A Pilot Study of ctDNA-Guided Immune Checkpoint Inhibitor Duration in Patients With Advanced Melanoma.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Primary Outcome
研究概览
简要总结
This is a phase II pilot study evaluating the use of circulating tumor DNA (ctDNA) to guide the optimal duration of standard of care immune checkpoint inhibitor (ICI) therapy in patients with unresectable and/or metastatic melanoma who have radiographic evidence of disease control and/or response to treatment.
详细描述
This is a study of patients with advanced melanoma who are potentially eligible to stop or shorten their duration of ICI. Patients with radiographic disease control and/or response with undetectable ctDNA levels will stop ICI therapy after 1 year. Patients who have responded to ICI but have experienced immune-related adverse events (irAE) requiring treatment interruption and immunosuppression are also eligible and will stop ICI therapy if ctDNA is undetectable. All patients with undetectable ctDNA who candidates are to stop treatment will undergo monitoring with standard of care imaging and ctDNA assessments every three months to assess for the primary outcome of the 12-month sustained ctDNA negativity rate. Undetectable ctDNA for the purposes of the treatment duration decision time point is defined as two consecutive negative ctDNA tests performed at least 4 weeks apart.
If ctDNA is detectable at the treatment duration decision time point, treatment will be continued as per an investigator's choice regimen. In patients whose ctDNA converts from undetectable to detectable during the monitoring period, the investigator may choose to restart ICI based upon imaging findings and/or other relevant clinical factors.
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
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age > 18 with any subtype of unresectable stage III or stage IV melanoma treated with anti-PD-1-based ICI which includes both anti-PD-1 monotherapy and dual checkpoint inhibitor regimens such as ipilimumab plus nivolumab and nivolumab plus relatlimab.
- •Disease control after at least 6-12 months of anti-PD-1-based ICI defined as a radiographic RECIST CR, PR, or SD and planned for at least 1 year of treatment
- •Development of an irAE(s) on an anti-PD-1-based regimen requiring treatment interruption and immunosuppression where the investigator is considering treatment discontinuation. Patients must have a radiographic RECIST PR or CR at the treatment duration decision time point.
- •Any line of therapy, with the exception of adjuvant therapy.
- •Ability to understand and the willingness to sign a written informed consent document.
- •Patients with brain metastasis may be included only if there was also presence of extracranial disease.
- •ECOG performance status 0-2.
排除标准
- •Participants who are receiving investigational therapies.
- •Inadequate tumor quantity or quality to conduct initial Signatera ctDNA testing.
- •Intracranial-only metastatic melanoma.
- •Patients with best response of progressive disease at time of screening.
- •Patients who have had their melanoma completely surgically resected such that response to immunotherapy is no longer evaluable.
- •Patients who are unwilling to continue or stop ICI therapy using ctDNA guidance in combination with imaging response.
- •History of a life-threatening or severe irAE that would make ICI rechallenge unsafe. These cases will be discussed with the Principal Investigator.
- •Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
研究组 & 干预措施
ctDNA Feasibility
feasibility of utilizing ctDNA levels to inform immunotherapy treatment duration decisions in patients with advanced melanoma, in conjunction with standard imaging assessments to judge response.
干预措施: A Pilot Study of ctDNA-guided immune checkpoint inhibitor duration in patients with advanced melanoma (Other)
结局指标
主要结局
Primary Outcome
时间窗: 12-month sustained ctDNA negativity rate after ICI discontinuation
To determine whether ctDNA can safely and feasibly guide ICI treatment duration decisions in patients with advanced melanoma by measuring the proportion of patients who demonstrate persistently undetectable ctDNA in the 12 months following treatment discontinuation
次要结局
- Secondary Outcome 1(1-year progression-free survival (PFS) among patients with undetectable ctDNA who discontinue ICI)
- Secondary Outcome 2(1-year overall survival (OS) among patients with undetectable ctDNA who discontinue ICI)
- Outcome measure 3(1-year treatment-free survival (TFS) among patients with undetectable ctDNA who discontinue ICI)
研究者
Sarah Weiss
Associate Professor of Medicine, Division of Medical Oncology
Rutgers, The State University of New Jersey