Clinical Value of MRD Monitoring for Adjuvant Therapy in Postoperative NSCLC
9. Dezember 2021 aktualisiert von: 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.
Studienübersicht
Status
Rekrutierung
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
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.
Studientyp
Beobachtungs
Einschreibung (Voraussichtlich)
150
Kontakte und Standorte
Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.
Studienkontakt
- Name: Yunfeng Ni
- Telefonnummer: +86 13772088014
- E-Mail: 264246623@qq.com
Studienorte
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Baqiao
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Xi'an, Baqiao, China, 710038
- Rekrutierung
- The Second Affiliated The Second Affiliated Hospital of Air Force Medical University (Tangdu Hospital)
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Kontakt:
- Yunfeng Ni
- Telefonnummer: +86 13772088014
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Hauptermittler:
- Tao Jiang, MD
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Unterermittler:
- Yunfeng Ni, MD
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Teilnahmekriterien
Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.
Zulassungskriterien
Studienberechtigtes Alter
18 Jahre bis 70 Jahre (Erwachsene, Älterer Erwachsener)
Akzeptiert gesunde Freiwillige
Nein
Studienberechtigte Geschlechter
Alle
Probenahmeverfahren
Nicht-Wahrscheinlichkeitsprobe
Studienpopulation
Patents with histologically confirmed primary NSCLC, stage IB-IIA, aged 18-70 years
Beschreibung
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.
Studienplan
Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.
Wie ist die Studie aufgebaut?
Designdetails
- Beobachtungsmodelle: Kohorte
- Zeitperspektiven: Interessent
Kohorten und Interventionen
Gruppe / Kohorte |
Intervention / Behandlung |
|---|---|
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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
Andere Namen:
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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
Andere Namen:
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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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3-year DFS rate
Zeitfenster: 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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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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ctDNA status
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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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Mitarbeiter und Ermittler
Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.
Sponsor
Ermittler
- Hauptermittler: Tao Jiang, Department of Thoracic Surgery, Tangdu Hospital, the Fourth Military Medical University
Publikationen und hilfreiche Links
Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.
Allgemeine Veröffentlichungen
- 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.
Studienaufzeichnungsdaten
Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.
Haupttermine studieren
Studienbeginn (Tatsächlich)
30. September 2021
Primärer Abschluss (Voraussichtlich)
1. September 2023
Studienabschluss (Voraussichtlich)
1. Dezember 2024
Studienanmeldedaten
Zuerst eingereicht
5. November 2021
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
9. Dezember 2021
Zuerst gepostet (Tatsächlich)
22. Dezember 2021
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
22. Dezember 2021
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
9. Dezember 2021
Zuletzt verifiziert
1. Dezember 2021
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- 777436
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
Nein
Beschreibung des IPD-Plans
The trial is recruiting patients
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Nein
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
Nein
Produkt, das in den USA hergestellt und aus den USA exportiert wird
Nein
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