ML29282-A PHASE IV, MULTICENTER, OPEN-LABEL, SINGLE-ARM STUDY OF PERTUZUMAB (IN COMBINATION WITH TRASTUZUMAB AND DOCETAXEL) IN FIRST LINE TREATMENT OF INDIAN PATIENTS WITH HER2-POSITIVE ADVANCED (METASTATIC OR LOCALLY RECURRENT) BREAST CANCER
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 52
- 试验地点
- 12
- 主要终点
- The primary outcome measures for this study are on safety evaluation
研究概览
简要总结
Thisis a Phase IV, single-arm, open-label, multicenter study to assess the safetyand efficacy of pertuzumab in combination with trastuzumab and docetaxel forthe treatment of patients with HER2-positive advanced (locally recurrent,unresectable, or metastatic) breast cancer. Patients must not have receivedsystemic non-hormonal anticancer therapy for their locally recurrent,unresectable, or metastatic disease.
The use of the combinationof pertuzumab with trastuzumab may be explained by their complementary mode ofaction, while pertuzumab prevents the ligand-activated formation of HER2heterodimers and homodimers, trastuzumab can block the shedding of HER2extracellular domain that would result in constitutively activated truncatedreceptors. Furthermore, as the two antibodies are not competing for the samebinding epitope on HER2, their combination may lead to a higher antibody load,resulting in increased tumor-cell killing via ADCC. A total of 52 patientswill be enrolled over duration of approximately 12 months.
Pertuzumab, trastuzumab, anddocetaxel chemotherapy will be administered in line with the PI. Docetaxeltreatment will be given at least for 6 treatment cycles; thereafter decisionfor continuation of docetaxel treatment will be based on investigator’sdiscretion.Patients will receive study medication till disease progression orunacceptable toxicity or withdrawal of consent or death, whichever occursfirst.All patients will be followed-up for at least 2 years after the lastpatient is enrolled; unless they have been lost to follow up, withdrawnconsent, or died, or the study has been prematurely terminated by theSponsor.Tumor assessments will be conducted every 9 weeks from the Day 1 offirst treatment cycle, i.e., every 3 cycles of monoclonal antibody treatment.Tumor assessments will be conducted during the follow-up period untilprogressive disease (PD) has been established, even if treatment has beendiscontinued due to unacceptable toxicity
研究设计
- 研究类型
- Interventional
- 分配方式
- Not Applicable
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- Female
入选标准
- •Male or female patients age ≥18 years
- •Signed, written informed consent (approved by the relevant Institutional Review Board [IRB]/Ethics Committee[EC]), prior to any study procedure
- •Histologically or cytologically confirmed and documented adenocarcinoma of the breast with metastatic or locally recurrent disease not amenable to curative resection; patients with measurable and/or non-measurable disease are eligible
- •Known and documented HER2-positive (defined as either immunohistochemistry [IHC] 3+ or in situ hybridization [ISH] positive) as assessed on primary tumor and/or metastatic site if primary tumor not available (ISH positivity is defined as a ratio of 2.0 or greater for the number of HER2 gene copies to the number of signals for CEP17, or for single probe tests,a HER2 gene count greater than 4) as determined in a local laboratory that is experienced/certified in HER2-expression testing using an accurate and validated assay
- •Known and documented LVEF of at least 50%
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- •A negative serum β-HCG test for women of childbearing potential (premenopausal, or <12 months of amenorrhea post-menopause, and women who have not undergone surgical sterilization [i.e., absence of ovaries and/or uterus]) within 7 days prior to the first dose of study treatment with the result available prior to first dosing
- •Contraception use must continue for the duration of study treatment and for at least 7 months after the last dose of study treatment.
- •Male patients whose partners are pregnant should use condoms for the duration of the pregnancy.
- •(for women of childbearing potential: agreement to remain abstinent (only if it is in line with the preferred and usual lifestyle) or use single or combined non-hormonal contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 7 months after the last dose of study drug)
- •Adequate organ function, as determined by the following laboratory results, within 3 days prior to study treatment: · Absolute neutrophil count >1,500 cells/mm3 · Platelet count >100,000 cells/mm3 · Hemoglobin >9 g/dL.
- •(patients may receive transfused red blood cells to obtain this level) · Albumin >2.5 g/dL · Total bilirubin ≤1.5 times the upper limit of normal (ULN), unless the patient has documented Gilbert’s syndrome · Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) >2.5 × ULN (>5 × ULN for patients with liver metastases) · Alkaline phosphatase (ALP) >2.5 × ULN (>5 × ULN in patients with liver metastases or >10 × ULN for patients with bone metastases) · Serum creatinine >2.0 mg/dL or 177 mmol/L · International normalized ratio (INR), activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) <1.5 × ULN (unless on therapeutic anti-coagulation).
排除标准
- •1.Previous systemic non-hormonal anticancer therapy for the metastatic or locally recurrent disease 2.Previous approved or investigative anti-HER2 agents in any breast cancer treatment setting, except trastuzumab and/or lapatinib in the adjuvant or neo-adjuvant setting 3.Disease progression while receiving or within 12 months of completion of trastuzumab and/or lapatinib treatment in the adjuvant or neo-adjuvant setting 4.History of persistent Grade 2 or higher (NCI-CTCAE, Version 4.03) hematologic toxicity resulting from previous adjuvant or neo-adjuvant therapy 5.Current, known peripheral neuropathy of Grade 3 or greater (NCI-CTCAE, Version 4.03) 6.History of other malignancy within the last 5 years prior to 1st study drug administration (dosing), except for carcinoma in situ of the cervix or basal cell carcinoma 7.Serious uncontrolled concomitant disease that would contraindicate the use of any drug used in this study or that would put the patient at high risk for treatment-related complications 8.Uncontrolled hypertension (systolic >150 mmHg and/or diastolic >100 mmHg) or clinically significant (i.e. active and/or requiring medication) cardiovascular disease, including but not limited to cerebrovascular accident (CVA)/stroke or myocardial infarction within 6 months prior to first study medication, unstable angina, CHF of New York Heart Association (NYHA) grade II or higher, or serious cardiac arrhythmia requiring medication, or other cardiovascular problem that is uncontrolled or is currently controlled with medication 9.Current known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) 10.Dyspnea at rest due to complications of advanced malignancy, or other disease requiring continuous oxygen therapy 11.Major surgical procedure or significant traumatic injury within 14 days prior to 1st study drug administration (dosing) or anticipation of need for major surgery during the course of study treatment 12.Known hypersensitivity to any of the study medications or to excipients of recombinant human or humanized antibodies 13.History of receiving any investigational treatment within 28 days prior to first study drug administration (dosing) and/or concurrent participation in any interventional clinical trial
- •Pregnant or lactating women
- •CNS Metastasis
- •LVEF decline to below 50 percentage.
结局指标
主要结局
The primary outcome measures for this study are on safety evaluation
时间窗: •Incidence and severity of AEs and serious adverse events (SAEs) by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 | •Incidence of congestive heart failure (CHF) and/or significant decline in LVEF | •LVEF over the course of the study | •Laboratory results abnormalities | •Incidence of AEs leading to discontinuation, modification, or interruption of study medication | •Incidence and cause of death due to AEs
次要结局
- The secondary outcome measures for this study are on efficacy evaluation(•Overall response rate (assessed by RECISTv1.1))