Clinical Value of MRD Monitoring for Adjuvant Therapy in Postoperative NSCLC

NCT05167604 | Unknown DMC

• 1 other identifier: 777436
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

non-small cell lung cancer; next-generation sequencing; adjuvant chemotherapy; minimal residual disease; circulating tumor DNA

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• ctDNA status

  Through study completion, up to 5 years

• TEAE

  Through study completion, up to 3 years

• IMP

  Through study completion, up to 3 years

• Overall survival

  3 years and 5 years

Study Arms (2)

MRD-positive Cohort

ctDNA positivity in pretreatment and posttreatment plasma samples was defined by accessing the presence of one or more mutations identified in match tumor samples. A mutation was considered present when at least one consensus read contained the mutation and passed the local polishing pipeline. The MRD positive cohort was randomly divided into two groups, one group for interventional treatment and the other group for observation.

Drug: Adjuvants, Pharmaceutic

MRD-negative Cohort

ctDNA negative in pretreatment and posttreatment plasma samples was defined by accessing the presence of no mutation identified in match tumor samples. According to the clinical prognostic characteristics of the MRD negative group, the clinician decides to observe or treat.

Drug: Adjuvants, Pharmaceutic

Interventions

Adjuvants, Pharmaceutic DRUG

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

Also known as: adjuvant chemotherapy

MRD-negative Cohort; MRD-positive Cohort

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patents with histologically confirmed primary NSCLC, stage IB-IIA, aged 18-70 years

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tang-Du Hospital: lead

Study Sites (1)

The Second Affiliated The Second Affiliated Hospital of Air Force Medical University (Tangdu Hospital)

Xi'an, Baqiao, 710038, China

RECRUITING

Related Publications (8)

• 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 Biophys Acta. 2014 Dec;1846(2):539-46. doi: 10.1016/j.bbcan.2014.10.001. Epub 2014 Oct 16.

  PMID: 25444714 RESULT

• 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/s40291-019-00390-5.

  PMID: 30941670 RESULT

• 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, Gronroos E, Zambrana F, Endozo R, Bi WL, Fennessy FM, Sponer N, Johnson D, Laycock J, Shafi S, Czyzewska-Khan J, Rowan A, Chambers T, Matthews N, Turajlic S, Hiley C, Lee SM, Forster MD, Ahmad T, Falzon M, Borg E, Lawrence D, Hayward M, Kolvekar S, Panagiotopoulos N, Janes SM, Thakrar R, Ahmed A, Blackhall F, Summers Y, Hafez D, Naik A, Ganguly A, Kareht S, Shah R, Joseph L, Marie Quinn A, Crosbie PA, Naidu B, Middleton G, Langman G, Trotter S, Nicolson M, Remmen H, Kerr K, Chetty M, Gomersall L, Fennell DA, Nakas A, Rathinam S, Anand G, Khan S, Russell P, Ezhil V, Ismail B, Irvin-Sellers M, Prakash V, Lester JF, Kornaszewska M, Attanoos R, Adams H, Davies H, Oukrif D, Akarca AU, Hartley JA, Lowe HL, Lock S, Iles N, Bell H, Ngai Y, Elgar G, Szallasi Z, Schwarz RF, Herrero J, Stewart A, Quezada SA, Peggs KS, Van Loo P, Dive C, Lin CJ, Rabinowitz M, Aerts HJWL, Hackshaw A, Shaw JA, Zimmermann BG; TRACERx consortium; PEACE consortium; Swanton C. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature. 2017 Apr 26;545(7655):446-451. doi: 10.1038/nature22364.

  PMID: 28445469 RESULT

• 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. Circulating Tumor DNA Analyses as Markers of Recurrence Risk and Benefit of Adjuvant Therapy for Stage III Colon Cancer. JAMA Oncol. 2019 Dec 1;5(12):1710-1717. doi: 10.1001/jamaoncol.2019.3616.

  PMID: 31621801 RESULT

• 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, Goel S, Rabinowitz M, Billings P, Sigurjonsson S, Dyrskjot L, Swenerton R, Aleshin A, Laurberg S, Husted Madsen A, Kannerup AS, Stribolt K, Palmelund Krag S, Iversen LH, Gotschalck Sunesen K, Lin CJ, Zimmermann BG, Lindbjerg Andersen C. Analysis of Plasma Cell-Free DNA by Ultradeep Sequencing in Patients With Stages I to III Colorectal Cancer. JAMA Oncol. 2019 Aug 1;5(8):1124-1131. doi: 10.1001/jamaoncol.2019.0528.

  PMID: 31070691 RESULT

• 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. Sci Transl Med. 2015 Aug 26;7(302):302ra133. doi: 10.1126/scitranslmed.aab0021.

  PMID: 26311728 RESULT

• Olsson E, Winter C, George A, Chen Y, Howlin J, Tang MH, Dahlgren M, Schulz R, Grabau D, van Westen D, Ferno M, Ingvar C, Rose C, Bendahl PO, Ryden L, Borg A, Gruvberger-Saal SK, Jernstrom H, Saal LH. Serial monitoring of circulating tumor DNA in patients with primary breast cancer for detection of occult metastatic disease. EMBO Mol Med. 2015 Aug;7(8):1034-47. doi: 10.15252/emmm.201404913.

  PMID: 25987569 RESULT

• 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 Hoff DD, Johansen JS, Drebin JA, Velculescu VE. Clinical implications of genomic alterations in the tumour and circulation of pancreatic cancer patients. Nat Commun. 2015 Jul 7;6:7686. doi: 10.1038/ncomms8686.

  PMID: 26154128 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Circular DNA from the blood samples of NSCLC patients before and after adjuvant chemotherapy were collected and examined by NGS

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasm, Residual

Interventions

Adjuvants, Pharmaceutic; Chemotherapy, Adjuvant

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pharmaceutic Aids; Pharmaceutical Preparations; Specialty Uses of Chemicals; Chemical Actions and Uses; Combined Modality Therapy; Therapeutics; Drug Therapy

Study Officials

• Tao Jiang

  Department of Thoracic Surgery, Tangdu Hospital, the Fourth Military Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yunfeng Ni

CONTACT

+86 13772088014; 264246623@qq.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 24 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2021
• First Posted: December 22, 2021
• Study Start: September 30, 2021
• Primary Completion: September 1, 2023
• Study Completion: December 1, 2024
• Last Updated: December 22, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)