Lung Cancer, Stage III Lung Cancer, Unresectable Lung Carcinoma
Conditions
Keywords
Liquid biopsy, ctDNA, Chemoradiotherapy
Brief summary
Multi-center observational clinical study to evaluate the application value of ctDNA monitoring in efficacy assessment and relapse prediction in patients diagnosed with unresectable, locally advanced NSCLC receiving CRT with or without durvalumab maintenance treatment.
Detailed description
Newly diagnosed, histologically confirmed, unresectable stage III NSCLC patients, amenable to receive standard of care chemoradiotherapy with or without durvalumab maintenance, will be enrolled in this study. Whole blood collection will be conducted during the treatment for ctDNA detection in specific time-points of interest. Next-generation sequencing using commercially available panels, and analysis of ctDNA aberrant methylation will be performed. Results will be correlated to patients' recurrence times and survival outcomes.
Interventions
PROCEDURESample collection
Tumor samples will be collected as standard diagnostic procedure at diagnosis. Plasma samples from whole blood extractions will also be collected at diagnosis, after chemoradiotherapy, and every 3 months from there until completing one year of follow-up.
DIAGNOSTIC_TESTCharacterization of the tumoral tissue genomic alterations
Genomic alterations of tumor tissue samples will be analyzed locally by next-generation sequencing when material is adequate, as standard diagnostic procedure.
DRUGChemoradiation treatment regimen and maintenance (if amenable)
Patients will be treated with standard chemotherapy (following the clinical practice at each institution). Radiotherapy will be delivered concurrently when feasible with a total dose of 60-66 Gy. In selected cases, due to frailty of the patient or impaired pulmonary function, radiotherapy will be delivered sequentially. In tumors with positive PD-L1 expression, a year of durvalumab 10 mg/m2 every 2 weeks will be administered if there are no contraindications.
DIAGNOSTIC_TESTGenomic and methylation analysis in liquid biopsy
Blood samples for ctDNA genomic and methylation analysis (4 mL of plasma for each sample) will be sent to the Guardant Health Laboratories in the US and analyzed after Contractual Agreement signature, using the Guardant Reveal test. This liquid biopsy test uses ctDNA to detect presence of MRD and monitor for recurrence after definitive surgical/systemic therapy for patients with cancer. It has been validated in early-stage colorectal cancer and integrates assessment of somatic alterations with an epigenomic cancer signature to identify the presence of methylation signatures associated with cancer versus normal DNA.
Sponsors
Guardant Health, Inc.
Parc de Salut Mar
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with newly diagnosed, histologically confirmed, unresectable locally advanced NSCLC. * ≥18 years of age. * Ability to understand the written informed consent and willingness to sign it.
Exclusion criteria
* Patients who are unwilling to follow-up evaluation of response to therapy. * Any condition that, in the opinion of the investigator, would interfere with study results.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Quantitative variation of aberrant methylated ctDNA concentrations before chemoradiotherapy, after chemoradiotherapy, and every 3 months during 1 year of follow-up. | 16 months |
| Correlation between patients' recurrence or progression, and quantitative detection of circulating tumour DNA (ctDNA) concentration. | 2 years |
| Concordance of ctDNA genomic alterations detected in peripheral blood samples, with those in matched tumour samples. | At diagnosis |
| Correlation between survival outcomes (progression free survival, overall survival) and quantitative detection of ctDNA genomic alterations or methylation status. | 2 years |
Countries
Spain
Contacts
Primary ContactEdurne Arriola
Backup ContactPedro Rocha
Outcome results
None listed