An interventional study of blood sampling in Non Small Cell Lung Cancer, sponsored by Hellenic Oncology Research Group. Status unknown at 6 sites in Greece. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-12-11.
Sponsored by Hellenic Oncology Research Group · Not applicable, Interventional, and Other
The purpose of his study is to investigate the intra tumor heterogeneity of the primary tumor and the involved lymph nodes from patients with resectable NSCLC, to detect primary tumor genetic alternations using "liquid biopsy" during the patients' clinical follow up and to correlate the "liquid biopsy" information with the disease recurrence.
Lung cancer is the most common cancer in the world. In operable early stage patients NSCLS can be curable, but even after complete primary tumor resection, about 45% of early stage patients develop local or distant recurrence within 8-18 months. Recent studies have established that targeted therapies may fail to cure the disease because of tumor heterogeneity. The presence of genetic heterogeneity in different portions of a tumor have demonstrated its importance in tumor biology suggesting that pre-existing genetically different sub clones may be selected by therapy or differentially involved in the metastatic process, leading to treatment failure.
The relationship of tumor heterogeneity with the poor clinical outcome suggests that its assessment could provide interesting and useful clinical information, especially, in terms of prognosis and treatment selection. It is now, well established that during the evolution of tumor new cellular clones could be emerged which differ genetically from the molecular signature of tumor cells evaluated at the time of initial diagnosis. This molecular evolution may further contribute to the tumor heterogeneity during the disease progression. The evaluation of the real-time molecular tumor heterogeneity requires repeated re-biopsies during the different clinical phases of NSCLC which, however, are invasive and not, always, feasible. This problem can be by-passed by the use of tumor-originating elements in the plasma and among these cellular products the isolation and analysis of cell tumor DNA (ctDNA) and the characterization of Circulating Tumor Cells (CTCs) represent important tools for identification and monitoring of molecular tumor alterations in cancer patients, representing what the investigators call "liquid biopsy". ctDNA is originated from cellular necrosis due to increased tumoral cellular turnover and cellular ischemia as well as from apoptosis of tumor cells or lysis of Circulating Tumor Cells (CTCs). On the other hand, the CTCs, which designate the cells circulating in the blood, can be detected in several tumor types, irrespectively of the clinical phase, and their detection has been correlated with disease progression and treatment resistance. Therefore, the concomitant analysis of both ctDNA and CTCs could permit to better evaluate the genetic heterogeneity of the tumor since they continuously released from tumor cells throughout the clinical course of the disease and is considered to be proportional to tumor burden and tumor progression at each time-point.
This is a multicenter, single arm, non-randomized translational research study. Patients with operable NSCLC will be enrolled in the study. Patients' peripheral blood will be obtained before the surgical excision of the primary tumor as well as 1-month post-op and every 3-6 months thereafter until disease progression and upon disease relapse for the evaluation of ctDNA and CTCs. Different sites of the primary tumor as well as the regional involved lymph nodes and, in selected patients, biopsies from metastatic sites will be genotyped by NGS as well.
6,488 studies on the registry are indexed under Carcinoma, Non-Small-Cell Lung; 1,632 are open to participants now.
This study's planned enrollment of 50 is below the median of 62 across 5,213 interventional studies indexed under Carcinoma, Non-Small-Cell Lung.
Browse Carcinoma, Non-Small-Cell Lung studies →Hellenic Oncology Research Group is the lead sponsor of 57 studies on the registry; none are open to participants now.
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Exclusion Criteria:
For Operable (stages I-IIIA) NSCLC Patients, blood sampling and tissue samples of the primary tumor as well as the regional involved lymph nodes and, in selected patients, from biopsies from metastasis
Other: blood sampling
Patients' peripheral blood will be obtained before the surgical excision of the primary tumor as well as 1-month post-op and every 3-6 months thereafter until disease progression and upon disease relapse for the evaluation of ctDNA and CTCs. Different sites of the primary tumor as well as the regional involved lymph nodes and, in selected patients, biopsies from metastatic sites will be genotyped by NGS as well.
Also known as: primary tumor sampling after surgery, biopsy from metastatic sites in selected patetients
To evaluate whether the individual patient's molecular landscape of ctDNA and CTCs could be reliable biomarkers for the early prediction of disease relapse.
The initial tumor of all patients will be submitted to Next Generation Sequencing (NGS) in order to detect mutations and copy-number variations to the following set of genes: AKT1, KRAS, NRAS, BRAF, DDR2, EGFR, FGFR1, ERBB2 (HER2), MEK1, MET, PIK3CA, PTEN, TP53, MDM2, SOX2 and P63. Detected mutations will be monitored longitudinally in ctDNA from patient's blood samples by ddPCR, for a 2-year period or until PD. For each subject, molecular analysis results will be correlated with its clinical outcome in terms of time to disease progression (PFS). CTCs will be isolated based on the cell's size. CTCs isolated by ISET will be phenotypically characterized to define their proliferative, apoptotic, EMT status as well as their immune profile using antibodies and immunofluorescent staining. CTCs isolated by PARSORTIX will be analyzed for the detection of specific genetic changes present in the primary tumor (see NGS analysis of primary tumor) using either qRT-PCR or FISH analysis.
Time frame: Up to 2 years
To investigate the genetic heterogeneity in resectable NSCLC
The initial tumor of all patients will be submitted to Next Generation Sequencing (NGS) in order to detect mutations and copy-number variations to the following set of genes: AKT1, KRAS, NRAS, BRAF, DDR2, EGFR, FGFR1, ERBB2 (HER2), MEK1, MET, PIK3CA, PTEN, TP53, MDM2, SOX2 and P63.
Time frame: Up to 2 years
To monitor using "liquid biopsy" the tumor clonal evolution during the post operation period and define a correlation between the genotype of the primary tumor and the emergence of molecularly different clones
The initial tumor of all patients will be submitted to Next Generation Sequencing (NGS) in order to detect mutations and copy-number variations to the following set of genes: AKT1, KRAS, NRAS, BRAF, DDR2, EGFR, FGFR1, ERBB2 (HER2), MEK1, MET, PIK3CA, PTEN, TP53, MDM2, SOX2 and P63. Detected mutations will be monitored longitudinally in ctDNA from patient's blood samples by droplet digital Polymerase Chain Reaction (ddPCR), for a 2-year period or until PD.
Time frame: Up to 2 years
To investigate the potential of longitudinal "liquid biopsy" to predict the genetic profile of metastasis
The initial tumor of all patients will be submitted to Next Generation Sequencing (NGS) in order to detect mutations and copy-number variations to the following set of genes: AKT1, KRAS, NRAS, BRAF, DDR2, EGFR, FGFR1, ERBB2 (HER2), MEK1, MET, PIK3CA, PTEN, TP53, MDM2, SOX2 and P63. Detected mutations will be monitored longitudinally in ctDNA from patient's blood samples by droplet digital Polymerase Chain Reaction (ddPCR), for a 2-year period or until PD. Moreover, in patients where metastasis re-biopsy is feasible the metastasis tumor will be submitted to Next Generation Sequencing (NGS) in order to detect mutations and copy-number variations to the set of genes mentioned above. Correlation between the molecular analysis of the primary tumor, the ctDNA and the metastasis tumor will reveal whether longitudinal liquid biopsy can predict the metastasis genetic profile.
Time frame: Up to 2 years
Plan to share: No
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Carcinoma, Non-Small-Cell Lung→
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