Molecular Profiling and Dynamic Changes of ctDNA in Unresectable Locally Advanced NSCLC

Lung Cancer Clinical Trial

Official title:

Molecular Profiling and Dynamic Changes of Circulating Tumor DNA in Unresectable Locally Advanced Non-small Cell Lung Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05641870
• Other study ID #: 2022/10344/I
• Status: Recruiting
• Start date: February 1, 2021
• Est. completion date: December 2023

Study information

• Verified date: December 2022
• Source: Parc de Salut Mar
• Contact: Edurne Arriola
• Phone: 932483137
• Email: earriola[@]psmar.cat
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms
• Stage III Lung Cancer
• Unresectable Lung Carcinoma

Intervention

Procedure:
• Sample 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 Test:
• Characterization 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.

Drug:
• Chemoradiation 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 Test:
• Genomic 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.

Locations

Country	Name	City	State
Spain	Parc de Salut Mar - Hospital del Mar	Barcelona

Sponsors (2)

Lead Sponsor	Collaborator
Parc de Salut Mar	GUARDANT HEALTH

Country where clinical trial is conducted

Spain, 

References & Publications (15)

Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Kurata T, Chiappori A, Lee KH, de Wit M, Cho BC, Bourhaba M, Quantin X, Tokito T, Mekhail T, Planchard D, Kim YC, Karapetis CS, Hiret S, Ostoros G, Kubota K, Gray JE, Paz-Ares L, de Castro Carpeno J, Faivre-Finn C, Reck M, Vansteenkiste J, Spigel DR, Wadsworth C, Melillo G, Taboada M, Dennis PA, Ozguroglu M; PACIFIC Investigators. Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. N Engl J Med. 2018 Dec 13;379(24):2342-2350. doi: 10.1056/NEJMoa1809697. Epub 2018 Sep 25. — View Citation

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* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Quantitative variation of aberrant methylated ctDNA concentrations before chemoradiotherapy, after chemoradiotherapy, and every 3 months during 1 year of follow-up.		16 months
Primary	Correlation between patients' recurrence or progression, and quantitative detection of circulating tumour DNA (ctDNA) concentration.		2 years
Primary	Concordance of ctDNA genomic alterations detected in peripheral blood samples, with those in matched tumour samples.		At diagnosis
Primary	Correlation between survival outcomes (progression free survival, overall survival) and quantitative detection of ctDNA genomic alterations or methylation status.		2 years