Clinical Value of MRD Monitoring for Adjuvant Therapy in Postoperative NSCLC

Carcinoma, Non-Small-Cell Lung Clinical Trial

Official title:

Utility of ctDNA In Predicting Whether Giving Adjuvant Chemotherapy In Patients With Stage IB-IIA Resected Non-small Cell Lung Cancer: A Prospective Cohort Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05167604
• Other study ID #: 777436
• Status: Recruiting
• Start date: September 30, 2021
• Est. completion date: December 2024

Study information

• Verified date: December 2021
• Source: Tang-Du Hospital
• Contact: Yunfeng Ni
• Phone: +86 13772088014
• Email: 264246623[@]qq.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

This clinical trial aims to explore the minimal residual disease (MRD) status of early NSCLC after curative surgery and the clinical outcomes of adjuvant chemotherapy. Next-generation sequencing technique will be used to examine the circulating tumor DNA (ctDNA) from MRD of 150 postoperative patients with stage IB-IIA NSCLC who received adjuvant chemotherapy.

Description:

Minimal residual disease (MRD) refers to the small number of malignant cells that remain after curative treatments (curative intent surgical resection, radiotherapy, and/or chemotherapy). MRD is common in patients with blood cancer, and is known to be associated with recurrence and poor prognosis. Recent studies also reported that MRD-negative in postoperative solid tumors such as colorectal/colon cancer and breast cancer is associated with better survival outcomes. However, the clinical values of MRD monitoring for adjuvant therapy in postoperative NSCLC remain inadequate.

Circulating tumor DNA (ctDNA), a type of cell-free DNA, refers to the DNA fragments that are derived from tumor cells and circulate in the blood. Recently, next-generation sequencing (NGS) was successfully applied to monitor NPM1, RUNX1 and FLT3 mutations in multiple myeloma. Thus, NGS technique is a promising tool for sensitive MRD monitoring, which provides the ctDNA profiling from MRD, and then provides future decision-making treatment for postoperative NSCLC patients. Thus, this clinical study aims to monitor the ctDNA status of MRD, and to explore the clinical value of MRD monitoring in decision-making adjuvant therapy for patients with stage IB-IIA NSCLC after curative surgery.

A total of 150 patients with primary curable stage IB-IIA NSCLC will be recruited in this clinical trial. The following samples will be collected from each patient including 1) preoperative blood samples; 2) surgical tissue samples; 3) blood samples 3-7 days after surgery; 4) blood samples every 3-6 month during adjuvant chemotherapy; and 5) white blood control samples. In addition, demographic and tumor characteristics of the patients will be collected for subsequent analysis, including age, sex, tumor stage, pathological stage, disease couse time, PS score, etc. NGS will be used to analyze the whole exons of potential driver genes to obtain the MRD status. Statistical analyses will be performed to analyze the survival outcomes of MRD-positive and MRD-negative group and to explore the clinical value of MRD monitoring for adjuvant therapy in postoperative NSCLC.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 2024
• Est. primary completion date: September 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Patients aged between 18 and 70 years

• Histological diagnosis of primary NSCLC

• Patients received curative surgery for primary NSCLC

• Tumor stage IB-IIA after curative-intent surgical resection

• ECOG score: 0-1

• Participant is willing to use an acceptable form of contraception during the study.

• Participant is willing and able to give informed consent for participation in the study.

Exclusion Criteria:

• The patient has received neoadjuvant therapy, including radiotherapy and chemotherapy, targeted therapy and immunotherapy

• Patients are unwilling or unable to receive the curative-intent resection

• Patients have or have had history of malignant tumor

• Patients who suffer from severe uncontrolled disease that require systemic treatment or considered unsuitable for participating this trial due to other reasons by the investigator

• Patients with severe gastrointestinal dysfunction, cardiac dysfunction, interstitial lung disease, etc.

• Laboratory test results showed inadequate bone marrow or organ function

• Blood transfusion during or within 2 weeks before the surgery

• History of alcohol abuse or drug overdose

• Pregnant or breastfeeding women

• Patients who are currently or have participated in any other anti-tumor clinical trials

• Inadequate baseline data, such as preoperative and postoperative blood samples (Lack of 2 consecutive blood test or a total of 3 blood samples), surgical tumor tissues, and ctDNA test.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Chemotherapy, Adjuvant
• Circulating Tumor DNA
• Neoplasm, Residual
• Next-Generation Sequencing

Intervention

Drug:
• Adjuvants, Pharmaceutic
Patients with stage IB-IIA NSCLC after curative surgery were treated with adjuvant chemotherapy. The blood samples of the patients before and after adjuvant chemotherapy will be collected to examine the MRD status

Locations

Country	Name	City	State
China	The Second Affiliated The Second Affiliated Hospital of Air Force Medical University (Tangdu Hospital)	Xi'an	Baqiao

Sponsors (1)

Lead Sponsor	Collaborator
Tang-Du Hospital

Country where clinical trial is conducted

China, 

References & Publications (8)

Abbosh C, Birkbak NJ, Wilson GA, Jamal-Hanjani M, Constantin T, Salari R, Le Quesne J, Moore DA, Veeriah S, Rosenthal R, Marafioti T, Kirkizlar E, Watkins TBK, McGranahan N, Ward S, Martinson L, Riley J, Fraioli F, Al Bakir M, Grönroos E, Zambrana F, Endo — View Citation

Chin RI, Chen K, Usmani A, Chua C, Harris PK, Binkley MS, Azad TD, Dudley JC, Chaudhuri AA. Detection of Solid Tumor Molecular Residual Disease (MRD) Using Circulating Tumor DNA (ctDNA). Mol Diagn Ther. 2019 Jun;23(3):311-331. doi: 10.1007/s40291-019-0039 — View Citation

Garcia-Murillas I, Schiavon G, Weigelt B, Ng C, Hrebien S, Cutts RJ, Cheang M, Osin P, Nerurkar A, Kozarewa I, Garrido JA, Dowsett M, Reis-Filho JS, Smith IE, Turner NC. Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. S — View Citation

Olsson E, Winter C, George A, Chen Y, Howlin J, Tang MH, Dahlgren M, Schulz R, Grabau D, van Westen D, Fernö M, Ingvar C, Rose C, Bendahl PO, Rydén L, Borg Å, Gruvberger-Saal SK, Jernström H, Saal LH. Serial monitoring of circulating tumor DNA in patients — View Citation

Reinert T, Henriksen TV, Christensen E, Sharma S, Salari R, Sethi H, Knudsen M, Nordentoft I, Wu HT, Tin AS, Heilskov Rasmussen M, Vang S, Shchegrova S, Frydendahl Boll Johansen A, Srinivasan R, Assaf Z, Balcioglu M, Olson A, Dashner S, Hafez D, Navarro S — View Citation

Rolfo C, Castiglia M, Hong D, Alessandro R, Mertens I, Baggerman G, Zwaenepoel K, Gil-Bazo I, Passiglia F, Carreca AP, Taverna S, Vento R, Santini D, Peeters M, Russo A, Pauwels P. Liquid biopsies in lung cancer: the new ambrosia of researchers. Biochim B — View Citation

Sausen M, Phallen J, Adleff V, Jones S, Leary RJ, Barrett MT, Anagnostou V, Parpart-Li S, Murphy D, Kay Li Q, Hruban CA, Scharpf R, White JR, O'Dwyer PJ, Allen PJ, Eshleman JR, Thompson CB, Klimstra DS, Linehan DC, Maitra A, Hruban RH, Diaz LA Jr, Von Hof — View Citation

Tie J, Cohen JD, Wang Y, Christie M, Simons K, Lee M, Wong R, Kosmider S, Ananda S, McKendrick J, Lee B, Cho JH, Faragher I, Jones IT, Ptak J, Schaeffer MJ, Silliman N, Dobbyn L, Li L, Tomasetti C, Papadopoulos N, Kinzler KW, Vogelstein B, Gibbs P. Circul — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	3-year DFS rate	DFS defined as the time from randomization to occurrence of any of the following events, whichever occurs first: Locoregional recurrence or distant metastases as determined by an independent central radiology assessment.; Occurrence of the second primary (same or other) cancer as determined by an independent central radiology assessment.; Death from any cause. Loss to follow-up is censored.	3 years
Secondary	ctDNA status	Change of Circulating tumor DNA (ctDNA) status (every 3 months)	Through study completion, up to 5 years
Secondary	TEAE	Occurrence of treatment emergent adverse event (TEAE)	Through study completion, up to 3 years
Secondary	IMP	Occurrence of dose reduction and discontinuation of IMP due to a TEAE	Through study completion, up to 3 years
Secondary	Overall survival	Follow-up of the patients will be conducted to analyze 3-year and 5-year overall survival	3 years and 5 years