CTRI/2022/03/041271已完成3 期
A Prospective, Randomized, Multicenter, Comparative, Double-blind, Parallel study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Immunogenicity of Test Pertuzumab (ZRC-3277, Cadila Healthcare Ltd.,) with Reference Pertuzumab (Perjeta®, Genentech Inc.,) in Previously Untreated Patients with HER2 Positive Metastatic Breast Cancer.
Zydus Research Centre Cadila Healthcare Limited49 个研究点 分布在 1 个国家目标入组 268 人开始时间: 2022年9月26日最近更新:
适应症
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 268
- 试验地点
- 49
- 主要终点
- To compare the objective response rate (ORR) following Test Pertuzumab (Cadila
研究概览
简要总结
Breast cancer is the second most common cancer worldwide and the fifth cause of death from cancer overall (522,000 deaths) and it is the most frequent cause of cancer death in women in less developed regions.In developed countries between 6 and 10 % of women will have metastatic disease when diagnosed with breast cancer ; in developing countries this percentage can reach 60 %. Depending on initial stage, tumor biology, and type of treatment scheme received, between 30 and 50 % of women with early breast cancer will relapse.
Pertuzumab targets the extracellular dimerization domain (Subdomain II) of the human epidermal growth factor receptor 2 protein (HER2) and, thereby, blocks ligand-dependent heterodimerization of HER2 with other HER family members, including EGFR, HER3, and HER4. As a result, Pertuzumab inhibits ligand-initiated intracellular signaling through two major signal pathways, mitogen-activated protein (MAP) kinase, and phosphoinositide 3-kinase (PI3K). Inhibition of these signaling pathways can result in cell growth arrest and apoptosis, respectively. In addition, Pertuzumab mediates antibody-dependent cell-mediated cytotoxicity (ADCC).
Pertuzumab is a recombinant humanized monoclonal antibody that targets the extracellular 286 dimerization domain (Subdomain II) of the human epidermal growth factor receptor 2 protein 287 (HER2). Pertuzumab inhibits ligand-initiated intracellular signaling through two 299 major signal pathways, mitogen-activated protein (MAP) kinase and phosphoinositide 3-kinase 300 (PI3K).
Hence we have planned this study which is a Prospective, Randomized, Multicenter, Comparative, Double-blind, Parallel study to Evaluate the Efficacy and Safety of Test Pertuzumab (ZRC-3277, Cadila Healthcare Ltd.,) with Reference Pertuzumab (Perjeta®, Genentech Inc.,) in Previously Untreated Patients with HER2 Positive Metastatic Breast Cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant, Investigator, Outcome Assessor and Date-entry Operator 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
- •1.Female patients 18 to 65 years of age (both inclusive).
- •2.Patient with pathologically (histologically or cytologically) confirmed, adenocarcinoma metastatic breast cancer and candidate for chemotherapy.
- •Note: Patients with de-novo Stage IV disease are eligible.
- •3.With at least one measurable metastatic target lesion (based on RECIST criteria, version1.1).
- •4.Documentation of following prior to randomization: a)Documentation of HER2 gene amplification by fluorescent in situ hybridization (FISH); as defined by a ratio >2.0) OR documentation of HER2-overexpression by immunohistochemistry (IHC) (defined as IHC3+, or IHC2+ with FISH confirmation) (estrogen receptor/progesterone receptor positive subjects may be enrolled if they are HER2 positive) prior to randomization, see Section 6.4 for detailed criteria)
- •Eastern Co-operative Oncology Group (ECOG) performance status of 0 or
- •Left ventricular ejection fraction (LVEF) of ≥ 50% at baseline (within 42 days of randomization) as measured by echocardiography (ECHO) or multiple gated acquisition (MUGA).
- •Note: ECHO is the preferred method.
- •If the patient is randomized, the same method of LVEF assessment (i.e., ECHO or MUGA) must be used throughout the study and it should preferably be obtained at the same institution and preferably by the same assessor)
- •Patient able to understand and willing to give the informed consent and able to comply with the requirements of the study protocol.
- •A woman of childbearing potential must have a negative highly sensitive serum (β-human chorionic gonadotropin [β-hCG]) at screening and urine β-hCG test at randomization.
- •Woman of child-bearing potential must agree to use adequate contraceptive methods that is highly effective (with a failure rate of <1% per year), with low user dependency when used consistently and correctly, during the intervention period and for at least 7 months after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during the study and for a period of 7 months.
- •The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.
排除标准
- •History of anticancer therapy for MBC, with the exception of single prior hormonal regimen for MBC, which must be stopped prior to randomization.
- •Note 1: Anticancer therapy for MBC includes any epidermal growth factor receptor or anti- HER2 agents or vaccines, cytotoxic chemotherapy, or more than one prior hormonal regimen for MBC Note 2: Single prior hormonal regimen for MBC may include more than one hormonal therapy.If a patient is switched to a different hormonal therapy because of disease progression, this will be counted as two regimens, and the patient will not be eligible for the study.
- •If a patient is switched to a different hormonal therapy for reasons other than disease progression (e.g., toxicity or local standard practice), this will be counted as single regimen.
- •History of systemic breast cancer treatment in the neo-adjuvant or adjuvant setting with a disease-free interval from completion of the systemic treatment (excluding hormonal therapy) to metastatic diagnosis of < 12 months.
- •History of approved or investigative tyrosine kinase/HER inhibitors for breast cancer in any treatment setting, except trastuzumab used in the neoadjuvant or adjuvant setting.
- •Patients with CNS metastases, except for treated asymptomatic CNS metastases, provided all of the following criteria are met: a.
- •Only supra-tentorial metastases allowed (i.e., no metastases to midbrain, pons, medulla, or spinal cord) b.
- •No evidence of interim progression or hemorrhage after completion of CNS-directed therapy c.
- •No ongoing requirement for corticosteroids as therapy for CNS disease (anticonvulsants at a stable dose are allowed) d.
- •No stereotactic radiation within 14 days or whole-brain radiation within 28 days prior to randomization e.
- •Leptomeningeal disease (i.e. carcinomatous meningitis)
- •History of persistent Grade ≥ 2 hematologic toxicity resulting from previous neoadjuvant or adjuvant therapy (all grades based on National Cancer Institute Common Toxicity Criteria for Adverse Events, Version 5.0 [NCI CTCAE v 5.0]).
- •Current peripheral neuropathy of NCI-CTCAE, Version 5.0, Grade ≥ 3 at randomization.
- •Have a history of congestive heart failure (CHF) of any New York Heart Association (NYHA) criterion, or serious cardiac arrhythmia requiring treatment (except for atrial fibrillation,paroxysmal supraventricular tachycardia).
- •History of myocardial infarction within 6 months before randomization.
- •Current uncontrolled hypertension (systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg), or unstable angina.
- •History of other malignancy within the previous 5 years, except for carcinoma in situ of the cervix or non- melanoma skin carcinoma that has been previously treated with curative intent.
- •History of exposure to the following cumulative doses of anthracyclines: a.
- •doxorubicin or liposomal doxorubicin > 360 mg/m2 b.
- •epirubicin > 720 mg/m2 c.
- •mitoxantrone > 120 mg/m2 and idarubicin > 90 mg/m2 d.
- •Have a history of hypersensitivity to the Pertuzumab or to drugs with similar chemical structures, or to any of the excipients, or to murine proteins.
- •Have a history of severe hypersensitivity reaction to Trastuzumab and Docetaxel, or to any of the excipients.
- •Inadequate organ function, evidenced by the following laboratory results within 28 days prior to randomization: a.
- •Hemoglobin level < 9 g/dL b.
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels > 3.0 x upper limit of normal (ULN) (>5 x ULN in patients with liver metastases) c.
- •AST (SGOT) or ALT (SGPT) > 1.5 × ULN with concurrent serum alkaline phosphatase> 2.5 × ULN (unless bone metastases are present) d.
- •Absolute neutrophil count < 1,500 cells/mm3 e.
- •Total serum bilirubin >1.5 x ULN f.
- •Receipt of IV antibiotics for infection within 14 days of randomization.
- •Current chronic daily treatment with corticosteroids (dose of > 10 mg/day methylprednisolone equivalent) (excluding inhaled steroids).
- •History of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at Screening.
- •History of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening.
- •Pregnant or a nursing mother.
- •Major surgical procedure or significant traumatic injury within 28 days prior to study treatment start or anticipation of the need for major surgery during the course of study treatment.
- •Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; or bone fractures).
- •Have a history or suspicion of unreliability, poor cooperation or non-compliance with medical treatment or any other medical or psychiatric condition that could compromise study participation.
- •History of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-V) criteria within 1 year before Screening or positive test result(s) for alcohol or drugs of abuse (including barbiturates, opiates, cocaine, cannabinoids, amphetamines and benzodiazepines) at Screening.
- •Have any concurrent disease 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
To compare the objective response rate (ORR) following Test Pertuzumab (Cadila
时间窗: Baseline and Cycle 6
Healthcare Ltd.,) plus Trastuzumab and Docetaxel versus Reference Pertuzumab (Perjeta®,
时间窗: Baseline and Cycle 6
次要结局
- To assess the immunogenicity of Pertuzumab (Test Product, Cadila Healthcare Ltd.,) compared(to Reference Pertuzumab (Perjeta®, a product of Genentech, Inc.,).)
- To assess the pharmacokinetics of Pertuzumab (Test Product, Cadila Healthcare Ltd.,)(compared to Reference Pertuzumab (Perjeta®, a product of Genentech, Inc).)
- To assess the safety and tolerability of Pertuzumab (Test Product, Cadila Healthcare Ltd.,)(compared to reference Pertuzumab (Perjeta®, a product of Genentech, Inc).)
研究者
研究点 (49)
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