|- candidate number||27070|
|- NTR Number||NTR6390|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||10-apr-2017|
|- Secondary IDs||METC 2017/217|
|- Public Title||Translational research for immune modulating and targeted therapy in advanced or metastatic non-small cell lung cancer, an exploratory NVALT study|
|- Scientific Title||Translational research for immune modulating and targeted therapy in advanced or metastatic non-small cell lung cancer, an exploratory NVALT study|
|- ACRONYM||Translational research for immune modulating and targeted therapy in advanced or metastatic NSCLC|
|- hypothesis||1. The predictive biomarkers for tumor response to immuno modulating therapy will be a combination of adaptive and innate immune status per patient that will be estimated with a tumor biopsy before, 6 weeks after start treatment (optional) and at progression or recurrence of disease and blood sampling at baseline, in week 2 or 3, 6, 12 and at progression or recurrence of disease. This status can be defined as the different immune cell fractions estimated by CIBERSORT and the LM22 leukocyte signature matrix estimated from RNA sequencing data. Another approach is looking for activating T8+ cells and inhibitory Treg, macrophages and myeloid suppressor cells by immune fluorescence tests in the same biopsy by multispectral imaging. In combination with clinical data the meaning of the different fractions can be assessed in a prospective way. |
2. Resistance to targeted therapy that develop early in the course of disease will be limited to gate keeper mutations and a complex delayed resistance due to a multitude of mechanisms.These resistance mechanisms can be discerned by a biopsy from the growing tumor. DNA and RNA seq data will used to illuminate patterns of resistance.
|- Healt Condition(s) or Problem(s) studied||Non small cell lung cancer (NSCLC)|
|- Inclusion criteria||1. Eligible for immunotherapy or targeted treatment.|
2. Written informed consent for registry of patient data and extra blood and tumor biopsy.
3. Age 18 years and older.
|- Exclusion criteria||1. Without written informed consent patient will be adopted anonymously in the registry and will not take part of the study. |
2. Patients with written informed consent for registry of patient data but no consent for extra blood and tumor biopsy will be excluded from the study.
|- mec approval received||no|
|- multicenter trial||no|
|- Type||Single arm|
|- planned startdate ||1-mei-2017|
|- planned closingdate||1-mei-2021|
|- Target number of participants||300|
|- Interventions||Blood drops and optionally a tumor biopsy|
|- Primary outcome||• Relation between adaptive and innate immune status and tumor response rate, PFS and OS.|
• Relation between gate keeper mutations and complex mutations with tumor response rate, PFS and OS on treatments used by treating physician.
• Correlation of the baseline ctDNA level with tumor response rate, PFS and OS
• Correlation of the change in ctDNA level after six weeks of treatment to ORR, PFS and OS.
• Validated tumor educated platelet algorithm that is associated with increased ORR, PFS and OS.
• Validated tumor educated platelet algorithm that is associated with therapy resistance.
• Correlation of STM-panel based response assessment with radiological response assessment as performed by CT-thorax.
• Correlation of PBMC FACS parameters of lymphoid and myeloid subsets in peripheral blood to tumor response rate, PFS and OS.
• Correlation of rare mutation profile, as assessed by NGS on tumor tissue, to tumor response rate, PFS and OS.
• Correlation of tumor tissue IHC parameters to tumor response rate, PFS and OS.
• Correlation of RNAseq on fresh frozen tumor tissue to tumor response rate, PFS and OS.
• Correlation of CT based parameters to tissue parameters and tumor response rate, PFS and OS.
• Correlation of differences between CT based (textural) parameters and tissue parameters and tumor response rate.
|- Secondary outcome||-|
|- Timepoints||Blood sampling: 1 whole blood and 2 EDTA at baseline, week 2 or 3, week 6, week 12 and at progression or recurrence of disease. |
Tumor biopsie will be taken at baseline, week 6 and at progression or recurrence of disease.
|- Trial web site|
|- CONTACT FOR PUBLIC QUERIES||Prof. Dr. H.J.M. Groen|
|- CONTACT for SCIENTIFIC QUERIES||Prof. Dr. H.J.M. Groen|
|- Sponsor/Initiator ||NVALT|
(Source(s) of Monetary or Material Support)
|- Brief summary||In this study we will explore frozen and paraffin embedded (FFPE) tumor tissue and blood samples from patients that are eligible for immune- and targeted therapy and those who become resistant to immune- and targeted therapy after an initial response. Frozen tumor biopsies will be used for RNA seq and FFPE tissue will be stained with multiple fluorescent targets to identify stimulating and inhibiting immune cells in the tumor. Moreover, blood will be collected to explore the role of circulating blood markers.|
|- Main changes (audit trail)|
|- RECORD||10-apr-2017 - 21-jun-2017|