A Pilot Study of Blood-Based Biomarkers for Response to Immune Checkpoint Inhibitors
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Percentage of patients with tumor fraction change
研究概览
简要总结
A pilot study evaluating baseline and on-treatment changes in tumor fraction (TFx) in peripheral blood in patients with NSCLC and RCC being treated with checkpoint inhibitor therapy as part of standard of care. The primary objective of the study is to determine whether baseline TFx can be reliably predicted in patients with NSCLC and RCC and if changes can be detected during treatment that may correlate with response. Exploratory analyses will be completed to assess the potential roles of cachexia-associated inflammation, tumor-associated increases in glucocorticoid secretion, and ketosis/ketogenesis in both elevated mAb clearance and in response to ICI therapy. Measurements will include circulating IL-6 and other cytokine levels, glucocorticoid levels, ketone levels and stool analysis for assessment of gut microbiome.
详细描述
Primary objective:
The primary objective of this protocol is to establish whether TFx can be reliably measured in patients with NSCLC and RCC undergoing treatment with ICI
Secondary objectives:
- To incorporate and evaluate relationships among other known risk factors for cachexia relative to ICI therapy pharmacokinetics and clinical outcomes (to include baseline and longitudinal measures of body weight, body composition determinations via L3 CT scans, and albumin for cachexia, and baseline ICI mAb clearance and changes in clearance over time for PK).
- To determine whether detected changes in TFx can be appreciated during treatment and whether these changes are associated with clinical benefit by RECIST v1.1, progression free survival (PFS) and overall survival (OS).
Exploratory Objectives:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- •Males and females, age ≥ 18 years
- •Cohort A will include patients with confirmed diagnosis of all non-small cell lung cancer (NSCLC) histologies including adenocarcinoma, squamous cell, adenosquamous, sarcomatoid/pleomorphic, and poorly differentiated/NOS, as well as patients diagnosed with malignant pleural mesothelioma. Cohort B will include patients with confirmed diagnosis of RCC (clear cell or any non-clear cell histology) receiving first treatment with immunotherapy alone or in combination therapy for metastatic disease or as adjuvant or neoadjuvant therapy.
- •Patients planned for standard of care treatment with immune checkpoint inhibitors (ICIs, see appendix 3 for list) either as monotherapy or in combination therapy.
- •Scheduled for imaging every 6 to 12 weeks for stage IV NSCLC and RCC as is standard of care per NCCN guidelines.
- •Able to read, understand, and provide written informed consent.
- •g. Willing to provide blood specimen and stool samples for research studies as outlined in the calendar h. ECOG performance status 0-2 i. Life expectancy ≥ 3 months
排除标准
- •Individuals <18 years of age
- •Patients who have received previous immune checkpoint inhibitor therapy.
- •Unable or unwilling to provide consent.
- •Other malignancy requiring active ongoing treatment with systemic therapy (excluding hormonal therapy).
- •Women who are known to be pregnant are excluded. However no additional pregnancy testing out of what would be recommended prior to initiating anti-cancer therapy will be performed solely for this study.
- •Patients currently participating in an interventional or therapeutic clinical trial involving the use of active anti-cancer therapy.
结局指标
主要结局
Percentage of patients with tumor fraction change
时间窗: From enrollment up to 12 months
The primary outcome is the percentage of patients having \>5% change (better or worse) in tumor fraction during the first two cycles. With 90 patients having detectable tumor fraction, the % of patients having \>5% change in tumor fraction can be estimated with a 95% confidence interval of ±10%. Assuming the response rate of 30%, 27 responders will provide at least 80% power to detect an effect size of 0.5 standard deviations reduction of tumor fraction from baseline to treatment by cycle 3 at significance level of 0.05, based on a one-sided paired t-test. If the response rate is higher, a smaller reduction can be detected.
次要结局
未报告次要终点
研究者
Dwight Owen
Principal Investigator
Ohio State University Comprehensive Cancer Center