
- Safety Endpoint: Vital signs(week 18)
- Safety Endpoint-ECG PR Interval(week 18)
- Safety Endpoint-ECG QRS Interval(week 18)
- Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout- ECG PR Interval(1 year)
- Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout-ECG QRS Interval(1 year)
- Safety Endpoint: treatment-emergent adverse events and serious adverse events of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta(1 year)
- Safety Endpoint: left ventricular ejection fraction of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout(1 year)
- Safety Endpoint-physical examination(week 18)
- Safety Endpoint-ECG QT Interval(week 18)
- Safety Endpoint- ECG corrected QT interval (QTc) Interval(week 18)
- Safety Endpoint-clinical laboratory assessments(week 18)
- Safety Endpoint-pregnancy test(week 18)
- Immunogenicity Endpoint(week 18)
- Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS -throughout compared to patients randomized to EU-Perjeta throughout- Vital signs(1 year)
- Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout-ECG QT Interval(1 year)
- Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout- ECG QTc Interval(1 year)
- Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout-Clinical laboratory assessments(1 year)
- Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout- Pregnancy test(1 year)
- Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout-Physical examination(1 year)
- Immunogenicity Endpoint of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout(1 year)
- Safety Endpoint: Incidence of TEAEs and SAEs after the single switch from EU-Perjeta to PERT-IJS+trastuzumab versus those continuing on EU-Perjeta+trastuzumab throughout(1 Year)
- Immunogenicity End Point: after the single switch from EU-Perjeta to PERT-IJS+trastuzumab versus those continuing on EU-Perjeta+trastuzumab(1 Year)
- Safety End Point :left ventricular ejection fraction incidences after the single switch from EU-Perjeta to PERT-IJS+trastuzumab versus those continuing on EU-Perjeta+trastuzumab(1 year)
研究者
研究点 (1)
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