Phase II Prospective Open Label Study of Pertuzumab, Trastuzumab, and Nab-Paclitaxel in Patients With HER-2 Positive Advanced Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 63
- 试验地点
- 3
- 主要终点
- Progression Free Survival (MBC Cohort)
研究概览
简要总结
This phase II trial studies how well pertuzumab, trastuzumab, and paclitaxel albumin-stabilized nanoparticle formulation work in treating patients with human epidermal growth factor receptor (HER) 2-positive stage II-IV breast cancer. Monoclonal antibodies, such as pertuzumab and trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to kill tumor cells or stop them from growing. Giving pertuzumab and trastuzumab together with paclitaxel albumin-stabilized nanoparticle formulation may be a better way to block tumor growth.
详细描述
PRIMARY OBJECTIVES:
I. To determine efficacy of administration of pertuzumab in combination with trastuzumab with nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation) in subjects with stage IV human epidermal growth factor receptor (HER)-2 overexpressing metastatic breast cancer (MBC) as measured by progression free survival (PFS).
II. To determine the efficacy as neoadjuvant treatment of the regimen in HER2+ locally advanced breast cancer (LABC) as defined by pathologic complete response (pCR).
SECONDARY OBJECTIVES:
I. To evaluate the safety of pertuzumab when added to trastuzumab and nab-paclitaxel in HER-2 overexpressing MBC and LABC cancer as assessed by the frequency and severity of adverse events (AEs), abnormal findings on physical examination, laboratory tests, and vital signs.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Patients must be diagnosed with metastatic cytologically or histologically confirmed adenocarcinoma of the breast with HER2 over-expression or with newly diagnosed locally advanced (including inflammatory) breast cancer (LABC) with stage II-III disease; patients with metastatic (stage IV) disease (MBC) must have measurable lesions
- •Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
- •Tumor positive or negative for expression of hormone receptors (< 1% or > 1%) and overexpressing HER2 by immunohistochemistry (IHC) (3+), or, HER2-amplified by fluorescence in situ hybridization (FISH) or by alternative gene testing
- •For patients with LABC, no prior therapy is allowed
- •For patients with MBC, prior adjuvant chemotherapy and trastuzumab more than or equal to 12 months prior to enrollment are allowed
- •No prior chemotherapy or trastuzumab for treatment of metastatic breast cancer
- •Left ventricular ejection fraction (LVEF) >= 50% (determined by echocardiogram or multigated acquisition scan) within 42 days of treatment
- •Eastern Cooperative Oncology Group performance status of 0 or 1
- •Hemoglobin >= 9 g/dl
- •Leukocytes >= 3.0 x 10^9/L
- •Absolute neutrophil count >= 1.5 x 10^9/L
- •Platelets >= 100 x 10^9/L
- •Total bilirubin =< 1.3 mg/dl (institutional upper limit of normal)
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2 x institutional upper limit of normal
- •Creatinine within normal institutional limits or creatinine clearance > 50 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal (using Cockcroft-Gault formula)
- •All radiology studies (study requiring staging) must be performed within 35 days prior to the start of therapy
- •No serious medical conditions such as myocardial infarction within 6 months prior to entry, congestive heart failure, unstable ventricular arrhythmia, uncontrolled hypertension, uncontrolled diabetes mellitus, uncontrolled psychotic disorders, serious infections, active peptic ulcer disease, psychiatric illness, or any other medical conditions that might be aggravated by treatment or limit compliance
- •Currently, no active second malignancy other than non-melanoma skin cancer; note: patients are not considered to have a "current active" malignancy if they have completed anti-cancer therapy and are considered by their physicians to have a less than 30% chance of relapse
- •All patients must have the ability to understand and the willingness to sign an informed consent
- •Negative serum or urine beta-human chorionic gonadotropin (hCG) pregnancy test at screening for patients of child-bearing potential
- •No prior therapies (except for anti-estrogen therapy) are allowed for the treatment of the newly diagnosed metastatic breast cancer; patients are allowed to have had prior chemotherapy for breast cancer in the adjuvant setting for at least 12 months prior to enrollment into this study; patients with a prior diagnosis of malignancy treated >= 5 years ago are eligible, provided that they have not received prior nab-paclitaxel as part of their prior treatment regimen, and that they meet all eligibility criteria
排除标准
- •Known active hepatitis B or C
- •Known active human immunodeficiency virus (HIV)
- •Prior breast cancer or other invasive malignancy treated within 5 years
- •Pregnancy
- •Neuropathy > grade 1
- •Any other intercurrent medical/psychological problem deemed exclusionary by the treating physician or investigators/principal investigator (PI)
- •Cumulative dose of doxorubicin or equivalent of > 360 mg/m^2 during prior adjuvant therapy
- •LVEF < 50% during previous trastuzumab therapy
- •Central nervous system metastases
- •Another malignancy excluding basal cell skin cancer
- •Pregnant women
- •Subjects will be excluded who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
研究组 & 干预措施
Treatment (pertuzumab, trastuzumab, nab-paclitaxel)
Patients receive pertuzumab IV over 30-60 minutes on day 1, trastuzumab IV over 30-90 minutes and paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
Treatment (pertuzumab, trastuzumab, nab-paclitaxel)
Patients receive pertuzumab IV over 30-60 minutes on day 1, trastuzumab IV over 30-90 minutes and paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: paclitaxel albumin-stabilized nanoparticle formulation (Drug)
Treatment (pertuzumab, trastuzumab, nab-paclitaxel)
Patients receive pertuzumab IV over 30-60 minutes on day 1, trastuzumab IV over 30-90 minutes and paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: trastuzumab (Biological)
Treatment (pertuzumab, trastuzumab, nab-paclitaxel)
Patients receive pertuzumab IV over 30-60 minutes on day 1, trastuzumab IV over 30-90 minutes and paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: pertuzumab (Biological)
结局指标
主要结局
Progression Free Survival (MBC Cohort)
时间窗: assessed up to 5 years
Estimated using the product-limit method of Kaplan and Meier. From time of initial treatment until disease progression or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Five Year Disease-free Survival (LABC Cohort)
时间窗: assessed up to 5 years
Estimated using the method of Kaplan-Meier. Disease-free survival is defined as the time from Initial treatment to recurrence of tumor or death
次要结局
- Overall Response (MBC Cohort)(Up to 5 years)
- Five Year Overall Survival(Assessed up to 5 years)