A Randomized, Open-label Phase III Trial to Evaluate the Efficacy and Safety of Pertuzumab Retreatment in Previously Pertuzumab, Trastuzuamb and Chemotherapy Treated Her2-Positive Metastatic Advanced Breast Cancer

Japan Breast Cancer Research Group3 个研究点分布在 1 个国家目标入组 226 人开始时间: 2015年8月1日最近更新: 2025年9月10日

适应症

干预措施

试验速览

阶段: 3 期
状态: 已完成
发起方: Japan Breast Cancer Research Group
入组人数: 226
试验地点: 3
主要终点: Progression-free survival (assessed by investigators)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The purpose of this study is to evaluate the efficacy and safety of pertuzumab, trastuzumab and chemotherapy as a pertuzumab retreatment compared to trastuzumab and chemotherapy in locally advanced or metastatic breast cancer patients for previously treated with pertuzumab

详细描述

The American Society of Clinical Oncology (ASCO) Clinical Practice Guidelines recommend the use of pertuzumab, trastuzumab and taxane as first-line treatment for patients with MBC. As a second-line treatment, trastuzumab emtansine (T-DM1) is also recommended. After a pertuzumab-containing regimen and T-DM1, other HER2-targeted therapeutic regimens, including lapatinib-containing regimens and trastuzumab plus chemotherapy, are recommended as third-line treatments and beyond. However, continual pertuzumab use for progression after a pertuzumab-containing regimen and retreatment with pertuzumab are unclear based on evidence.

The efficacy and the safety of two distinct modalities of a trastuzumab plus pertuzumab-containing regimen after pertuzumab use should be assessed in MBC: continual treatment and retreatment. However, it is clinically difficult to examine the efficacy of continual treatment with a trastuzumab plus pertuzumab-containing regimen because of several circumstances including the results of the MARIANNE study.

In addition, it is also important to evaluate the usefulness of retreatment with a pertuzumab-containing regimen. Continual pertuzumab treatment for progression after pertuzumab treatment is not same as pertuzumab retreatment. HER2-HER3-signaling suppressed by pertuzumab-containing regimens could potentially be restored by anti-HER2 therapy without pertuzumab. Pertuzumab retreatment could potentially re-suppress HER2-HER3-signaling. Therefore, Pertuzumab retreatment can be more effective than trastuzumab-containing treatment without pertuzumab.

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: None

入排标准

年龄范围: 20 Years 至 —（Adult, Older Adult）
性别: Female
接受健康志愿者: 否

入选标准

•Histologically or cytologically confirmed invasive breast cancer
•A confirmed HER2-positive status assessed by means of immunohistochemical analysis (with 3+ indicating positive status) and/or in situ hybridization (with an amplification ratio > 2.0 indicating positive) by each institute
•History of pertuzumab and trastuzumab-containing chemotherapy for locally advanced and metastatic breast cancer(2 or 3 regimen as previous chemotherapy regimen for locally advanced or metastatic breast cancer). The latest regimen before enrollment dose not include pertuzumab.
•Patients have measurable and/or non-measurable disease according to RECIST ver1.
•Female patients and aged ≥ 20 years.
•Left Ventricular Ejection Fraction (LVEF) > 50% at baseline (within 28 days before enrollment) as determined by either ECHO or MUGA
•Eastern Cooperative Oncology Group performance status of 0,1 or
•Life expectancy of patients is expected at least 3 months.
•Signed and written informed consent (approved by the Institutional Review Board or Independent Ethics Committee) is obtained before any study procedure.

排除标准

•History of chemotherapy > 4 regimen for locally advance or metastatic disease except for cancer chemotherapeutic agent-free treatment regimen (eg, hormonal therapy alone, combination with hormonal therapy and trastuzumab and anti-HER2 therapy alone).
•Persistent Grade >3 non-hematologic toxicity according to NCI-CTCAE v4.0-JCOG resulting from previous therapy at the time of enrollment.
•Symptomatic or uncontrolled central nervous system metastases.
•Multiple malignancies without history of breast cancer(within 10 years if invasive breast cancer and within 5 years if malignancies except invasive breast cancer)
•History of exposure to the following cumulative doses of anthracyclines:
•doxorubicin or liposomal doxorubicin > 360 mg/m2
•epirubicin > 720 mg/m2
•mitoxantrone > 100 mg/m2
•If more than 1 anthracycline has been used, then the cumulative dose must not exceed the equivalent of 360 mg/m2 of doxorubicin.
•Current uncontrolled hypertension (systolic > 150 mmHg and/or diastolic > 100 mmHg) or unstable angina.
•History of CHF of any New York Heart Association criteria, or serious cardiac arrhythmia requiring treatment (exception, atrial fibrillation, paroxysmal supraventricular tachycardia).
•History of myocardial infarction within 6 months of enrollment.
•Dyspnea at rest due to complications of advanced malignancy.
•Inadequate organ function, as determined by the following laboratory results, within 28 days before enrollment:
•Absolute neutrophil count < 1,500/mm3
•Platelet count < 100,000/mm3
•Hemoglobin < 8.0 g/dL
•Total bilirubin > 2.0 mg/dL, unless the patient has documented Gilbert's syndrome
•Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) > 100IU /L with the following exception (If considered that the liver dysfunction due to liver metastases > 200 IU/L, or 100 < , ≤200 IU/L with serum albumin < 2.5 g/dL)
•Serum creatinine value > 2.0 mg/dL or 177 μmol/L
•Current severe uncontrolled systemic disease(eg. Clinically significant cardiovascular, pulmonary and metabolic disease*, disorder of wound healing, ulcer and fracture)
•*If gemcitabine is planned to be selected as a combination chemotherapeutic agent,patients who has symptomatic interstitial pneumonia or pulmonary fibrosis on chest X-ray should be excluded.
•Uncontrolled malignancy-associated hypercalcemia syndrome under bisphosphonates or denosumab treatment.
•Radiation related grade >2 adverse event within 14 days before enrollment.
•Major surgical procedure or significant traumatic injury within 28 days before enrollment or anticipation of need for major surgery during the course of study treatment.
•Pregnant woman or positive pregnancy test.
•Nursing woman
•History of receiving any investigational treatment within 28 days before enrollment.
•Current known and active infection with human immunodeficiency virus, hepatitis B virus or hepatitis C virus.
•Receipt of intravenous antibiotics for infection within 14 days before enrollment.
•Current chronic daily treatment (continuous for > 3 months) with corticosteroids (dose equivalent to or greater than 10 mg/day methylprednisolone), excluding inhaled steroids.
•Known hypersensitivity to pertuzumab or trastuzumab without infusion reaction related to these drugs
•Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.

研究组 & 干预措施

Trastuzumab + chemotherapy

Active Comparator

Trastuzumab + chemotherapy Chemotherapy regimen is chosen from the following; Docetaxel, Paclitaxel, nab-paclitaxel ,Vinorelbine, Eribulin, Capecitabine or Gemcitabine

干预措施: Trastuzumab (Drug)

Trastuzumab + chemotherapy

Active Comparator

Trastuzumab + chemotherapy Chemotherapy regimen is chosen from the following; Docetaxel, Paclitaxel, nab-paclitaxel ,Vinorelbine, Eribulin, Capecitabine or Gemcitabine

干预措施: Docetaxel (Drug)

Trastuzumab + chemotherapy

Active Comparator

Trastuzumab + chemotherapy Chemotherapy regimen is chosen from the following; Docetaxel, Paclitaxel, nab-paclitaxel ,Vinorelbine, Eribulin, Capecitabine or Gemcitabine

干预措施: Paclitaxel (Drug)

Trastuzumab + chemotherapy

Active Comparator

Trastuzumab + chemotherapy Chemotherapy regimen is chosen from the following; Docetaxel, Paclitaxel, nab-paclitaxel ,Vinorelbine, Eribulin, Capecitabine or Gemcitabine

干预措施: Nab-paclitaxel (Drug)

Trastuzumab + chemotherapy

Active Comparator

Trastuzumab + chemotherapy Chemotherapy regimen is chosen from the following; Docetaxel, Paclitaxel, nab-paclitaxel ,Vinorelbine, Eribulin, Capecitabine or Gemcitabine

干预措施: Vinorelbine (Drug)

Trastuzumab + chemotherapy

Active Comparator

Trastuzumab + chemotherapy Chemotherapy regimen is chosen from the following; Docetaxel, Paclitaxel, nab-paclitaxel ,Vinorelbine, Eribulin, Capecitabine or Gemcitabine

干预措施: Eribulin (Drug)

Trastuzumab + chemotherapy

Active Comparator

Trastuzumab + chemotherapy Chemotherapy regimen is chosen from the following; Docetaxel, Paclitaxel, nab-paclitaxel ,Vinorelbine, Eribulin, Capecitabine or Gemcitabine

干预措施: Capecitabine (Drug)

Trastuzumab + chemotherapy

Active Comparator

Trastuzumab + chemotherapy Chemotherapy regimen is chosen from the following; Docetaxel, Paclitaxel, nab-paclitaxel ,Vinorelbine, Eribulin, Capecitabine or Gemcitabine

干预措施: Gemcitabine (Drug)