NCT03414658进行中（未招募）2 期
A Randomized, Phase II Study Comparing Trastuzumab and Vinorelbine in Combination With Avelumab or Avelumab and Utomilumab (41BB/CD137 Agonist), in Patients With HER2-positive Metastatic Breast Cancer Who Have Progressed on Prior Trastuzumab and Pertuzumab
Adrienne G. Waks21 个研究点 分布在 1 个国家目标入组 100 人开始时间: 2018年6月21日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 100
- 试验地点
- 21
- 主要终点
- Progression Free Survival
研究概览
简要总结
This research study is studying a combination of drugs as a possible treatment for breast cancer.
The drugs involved in this study are:
- Group A: Trastuzumab (Herceptin) + Vinorelbine (Navelbine)
- Group B: Trastuzumab + Vinorelbine + Avelumab
- Group C: Trastuzumab + Vinorelbine + Avelumab + Utomilumab (PF-05082566)
详细描述
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug combination to learn whether the drug combination works in treating a specific disease. "Investigational" means that drug combination is being studied.
The FDA (the U.S. Food and Drug Administration) has not approved Utomilumab as a treatment for any disease.
The FDA (the U.S. Food and Drug Administration) has approved Avelumab as a treatment for other diseases.
The FDA (the U.S. Food and Drug Administration) has approved trastuzumab as a treatment option for this disease.
The FDA (the U.S. Food and Drug Administration) has approved vinorelbine as a treatment for other diseases and is commonly used as a treatment option for this disease.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years or older
- •Histologically confirmed breast adenocarcinoma that is unresectable loco-regionally advanced or metastatic
- •HER2-positive (immunohistochemistry score 3+) or ERBB2- amplification (Ratio ERBB2/centromeres ≥ 2.0 or mean gene copy number ≥ 6) on primary tumor or of metastatic or unresectable loco-regional biopsy.
- •Measurable disease per RECIST v1.1 (see Section 11)
- •Patients must have previous treatment with ado-trastuzumab emtansine (Kadcyla, T-DM1) in any setting. Patients must have previously received trastuzumab and pertuzumab in the metastatic setting or within 12 months of neoadjuvant/adjuvant treatment.
- •Patient must have progressed on their most recent line of therapy. Progression must have been demonstrated by radiological or clinical assessment.
- •Left ventricular ejection fraction (LVEF) ≥ 50%
- •Willingness and availability to submit FFPE tissue for central confirmation of HER2 positivity and central assessment of PD-L1 status. This can be from archival tissue from unresectable loco-regional or metastatic disease obtained ≤ 1 year prior to enrollment or new tissue material from a recently obtained surgical or diagnostic biopsy. Tissue obtained for the biopsy must not have been previously irradiated. If a patient does not have any available archival tissue ≤ 1 year old and the treating investigator does not feel that it would be safe to perform a fresh biopsy, the requirement for a fresh biopsy may be waived after discussion with the Principal Investigator.
- •Written informed consent for screening and trial participation procedures including biological material transfer and handling.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Hematopoietic status:
- •Absolute neutrophil count ≥ 1.0 × 109/L,
- •Platelet count ≥ 100 × 109/L,
- •Hemoglobin ≥ 9 g/dL
- •Hepatic status:
- •Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN). In the case of known Gilbert's syndrome, a higher serum total bilirubin (< 2 × ULN) is allowed.
- •AST and ALT ≤ 2.5 × ULN; if the patient has liver metastases, ALT and AST must be ≤ 5 × ULN.
- •Renal status:
- •Creatinine ≤ 1.5 ×ULN or creatinine clearance > 60 ml/min
- •Proteinuria < 1 g/day
- •International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 × ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulant.
- •If female of childbearing potential, must have a negative pregnancy test within 7 days of initiating treatment. Childbearing potential is defined by: those who have not been surgically sterilized and/or have had a menstrual period in the past year.
- •Participants of childbearing potential (as defined above) must be willing to use effective contraception during treatment and up to 7 months after stop of trial treatment. Acceptable methods of contraception are intrauterine devices, bilateral tubal occlusion, vasectomized, or total abstinence. Oral, injectable, or implant hormonal contraceptives are not allowed.
- •Must not be breastfeeding/lactating.
排除标准
- •Prior therapy with any anti-PD-1, anti-PD-L1, L2, anti-4-1BB (CD137), or anti-CTLA4 therapy
- •Known Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
- •Positive for Hepatitis B (HBsAg reactive) or Hepatitis C (HCV RNA [qualitative]).
- •History of interstitial lung disease
- •Active central nervous system metastases, as indicated by clinical symptoms, cerebral edema, and/or progressive growth (patients with history of CNS metastases or spinal cord compression are eligible if they are clinically stable for at least 4 weeks before first dose of investigational product and do not require high-dose steroid treatment).
- •History of clinically significant or uncontrolled cardiac disease, including congestive heart failure (New York Heart Association functional classification ≥3), angina, myocardial infarction or ventricular arrhythmia.
- •Previous severe hypersensitivity reaction to treatment with another monoclonal antibody.
- •Active infection requiring systemic therapy.
- •Chronic systemic therapy with immunosuppressive agents including corticosteroids.
- •Active autoimmune disease or a documented history of autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Patients with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Patients that require intermittent use of bronchodilators or local steroid injections would not be excluded from the trial. Patients with hypothyroidism stable on hormone replacement or Sjögren's syndrome will not be excluded from the trial.
- •Concurrent disease or condition that would make the patient inappropriate for trial participation or any serious medical disorder that would interfere with the patient's safety.
- •No uncontrolled hypertension (≥180/110), unstable diabetes mellitus, dyspnea at rest, or chronic therapy with oxygen.
- •Chemotherapy, radiotherapy, and/or biological cancer therapy within 3 weeks prior to the first trial dose or has not recovered to CTCAE v.4 grade 1 or better from adverse events (except alopecia).
- •Unresolved or unstable, serious adverse events from prior administration of another investigational drug.
- •Live vaccines within 30 days prior to the first dose of trial therapy and during trial treatment.
研究组 & 干预措施
NH: Trastuzumab + Vinorelbine
Experimental
- Trastuzumab is administered intravenously twice per cycle
- Vinorelbine is administered intravenously 3 times per cycle
干预措施: Vinorelbine (Drug)
NH: Trastuzumab + Vinorelbine
Experimental
- Trastuzumab is administered intravenously twice per cycle
- Vinorelbine is administered intravenously 3 times per cycle
干预措施: Trastuzumab (Drug)
NHA: Trastuzumab + Vinorelbine + Avelumab
Experimental
- Trastuzumab is administered intravenously twice per cycle
- Vinorelbine is administered intravenously 3 times per cycle
- Avelumab is administered intravenously twice per cycle
- Antihistamine and with acetaminophen is mandatory 30 to 60 minutes prior to each dose of avelumab
干预措施: Avelumab (Drug)
NHAU: Trastuzumab + Vinorelbine + Avelumab + Utomilumab
Experimental
- Trastuzumab is administered intravenously twice per cycle
- Vinorelbine is administered intravenously 3 times per cycle
- Avelumab is administered intravenously twice per cycle
- Antihistamine and with acetaminophen is mandatory 30 to 60 minutes prior to each dose of avelumab
- Utomilumab is administered intravenously once per cycle
干预措施: Vinorelbine (Drug)
NHAU: Trastuzumab + Vinorelbine + Avelumab + Utomilumab
Experimental
- Trastuzumab is administered intravenously twice per cycle
- Vinorelbine is administered intravenously 3 times per cycle
- Avelumab is administered intravenously twice per cycle
- Antihistamine and with acetaminophen is mandatory 30 to 60 minutes prior to each dose of avelumab
- Utomilumab is administered intravenously once per cycle
干预措施: Trastuzumab (Drug)
NHA: Trastuzumab + Vinorelbine + Avelumab
Experimental
- Trastuzumab is administered intravenously twice per cycle
- Vinorelbine is administered intravenously 3 times per cycle
- Avelumab is administered intravenously twice per cycle
- Antihistamine and with acetaminophen is mandatory 30 to 60 minutes prior to each dose of avelumab
干预措施: Vinorelbine (Drug)
NHA: Trastuzumab + Vinorelbine + Avelumab
Experimental
- Trastuzumab is administered intravenously twice per cycle
- Vinorelbine is administered intravenously 3 times per cycle
- Avelumab is administered intravenously twice per cycle
- Antihistamine and with acetaminophen is mandatory 30 to 60 minutes prior to each dose of avelumab
干预措施: Trastuzumab (Drug)
NHAU: Trastuzumab + Vinorelbine + Avelumab + Utomilumab
Experimental
- Trastuzumab is administered intravenously twice per cycle
- Vinorelbine is administered intravenously 3 times per cycle
- Avelumab is administered intravenously twice per cycle
- Antihistamine and with acetaminophen is mandatory 30 to 60 minutes prior to each dose of avelumab
- Utomilumab is administered intravenously once per cycle
干预措施: Avelumab (Drug)
NHAU: Trastuzumab + Vinorelbine + Avelumab + Utomilumab
Experimental
- Trastuzumab is administered intravenously twice per cycle
- Vinorelbine is administered intravenously 3 times per cycle
- Avelumab is administered intravenously twice per cycle
- Antihistamine and with acetaminophen is mandatory 30 to 60 minutes prior to each dose of avelumab
- Utomilumab is administered intravenously once per cycle
干预措施: Utomilumab (Drug)
结局指标
主要结局
Progression Free Survival
时间窗: 2 years
Progression Free Survival is defined from the time from randomization to the first occurrence of disease progression as determined by the investigator using RECIST 1.1 or death from any cause, whichever occurs first.
次要结局
- Overall Survival(5 years)
- Duration of Response(3 years)
- Objective Response Rate(2 years)
研究者
Adrienne G. Waks
Principal Investigator
Dana-Farber Cancer Institute
研究点 (21)
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