Integration of Whole-Genome Sequencing Profiles and Immune Status in Cancer - a Molecular Profiling Protocol to Broaden the View on Drug Targets and Immune Contexture in Patients With Melanoma and Pancreatic Cancer
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 180
- 试验地点
- 1
- 主要终点
- Number of tumour WGS and immune profiles
研究概览
简要总结
The goal of this investigator-initiated tumour profiling study is to analyse the relation between genomic alterations and the tumour immune contexture in patients with advanced melanoma and pancreatic cancer with resistance to (immuno)therapy, aiming to identify targets and approaches for future (combination) treatment. The main endpoint of this study is the number of patients for whom both tumour WGS and immune profiles could be adequately obtained.
The co-primary endpoint is the frequency of "inflamed" vs "immune excluded/desert" tumours (based on tumour infiltrating immune cells) in patients with i) NRAS/KRAS mutant vs wild-type tumours and ii) High vs low mutational tumour load.
Participants will undergo an extra tumour biopsy procedure and venepuncture once during a tumour biopsy procedure done performed as part of standard treatment.
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
- •Diagnosis of locally advanced or metastatic cutaneous/mucosal melanoma or pancreatic cancer, meeting the following characteristics:
- •a. Melanoma i. Patients with histologically proven locally advanced or metastatic melanoma (stage IV), with intrinsic or acquired resistance to treatment with immune checkpoint inhibition (anti-PD1 antibody +/- ipilimumab) ii. Patients with locoregional or distant recurrence either during, or within 3 months after completion or discontinuation of (neo)adjuvant anti-PD1-based immunotherapy for stage III melanoma.
- •b. Pancreatic cancer i. Patients with histologically proven metastatic pancreatic cancer with progression under or after standard first-line chemotherapy with FOLFIRINOX.
- •Patients must be willing and able to provide written informed consent and be willing and able to comply with the study protocol.
- •Patients must be ≥18 years of age.
- •Metastatic or locoregional lesion of which a tumour needle biopsy can be safely obtained according to routine clinical practice.
排除标准
- •- Patients with metastatic or locally advanced lesions which are not considered to be technically and/or safely biopsied.
研究组 & 干预措施
Single arm tumour profiling study
Patients undergo tumour biopsy and blood draw once
干预措施: Biopsy (Procedure)
结局指标
主要结局
Number of tumour WGS and immune profiles
时间窗: through study completion, an average of 1 year
number of patients for whom both tumour WGS and immune profiles could be adequately obtained
"inflamed" vs "immune excluded/desert" tumours
时间窗: through study completion, an average of 1 year
The co-primary endpoint is the frequency of "inflamed" vs "immune excluded/desert" tumours (based on tumour infiltrating immune cells) in patients with i) NRAS/KRAS mutant vs wild-type tumours and ii) High vs low mutational tumour load
次要结局
- The percentage of patients with evaluable tumour DNA, RNA and (tissue and peripheral) immune profiles(Through study completion, an average of 2 year)
- Differences between the post-immunotherapy and post-chemotherapy mutational/RNA-profiles with pre-treatment profiles (e.g. copy numbers, mutational load, genetic aberrations) of a similar cohort of patients who participated(After study completion, an average of 2 year)
- The relation between tumour and peripheral immune profiles and changes over time in patients with intrinsic vs acquired resistance to immune checkpoint inhibition(After study completion, an average of 2 year)
- The percentage of patients with melanoma with evaluable (phospho)proteomic profiles(After study completion, an average of 2 year)
- The frequency of (potentially) actionable genomic alterations(Through study completion, an average of 2 year)
研究者
Mariette Labots
Principal Investigator
Amsterdam UMC, location VUmc