Rational Approach To Immuno-Oncology Microarray Prediction of Response to Nivolumab, Ipilimumab, or Combined Therapy in Subjects With Previously Untreated, Locally Advanced or Metastatic Melanoma
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 35
- 试验地点
- 2
- 主要终点
- Correlation of the MMDx from pretreatment biopsy with overall response rate (ORR).
研究概览
简要总结
This trial will utilize a Molecular MicroscopeTM diagnostic system (MMDxTM) that combines the molecular and histopathological features of biopsies, plus clinical and laboratory parameters, to create the first Integrated Diagnostic System. This MMDxTM will be utilized to phenotype cutaneous melanoma biopsy samples to detect an immune responsive mRNA signature.
详细描述
The trial treatment will consist of a pretreatment 18 gauge core biopsy of locally advanced or metastatic cutaneous or subcutaneous lesions. The biopsies will be stabilized on site in RNAlater and shipped to ATAGC by courier at ambient temperature. RNA will be extracted using Trizol-chloroform method and purified using RNAEasy micro kit (Qiagen). RNA samples passing the quality control test (Agilent Bioanalyzer) will be labeled, hybridized to PrimeView Affymetrix microarrays and scanned according to the manufacturer's protocol. Resulting ".CEL" files will be used for the analysis of the global gene expression.
Pathogenesis Based Transcript (PBT) sets that represent molecular signatures of inflammation will be assessed in core biopsies from melanoma patients. Each PBT set gets a "score" - a summarized expression of all members of a set. PBT scores allow an estimate of pre and post-treatment immunological activity in each tumor e.g. TCMR activity or macrophage burden. PBT scores will be correlated with clinical outcome to determine the utility of this technology as a prognostic and predictive biomarker. Finally a molecular classifier predicting the response to therapy will be built.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 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
- •Men and women, > 18 years of age
- •Histologically confirmed locally advanced or metastatic melanoma with cutaneous or subcutaneous lesions
- •Immunotherapy treatment naïve subjects (ie, no prior systemic anticancer therapy for unresectable or metastatic melanoma)
- •Scheduled to receive ipilimumab, nivolumab, or combination treatment
- •Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2
- •Not pregnant or lactating. Women who are of child-bearing potential must agree to use an effective means of birth control (i.e., latex condom, diaphragm, cervical cap, etc) to avoid pregnancy.
- •Informed consent for microarray analysis of locally advanced lesion or skin metastasis retrieved by standard of care biopsy
排除标准
- •Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co- stimulation or immune checkpoint pathways
- •Subjects with active, known, or suspected autoimmune disease
- •If considered high-risk and tested for hepatitis: Any positive test result for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
- •Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
- •Any significant medical condition, laboratory abnormality, or psychiatric illness, that would prevent the subject from participating in the study, places the subject at unacceptable risk if he/she were to participate in the study, or any condition that confounds the ability to interpret data from the study
结局指标
主要结局
Correlation of the MMDx from pretreatment biopsy with overall response rate (ORR).
时间窗: 24 months
次要结局
- Overall Survival (OS)(24 months)
- Progression Free Survival (PFS)(24 months)