Phase I/II Randomized Study of Combination Immunotherapy With or Without Polysaccharide Krestin (PSK®) Concurrently With a HER2 ICD Peptide-Based Vaccine in Patients With Stage IV Breast Cancer Receiving HER2-Targeted Monoclonal Antibody Therapy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Number of Patients With Grade 3 or Higher Toxicity Per Study Arm.
研究概览
简要总结
This randomized phase I/II trial studies the side effects of vaccine therapy with or without polysaccharide-K and to see how well it works in treating patients with stage IV human epidermal growth factor receptor 2 (HER2) positive breast cancer who are receiving HER2-targeted monoclonal antibody therapy. Vaccines made from HER2 intracellular domain (ICD) peptide may help the body build an effective immune response to kill tumor cells that express HER2. Polysaccharide-K may stimulate the immune system in different ways and stop tumor cells from growing. It is not yet known whether vaccine therapy works better when given with or without polysaccharide-K in treating breast cancer.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the safety of polysaccharide-K (PSK) when given with HER2-directed immunotherapy.
SECONDARY OBJECTIVES:
I. To evaluate the effect of PSK on natural killer (NK) cell functional activity when given with HER2-directed immunotherapy.
TERTIARY OBJECTIVES:
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
- Double (Participant, Investigator)
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
- •Patients with stage IV HER2+ breast cancer treated to:
- •No evidence of disease (NED), or
- •Stable bone only disease after definitive therapy
- •HER2 overexpression by immunohistochemistry (IHC) of 2+ or 3+ in the primary tumor or metastasis; or documented gene amplification by fluorescent in situ hybridization (FISH) analysis; IHC =< 2+ must have HER2 gene amplification documented by FISH
- •Patients must continue HER2-targeted monoclonal antibody therapy dosing per standard of care through the entire study period (one year)
- •HER2-targeted monoclonal antibody therapy is defined as either trastuzumab monotherapy, or trastuzumab and pertuzumab combination therapy administered per standard of care
- •Patients must be at least 21 days post cytotoxic chemotherapy prior to enrollment
- •Patients must be at least 28 days post immunosuppressants prior to enrollment
- •Patients must be at least 28 days from use of any mushroom supplements (examples: turkey tail, reishi, maitake, shiitake) and agree to withhold them for the entire study period (one year)
- •Patients on bisphosphonates and/or endocrine therapy are eligible
- •Patients who are having sex that could lead to pregnancy must agree to contraceptive use during the entire study period
- •Patients must have Zubrod performance status score of =< 2
- •Patients must have recovered from major infections and/or surgical procedures, and in the opinion of the investigator, not have significant active concurrent medical illnesses precluding study treatment
- •White blood cell (WBC) >= 3000/mm^3
- •Hemoglobin (Hgb) >= 10 g/dl
- •Serum creatinine =< 2.0 mg/dl or creatinine clearance > 60 ml/min
- •Total bilirubin =< 1.5 mg/dl
- •Serum glutamic oxaloacetic transaminase (SGOT) =< 2.5 times the upper limit of normal
- •Patients must have adequate cardiac function as demonstrated by normal left ventricular ejection fraction (LVEF) >= the lower limit of normal for the facility on multi gated acquisition (MUGA) scan or echocardiogram (ECHO) within 3 months of enrollment
排除标准
- •Patients with any of the following cardiac conditions:
- •Restrictive cardiomyopathy
- •Unstable angina within 6 months prior to enrollment
- •New York Heart Association functional class III-IV heart failure
- •Symptomatic pericardial effusion
- •Patients with any contraindication to receiving rhu granulocyte macrophage colony stimulating factor (rhuGM-CSF) based products
- •Patients with any clinically significant autoimmune disease requiring active treatment
- •Patients receiving any concurrent immunosuppressants
- •Patients who are pregnant or breast-feeding
- •Patients who are simultaneously enrolled in other treatment studies
- •Patients who have received a previous HER2 breast cancer vaccine
- •Known hypersensitivity reaction to mushroom products
研究组 & 干预措施
Arm I (placebo)
Patients receive HER2 ICD peptide-based vaccine ID once monthly for 3 months, trastuzumab (or trastuzumab and pertuzumab) per standard of care, and placebo PO BID for 4 months.
干预措施: HER-2/neu Intracellular Domain Protein (Biological)
Arm I (placebo)
Patients receive HER2 ICD peptide-based vaccine ID once monthly for 3 months, trastuzumab (or trastuzumab and pertuzumab) per standard of care, and placebo PO BID for 4 months.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (placebo)
Patients receive HER2 ICD peptide-based vaccine ID once monthly for 3 months, trastuzumab (or trastuzumab and pertuzumab) per standard of care, and placebo PO BID for 4 months.
干预措施: Placebo (Other)
Arm II (polysaccharide-K)
Patients receive HER2 ICD peptide-based vaccine ID and trastuzumab (or trastuzumab and pertuzumab) as in Arm I and polysaccharide-K PO BID for 4 months.
干预措施: HER-2/neu Intracellular Domain Protein (Biological)
Arm II (polysaccharide-K)
Patients receive HER2 ICD peptide-based vaccine ID and trastuzumab (or trastuzumab and pertuzumab) as in Arm I and polysaccharide-K PO BID for 4 months.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (polysaccharide-K)
Patients receive HER2 ICD peptide-based vaccine ID and trastuzumab (or trastuzumab and pertuzumab) as in Arm I and polysaccharide-K PO BID for 4 months.
干预措施: Polysaccharide-K (Biological)
Arm II (polysaccharide-K)
Patients receive HER2 ICD peptide-based vaccine ID and trastuzumab (or trastuzumab and pertuzumab) as in Arm I and polysaccharide-K PO BID for 4 months.
干预措施: Pertuzumab (Biological)
Arm I (placebo)
Patients receive HER2 ICD peptide-based vaccine ID once monthly for 3 months, trastuzumab (or trastuzumab and pertuzumab) per standard of care, and placebo PO BID for 4 months.
干预措施: Pertuzumab (Biological)
Arm II (polysaccharide-K)
Patients receive HER2 ICD peptide-based vaccine ID and trastuzumab (or trastuzumab and pertuzumab) as in Arm I and polysaccharide-K PO BID for 4 months.
干预措施: Trastuzumab (Biological)
Arm I (placebo)
Patients receive HER2 ICD peptide-based vaccine ID once monthly for 3 months, trastuzumab (or trastuzumab and pertuzumab) per standard of care, and placebo PO BID for 4 months.
干预措施: Trastuzumab (Biological)
结局指标
主要结局
Number of Patients With Grade 3 or Higher Toxicity Per Study Arm.
时间窗: Up to 4 months
Evaluated using physical examinations and clinical labs by type and grade of toxicities noted during treatment, There were graded per Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events 4.0.
次要结局
- Induction of Interferon (IFN)-Gamma Production and Cluster of Differentiation (CD)107a Expression in NK Cells, Via Flow Cytometry(Up to 16 weeks)
研究者
William Rayford Gwin III, MD
Assistant Professor
University of Washington