CTRI/2022/12/048133尚未招募3 期
Randomized, Double-Blind, Multicenter, Parallel Group, Clinical Trial to Compare Efficacy, Safety and Immunogenicity of Intas Pertuzumab with Perjeta® (In combination with Trastuzumab and Docetaxel) in Patients with HER2-Positive Metastatic Breast Cancer.
Intas Pharmaceuticals Ltd Biopharma Division27 个研究点 分布在 1 个国家目标入组 214 人开始时间: 2022年12月16日最近更新:
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 214
- 试验地点
- 27
- 主要终点
- To establish therapeutic equivalence between Intas Pertuzumab versus Perjeta (in combination with Trastuzumab and Docetaxel) in participants with HER2-positive metastatic breast cancer.
研究概览
简要总结
The primary objective of the trial is to demonstrate therapeutic equivalence of Intas pertuzumab with Perjeta with respect to Objective Response Rate (i.e., CR + PR; ORR) from baseline to 24 weeks by using Response Evaluation Criteria in Solid Tumors: Revised RECIST guideline (version 1.1). Rigorous criteria have been incorporated in the design of this therapeutic equivalence trial to properly assess the effect of the interventions on treatment outcome. In general, standardization of criteria, timing of assessments, procedures and interventions have been incorporated in the design of this trial to minimize variation.
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.Study participants must voluntarily provide written informed consent indicating that he or she understands the purpose of, and procedures required for the study and is willing to participate in the study.
- •2.Female participants must be 18 years and older of age, at the time of signing the informed consent.
- •3.Participants who are medically stable on the basis of physical examination, medical history, and 12-lead ECG performed at screening.
- •Any abnormalities, must be consistent with the underlying illness in the study population and this determination must be recorded in the participants source documents and initialed by the investigator.
- •4.Participants who are medically stable on the basis of clinical laboratory tests performed at screening.
- •If the results of the serum chemistry panel including liver enzymes, hematology, or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study.
- •This determination must be recorded in the participants source documents and initialed by the investigator.
- •5.Histologically or cytologically confirmed adenocarcinoma of the breast with the following: -Is locally recurrent or metastatic disease, and candidate for systemic chemotherapy -Is not amenable to resection with curative intent (curative surgery and/or radiation).-With at least one measurable lesion (based on RECIST criteria, version 1.1).Note: Particpants with de-novo Stage IV disease are eligible.
- •Bone and skin lesions, as well as lesions that were irradiated, biopsied or had any form of local intervention or surgical manipulation are only to be assessed as non-target lesions.
- •Baseline imaging scans must have been performed in the 4 weeks preceding randomization.
- •6.Documentation of HER2 gene amplification by fluorescent in situ hybridization (FISH); as defined by a ratio greater than 2.0) or documentation of HER2-overexpression by immunohistochemistry (IHC) (defined as IHC3 positive, or IHC2 positive with FISH confirmation) as assessed on primary tumor and/or metastatic site as determined in a local laboratory prior to randomization according to American Society of Clinical Oncology – College of American Pathologists (ASCO-CAP) guidelines.
- •7.Left Ventricular Ejection Fraction (LVEF) greater than or equal to 50 percent at baseline (within 42 days of randomization) as determined by either ECHO or MUGA.
- •History of LVEF decline to below 50 percent during or after prior trastuzumab adjuvant or neo-adjuvant therapy will not be eligible.Note: ECHO is the preferred method.
- •If the participant is randomized, the same method of LVEF assessment, ECHO or MUGA, must be used throughout the study, and to the extent possible, be obtained at the same institution.
- •8.Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 9.A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: -Is not a woman of childbearing potential (WOCBP) OR -Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of less than 1percent per year), with low user dependency when used consistently and correctly, as described in Appendix 10.4 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 at least 7 months after the last dose of study intervention.
- •The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.
- •A WOCBP must have a negative highly sensitive serum pregnancy test within 14 days and a negative urine pregnancy test within 2 days before the first dose of study intervention.
- •If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required.
- •In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.-Additional requirements for pregnancy testing during and after study intervention.-The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
排除标准
- •1.History of clinically significant liver or renal insufficiency clinically significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, metabolic disturbances, wound healing disorders, ulcers, or bone fractures as determined by the investigator.
- •2.Known allergies, hypersensitivity, or intolerance to study drugs or its excipients.
- •3.History of anticancer therapy for metastatic breast cancer or locally recurrent breast cancer (with the exception of one prior hormonal regimen for MBC).This includes any EGFR or anti-HER2 agents or vaccines, cytotoxic chemotherapy, or more than one prior hormonal regimen for MBC.
- •Note One prior hormonal regimen for MBC may include more than one hormonal therapy, for example, if the switch is not related to disease progression, such as toxicity or local standard practice, this will be counted as one regimen.
- •If a participant receives hormonal therapy for MBC and is switched to a different hormonal therapy due to disease progression, this will be counted as two regimens and the participant is not eligible.
- •4.History of approved or investigative tyrosine kinase/HER inhibitors for breast cancer in any treatment setting, except trastuzumab and or or lapatinib used in the neoadjuvant or adjuvant setting.
- •5.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 within 12 months.
- •6.History of persistent Grade greater than or equal 2 hematologic toxicity as per NCI-CTCAE, Version 5.0 resulting from previous adjuvant therapy.
- •7.Current peripheral neuropathy of NCI-CTCAE, Version 5.0, Grade greater than or equal 3 at screening.
- •8.Current clinical or radiographic evidence of central nervous system metastases.
- •Brain scan at screening or baseline is not mandatory.
- •In case of clinical suspicion brain scan can be performed based on investigator judgment.
- •9.History of exposure to the following cumulative doses of anthracyclines -doxorubicin or liposomal doxorubicin greater than 360 mg per m2 -epirubicin greater than 720 mg per m2 -mitoxantrone greater than 120 mg per m2 and idarubicin greater than 90 mg per m2 -Other (e.g., liposomal doxorubicin or other anthracycline greater than the equivalent of 360 mg per m2 of doxorubicin) -If more than 1 anthracycline has been used, then the cumulative dose must not exceed the equivalent of 360 mg per m2 of doxorubicin.
- •10.Current uncontrolled hypertension (systolic greater than 150 mmHg and or or diastolic greater than 100 mmHg).
- •11.Participant with known history or current symptoms of any of the following clinically significant cardiac conditions within the past 6 months prior to screening -Unstable angina or myocardial infarction -New York Heart Association (NYHA) functional classification for cardiac disease of Class II or greater -High-risk uncontrolled arrhythmias (i.e., atrial tachycardia with a heart rate greater than or equal to 100 per min at rest, significant ventricular arrhythmia [ventricular tachycardia], or higher-grade atrioventricular [AV]-block, such as second degree AV-block Type 2 (Mobitz 2) or third-degree AV-block).-Clinically significant pericardial disease -Electrocardiographic evidence of acute ischemic or active conduction system abnormalities-Any other cardiac illness that could lead to a safety risk to the participant,-Participants with known coronary artery disease, congestive heart failure not meeting the above criteria, must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate.
- •12.Current dyspnea at rest due to complications of advanced malignancy, or other diseases that require continuous oxygen therapy.
- •13.Any of the following abnormal investigational values -General Any laboratory abnormality which, in the opinion of the Investigator, would prevent the participant from safely completing the study or interfere with the interpretation of the study results.
- •Absolute neutrophils count less than or equal to 1500 per mm3 -Platelet count less than or equal to 100,000 per mm3 -Hemoglobin less than 9.0 g per dL (With no history of transfusion within the past 2 weeks) -Serum creatinine greater than 2.0 mg per dL and per or creatinine clearance by Cockroft-Gault formula less than 30 mL per min -Total bilirubin greater than or equal to 1.5 in to ULN (higher level greater than or equal to 3 in to ULN acceptable for Gilberts Syndrome) -Aspartate aminotransferase (AST) and or or alanine aminotransferase (ALT) greater than or equal to 2.5 in to ULN.
- •(Greater than or equal 5.0 in to ULN if liver metastases are present).
- •International normalized ratio (INR) and activated partial thromboplastin time or partial thromboplastin time (aPTT or PTT) greater than 1.5 in to ULN (unless on therapeutic coagulation) 14.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.
- •15.Receipt of IV antibiotics for infection within 14 days of randomization.
- •16.Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
- •17.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.
- •18.History of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening.
- •19.History of drug or alcohol abuse within 1 year before Screening.
- •20.Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years; carcinoma in situ of the cervix; or malignancy, which is considered cured with minimal risk of recurrence.
- •21.Received an investigational intervention (including investigational live vaccines) or used an invasive investigational medical device within 30 days or 5 half-lives prior to Baseline, whichever is longer, before the signing the consent.
结局指标
主要结局
To establish therapeutic equivalence between Intas Pertuzumab versus Perjeta (in combination with Trastuzumab and Docetaxel) in participants with HER2-positive metastatic breast cancer.
时间窗: To compare the independently assessed Objective Response Rate (i.e., CR plus PR) using Response Evaluation Criteria in Solid Tumours- Revised RECIST guideline (version 1.1) at Week 24.
次要结局
- To assess and compare efficacy of Intas Pertuzumab against Perjeta (in combination with Trastuzumab and Docetaxel) in participants with HER2-positive metastatic breast cancer.(Independently assessed clinical activity at Week 24 between treatment arms by measuring.)
- To compare first dose pharmacokinetics and trough level pharmacokinetics of Intas Pertuzumab and Perjeta in participants with HER2-positive metastatic breast cancer.(- To compare first dose pharmacokinetics of Intas pertuzumab against Perjeta.)
- To assess and compare safety, tolerability and immunogenicity of Intas Pertuzumab against Perjeta (in combination with Trastuzumab and Docetaxel) in participants with HER2-positive metastatic breast cancer.(- Incidence and titer of anti-drug antibodies over 24 week treatment duration.)
研究者
研究点 (27)
Loading locations...
相似试验
已完成
2 期
A Study to Evaluate the Effect of HER2 Activation on rhuMAb 2C4 (Pertuzumab) in Subjects With Advanced Ovarian CancerOvarian CancerNCT00058552Genentech, Inc.129
已完成
2 期
Safety and Effect of Pertuzumab in Patients With Advanced Non-Small Cell Lung Cancer, Which Has Progressed After Prior ChemotherapyNon-small Cell Lung CancerNCT00063154Genentech, Inc.51
招募中
2 期
DETERMINE Trial Treatment Arm 04: Trastuzumab in Combination With Pertuzumab in Adult, Paediatric and Teenage/Young Adult Patients With Cancers With HER2 Amplification or Activating MutationsLung NeoplasmColorectal NeoplasmsPancreatic NeoplasmNCT05786716Cancer Research UK30
已完成
3 期
Pertuzumab in Platinum-Resistant Low Human Epidermal Growth Factor Receptor 3 (HER3) Messenger Ribonucleic Acid (mRNA) Epithelial Ovarian Cancer (PENELOPE)Ovarian CancerNCT01684878Hoffmann-La Roche208
Unknown
2 期
Efficacy and Safety Study of Trastuzumab and Paclitaxel Based Regimens to Treat HER2-positive Breast CancerHER-2 Positive Breast CancerNCT01428414Zhimin Shao100