Clinical Value of MRD Monitoring for Adjuvant Therapy in Postoperative NSCLC
9. prosince 2021 aktualizováno: Tang-Du Hospital
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
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.
Přehled studie
Postavení
Nábor
Podmínky
Intervence / Léčba
Detailní popis
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.
Typ studie
Pozorovací
Zápis (Očekávaný)
150
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní kontakt
- Jméno: Yunfeng Ni
- Telefonní číslo: +86 13772088014
- E-mail: 264246623@qq.com
Studijní místa
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Baqiao
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Xi'an, Baqiao, Čína, 710038
- Nábor
- The Second Affiliated The Second Affiliated Hospital of Air Force Medical University (Tangdu Hospital)
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Kontakt:
- Yunfeng Ni
- Telefonní číslo: +86 13772088014
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Vrchní vyšetřovatel:
- Tao Jiang, MD
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Dílčí vyšetřovatel:
- Yunfeng Ni, MD
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Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
18 let až 70 let (Dospělý, Starší dospělý)
Přijímá zdravé dobrovolníky
Ne
Pohlaví způsobilá ke studiu
Všechno
Metoda odběru vzorků
Vzorek nepravděpodobnosti
Studijní populace
Patents with histologically confirmed primary NSCLC, stage IB-IIA, aged 18-70 years
Popis
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.
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Observační modely: Kohorta
- Časové perspektivy: Budoucí
Kohorty a intervence
Skupina / kohorta |
Intervence / Léčba |
|---|---|
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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.
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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
Ostatní jména:
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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.
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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
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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3-year DFS rate
Časové okno: 3 years
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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
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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ctDNA status
Časové okno: Through study completion, up to 5 years
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Change of Circulating tumor DNA (ctDNA) status (every 3 months)
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Through study completion, up to 5 years
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TEAE
Časové okno: Through study completion, up to 3 years
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Occurrence of treatment emergent adverse event (TEAE)
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Through study completion, up to 3 years
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IMP
Časové okno: Through study completion, up to 3 years
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Occurrence of dose reduction and discontinuation of IMP due to a TEAE
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Through study completion, up to 3 years
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Overall survival
Časové okno: 3 years and 5 years
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Follow-up of the patients will be conducted to analyze 3-year and 5-year overall survival
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3 years and 5 years
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Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Sponzor
Vyšetřovatelé
- Vrchní vyšetřovatel: Tao Jiang, Department of Thoracic Surgery, Tangdu Hospital, the Fourth Military Medical University
Publikace a užitečné odkazy
Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.
Obecné publikace
- 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. Erratum In: Biochim Biophys Acta. 2015 Jan; 1855(1):17. Santini, Daniele [added].
- 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.
- 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. Erratum In: Nature. 2017 Dec 20;:
- 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. Erratum In: JAMA Oncol. 2019 Dec 1;5(12):1811.
- 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. Erratum In: JAMA Oncol. 2019 Jun 13;:
- 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.
- 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.
- 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.
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia (Aktuální)
30. září 2021
Primární dokončení (Očekávaný)
1. září 2023
Dokončení studie (Očekávaný)
1. prosince 2024
Termíny zápisu do studia
První předloženo
5. listopadu 2021
První předloženo, které splnilo kritéria kontroly kvality
9. prosince 2021
První zveřejněno (Aktuální)
22. prosince 2021
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
22. prosince 2021
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
9. prosince 2021
Naposledy ověřeno
1. prosince 2021
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- 777436
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Ne
Popis plánu IPD
The trial is recruiting patients
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Ne
Studuje produkt zařízení regulovaný americkým úřadem FDA
Ne
produkt vyrobený a vyvážený z USA
Ne
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .