The Predictive Value of Guangzhou Panel for Recurrence in Early-stage Colorectal Cancer
19 aprile 2019 aggiornato da: Sixth Affiliated Hospital, Sun Yat-sen University
This study aims to evaluate the predictive value of a four-gene methylation assay called Guangzhou Panel in early-stage colorectal cancer.
Patients will be divided into two groups: high risk group and low risk group.
The primary endpoint is 5 year disease free survival (DFS).
Panoramica dello studio
Stato
Non ancora reclutamento
Condizioni
Intervento / Trattamento
Descrizione dettagliata
The current risk stratification system defined by clinicopathological features does not identify the risk of disease recurrence in patients with early-stage colorectal cancer (CRC) with optimal accuracy. The investigators aimed to investigate whether the epigenetic alterations could serve as novel prognostic biomarkers that would improve the accuracy of the current primary tumor, regional nodes, metastasis (TNM) staging system.
In the current study, the Investigators have analyzed the genome-wide methylation status of cytosine-phosphate-guanosine (CpG) sites using Infinium MethylationEPIC array in primary tumor and adjacent normal samples from 23 recurrent and 22 recurrence-free stage I and II CRC patients to identify potential methylation markers for disease-free survival (DFS). The prognostic value of the candidate biomarkers has been evaluated in a training cohort (n=174) and an independent validation cohort (n=267), and is to be validated in a prospective cohort (estimated n=287).
Comprehensive data analysis identified a subset of methylated CpG loci that associated with a high risk of recurrence. Methylated CpGs in four genes were significantly associated with DFS in multivariate analysis in both training and validation cohort. Moreover, Hypermethylated Genes Counts panel using these four markers showed a higher prognostic value than any clinicopathological factor, current molecular biomarkers or single methylated CpG marker alone in the training and validation cohorts. This four-gene methylation assay is defined as Guangzhou Panel.
The investigators aim to conduct a prospective observational study to evaluate the predictive value of Guangzhou Panel in early-stage colorectal cancer. A total of 287 patients with pathologically verified stage I-II CRC and underwent surgical resection are expected to be recruited in our study. These patients will be divided into high-risk group and low-risk group and will be followed up at least 5 years. The primary endpoint is 5-year disease free survival (DFS). The prognostic strength of candidate biomarkers was adjusted in multivariate Cox regression models including multiple biomarkers and clinicopathologic variables.
Tipo di studio
Osservativo
Iscrizione (Anticipato)
287
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Contatto studio
- Nome: Yanxin Luo, MD,PhD
- Numero di telefono: +86-13826190263
- Email: luoyx25@mail.sysu.edu.cn
Backup dei contatti dello studio
- Nome: Du Cai, MD
- Numero di telefono: +86-18819481550
- Email: caid6@mail2.sysu.edu.cn
Luoghi di studio
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Guangdong
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Guangzhou, Guangdong, Cina, 510655
- The Sixth Affiliate Hospital of Sun Yat-Sen University
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Contatto:
- Du Cai, MD
- Numero di telefono: +86-18819481550
- Email: caid6@mail2.sysu.edu.cn
-
Contatto:
- Yanxin Luo, PhD,MD
- Numero di telefono: +86-13826190263
- Email: luoyx25@mail.sysu.edu.cn
-
-
Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
Da 40 anni a 70 anni (Adulto, Adulto più anziano)
Accetta volontari sani
No
Sessi ammissibili allo studio
Tutto
Metodo di campionamento
Campione non probabilistico
Popolazione di studio
patients that had pathologically verified stage I-II CRC and underwent surgical resection in Sixth Affiliate Hospital of Sun Yat-sen University
Descrizione
Inclusion Criteria:
- TNM stage I-II (T1-4N0M0) colorectal cancer cases
- receive radical surgical resection
- have completed data of tumor location, histological type, behavioral characteristics or TNM staging
- have tumor specimens and either a valid microsatellite instability (MSI) or immuno-histochemistry (IHC) data
- have valid V-raf murine sarcoma viral oncogene homolog B1 (BRAF), kirsten rat sarcoma viral oncogene (KRAS), CpG island methylator phenotype (CIMP) results
- have at least 4 years of follow-up
- have valid time to local recurrence/metastasis in follow-up
- have clinical/treatment record data and valid preoperative status of intestinal obstruction or perforation (IOP), counts of lymph node removed in surgical resection.
Exclusion Criteria:
- have had a previous diagnosis of any cancer or presence of any tumor other than the CRC
- have had inflammatory bowel disease
- have had hereditary colorectal cancer syndromes, including Familial adenomatous polyposis, mutyh (MYH)-associated polyposis, Peutz-Jeghers syndrome, Juvenile polyposis coli, phosphate and tension homology deleted on chromosome ten (PTEN) tumor-hamartoma syndromes, Lynch Syndrome, and Familial Colorectal Cancer Type X.
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
Coorti e interventi
Gruppo / Coorte |
Intervento / Trattamento |
|---|---|
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high-risk group
patients with any of the four genes hypermethylated
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detecting the methylation status of colorectal cancer specimen
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low-risk group
patients with none of the four genes hypermethylated
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detecting the methylation status of colorectal cancer specimen
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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disease free survival
Lasso di tempo: From date of operation until the date of first recurrence or date of death from any cause, whichever came first, assessed up to 5 years
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the length of time after primary treatment for a cancer ends that the patient survives without any signs or symptoms of that cancer
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From date of operation until the date of first recurrence or date of death from any cause, whichever came first, assessed up to 5 years
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Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Investigatori
- Investigatore principale: Yanxin Luo, MD,PhD, The Sixth Affiliated Hospital, Sun Yat-sen University
Pubblicazioni e link utili
La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.
Pubblicazioni generali
- Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018 Jan;68(1):7-30. doi: 10.3322/caac.21442. Epub 2018 Jan 4.
- Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet. 2014 Apr 26;383(9927):1490-1502. doi: 10.1016/S0140-6736(13)61649-9. Epub 2013 Nov 11.
- Feinberg AP. The Key Role of Epigenetics in Human Disease Prevention and Mitigation. N Engl J Med. 2018 Apr 5;378(14):1323-1334. doi: 10.1056/NEJMra1402513. No abstract available.
- Ribic CM, Sargent DJ, Moore MJ, Thibodeau SN, French AJ, Goldberg RM, Hamilton SR, Laurent-Puig P, Gryfe R, Shepherd LE, Tu D, Redston M, Gallinger S. Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med. 2003 Jul 17;349(3):247-57. doi: 10.1056/NEJMoa022289.
- Quasar Collaborative Group; Gray R, Barnwell J, McConkey C, Hills RK, Williams NS, Kerr DJ. Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study. Lancet. 2007 Dec 15;370(9604):2020-9. doi: 10.1016/S0140-6736(07)61866-2.
- O'Connor ES, Greenblatt DY, LoConte NK, Gangnon RE, Liou JI, Heise CP, Smith MA. Adjuvant chemotherapy for stage II colon cancer with poor prognostic features. J Clin Oncol. 2011 Sep 1;29(25):3381-8. doi: 10.1200/JCO.2010.34.3426. Epub 2011 Jul 25.
- Morris EJ, Maughan NJ, Forman D, Quirke P. Who to treat with adjuvant therapy in Dukes B/stage II colorectal cancer? The need for high quality pathology. Gut. 2007 Oct;56(10):1419-25. doi: 10.1136/gut.2006.116830. Epub 2007 May 9.
- Kennedy RD, Bylesjo M, Kerr P, Davison T, Black JM, Kay EW, Holt RJ, Proutski V, Ahdesmaki M, Farztdinov V, Goffard N, Hey P, McDyer F, Mulligan K, Mussen J, O'Brien E, Oliver G, Walker SM, Mulligan JM, Wilson C, Winter A, O'Donoghue D, Mulcahy H, O'Sullivan J, Sheahan K, Hyland J, Dhir R, Bathe OF, Winqvist O, Manne U, Shanmugam C, Ramaswamy S, Leon EJ, Smith WI Jr, McDermott U, Wilson RH, Longley D, Marshall J, Cummins R, Sargent DJ, Johnston PG, Harkin DP. Development and independent validation of a prognostic assay for stage II colon cancer using formalin-fixed paraffin-embedded tissue. J Clin Oncol. 2011 Dec 10;29(35):4620-6. doi: 10.1200/JCO.2011.35.4498. Epub 2011 Nov 7.
- Esteller M. Epigenetics in cancer. N Engl J Med. 2008 Mar 13;358(11):1148-59. doi: 10.1056/NEJMra072067. No abstract available.
- Weisenberger DJ, Siegmund KD, Campan M, Young J, Long TI, Faasse MA, Kang GH, Widschwendter M, Weener D, Buchanan D, Koh H, Simms L, Barker M, Leggett B, Levine J, Kim M, French AJ, Thibodeau SN, Jass J, Haile R, Laird PW. CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet. 2006 Jul;38(7):787-93. doi: 10.1038/ng1834. Epub 2006 Jun 25.
- Brock MV, Hooker CM, Ota-Machida E, Han Y, Guo M, Ames S, Glockner S, Piantadosi S, Gabrielson E, Pridham G, Pelosky K, Belinsky SA, Yang SC, Baylin SB, Herman JG. DNA methylation markers and early recurrence in stage I lung cancer. N Engl J Med. 2008 Mar 13;358(11):1118-28. doi: 10.1056/NEJMoa0706550.
- Hinoue T, Weisenberger DJ, Lange CP, Shen H, Byun HM, Van Den Berg D, Malik S, Pan F, Noushmehr H, van Dijk CM, Tollenaar RA, Laird PW. Genome-scale analysis of aberrant DNA methylation in colorectal cancer. Genome Res. 2012 Feb;22(2):271-82. doi: 10.1101/gr.117523.110. Epub 2011 Jun 9.
- Luo Y, Wong CJ, Kaz AM, Dzieciatkowski S, Carter KT, Morris SM, Wang J, Willis JE, Makar KW, Ulrich CM, Lutterbaugh JD, Shrubsole MJ, Zheng W, Markowitz SD, Grady WM. Differences in DNA methylation signatures reveal multiple pathways of progression from adenoma to colorectal cancer. Gastroenterology. 2014 Aug;147(2):418-29.e8. doi: 10.1053/j.gastro.2014.04.039. Epub 2014 Apr 30.
- Martinez-Cardus A, Moran S, Musulen E, Moutinho C, Manzano JL, Martinez-Balibrea E, Tierno M, Elez E, Landolfi S, Lorden P, Arribas C, Muller F, Bock C, Tabernero J, Esteller M. Epigenetic Homogeneity Within Colorectal Tumors Predicts Shorter Relapse-Free and Overall Survival Times for Patients With Locoregional Cancer. Gastroenterology. 2016 Nov;151(5):961-972. doi: 10.1053/j.gastro.2016.08.001. Epub 2016 Aug 10.
- Pidsley R, Zotenko E, Peters TJ, Lawrence MG, Risbridger GP, Molloy P, Van Djik S, Muhlhausler B, Stirzaker C, Clark SJ. Critical evaluation of the Illumina MethylationEPIC BeadChip microarray for whole-genome DNA methylation profiling. Genome Biol. 2016 Oct 7;17(1):208. doi: 10.1186/s13059-016-1066-1.
- Moran S, Arribas C, Esteller M. Validation of a DNA methylation microarray for 850,000 CpG sites of the human genome enriched in enhancer sequences. Epigenomics. 2016 Mar;8(3):389-99. doi: 10.2217/epi.15.114. Epub 2015 Dec 17.
Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio (Anticipato)
30 aprile 2019
Completamento primario (Anticipato)
30 aprile 2021
Completamento dello studio (Anticipato)
31 dicembre 2026
Date di iscrizione allo studio
Primo inviato
14 aprile 2019
Primo inviato che soddisfa i criteri di controllo qualità
19 aprile 2019
Primo Inserito (Effettivo)
22 aprile 2019
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
22 aprile 2019
Ultimo aggiornamento inviato che soddisfa i criteri QC
19 aprile 2019
Ultimo verificato
1 marzo 2019
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Malattie dell'apparato digerente
- Processi patologici
- Neoplasie
- Neoplasie per sede
- Attributi della malattia
- Neoplasie gastrointestinali
- Neoplasie dell'apparato digerente
- Malattie gastrointestinali
- Malattie del colon
- Malattie intestinali
- Neoplasie intestinali
- Malattie del retto
- Neoplasie colorettali
- Ricorrenza
Altri numeri di identificazione dello studio
- Luo-20190326
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
INDECISO
Descrizione del piano IPD
Our DNA methylation panel is applying for patent protection, therefore we plan to keep the data private for the time being.
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
No
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
No
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .