Molecular Profiling of Colorectal Cancer

Molecular Profiling of Colorectal Cancer: A Translational Research Study With a Next Generation Sequencing Panel.

In this translational research study, Formalin-Fixed-Paraffin-Embedded (FFPE) tumor tissue blocks from patients with early-stage (II-III) colorectal cancer will be assessed for a comprehensive cancer gene panel from NIPD Genetics (https://www.nipd.com/) targeting regions in 37 clinically relevant cancer genes.

The colorectal cancer panel includes an extended list of clinically relevant genes, designed to target clinically actionable and clinically significant mutations that will provide physicians with genetic information regarding a) prediction of the patient's response to targeted therapy, b) prognosis, that is, prediction of clinical outcome, c) diagnosis and molecular classification of colorectal cancer.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Colon Cancer; Colon Adenocarcinoma
• Intervention / Treatment: Diagnostic test: Gene panel

• Study Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

• Study Contact: Name: George Papaxoinis; Phone Number: +302106409000; Email: georgexoinis@gmail.com

Study Locations

• Greece
  • Athens, Greece, 11526
    • Recruiting
    • Hellenic Cooperative Oncology Group
    • Contact: Hellenic Cooperative O Group; Phone Number: 6977018142; Email: georgexoinis@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients who underwent surgical resection of early-stage (II-III) colorectal cancer

Description

Inclusion Criteria:

• Surgically resected early-stage (II-III) colorectal cancer
• Availability of biological material

Exclusion Criteria:

• Metastatic disease (stage IV) at initial diagnosis

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
association between gene mutational status and overall survival	the time from diagnosis to the date of death (from any cause). Alive patients and patients lost to follow-up will be censored at the date of last follow-up	24 months
association between gene mutational status and disease-free survival	the time from colorectal cancer diagnosis to the first date of documented disease progression, death or last contact, whichever occurs first	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Descriptives	Association of any gene mutation tumor pathological stages.	24 months
Descriptives	Association of any gene mutation tumor budding.	24 months
Descriptives	Association of any gene mutation with microstatellite instability.	24 months

Collaborators and Investigators

• Sponsor: Hellenic Cooperative Oncology Group
• Investigators: Study Chair: George Fountzilas, Prof, Hellenic Cooperative Oncology Group

Publications and helpful links

General Publications

• Stratton MR, Campbell PJ, Futreal PA. The cancer genome. Nature. 2009 Apr 9;458(7239):719-24. doi: 10.1038/nature07943.
• Dekker E, Tanis PJ, Vleugels JLA, Kasi PM, Wallace MB. Colorectal cancer. Lancet. 2019 Oct 19;394(10207):1467-1480. doi: 10.1016/S0140-6736(19)32319-0.
• Seufferlein T, Simoes C, Kude F, Ettrich TJ. Molecular Approaches to Metastatic Colorectal Cancer: Better Diagnosis - Better Treatment? Visc Med. 2019 Aug;35(4):259-264. doi: 10.1159/000500617. Epub 2019 Jul 11.
• Khan K, Valeri N, Dearman C, Rao S, Watkins D, Starling N, Chau I, Cunningham D. Targeting EGFR pathway in metastatic colorectal cancer- tumour heterogeniety and convergent evolution. Crit Rev Oncol Hematol. 2019 Nov;143:153-163. doi: 10.1016/j.critrevonc.2019.09.001. Epub 2019 Sep 7.
• Cohen R, Rousseau B, Vidal J, Colle R, Diaz LA Jr, Andre T. Immune Checkpoint Inhibition in Colorectal Cancer: Microsatellite Instability and Beyond. Target Oncol. 2020 Feb;15(1):11-24. doi: 10.1007/s11523-019-00690-0.
• Caputo F, Santini C, Bardasi C, Cerma K, Casadei-Gardini A, Spallanzani A, Andrikou K, Cascinu S, Gelsomino F. BRAF-Mutated Colorectal Cancer: Clinical and Molecular Insights. Int J Mol Sci. 2019 Oct 28;20(21):5369. doi: 10.3390/ijms20215369.
• Oh HH, Joo YE. Novel biomarkers for the diagnosis and prognosis of colorectal cancer. Intest Res. 2020 Apr;18(2):168-183. doi: 10.5217/ir.2019.00080. Epub 2019 Nov 30.
• De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G, Kalogeras KT, Kotoula V, Papamichael D, Laurent-Puig P, Penault-Llorca F, Rougier P, Vincenzi B, Santini D, Tonini G, Cappuzzo F, Frattini M, Molinari F, Saletti P, De Dosso S, Martini M, Bardelli A, Siena S, Sartore-Bianchi A, Tabernero J, Macarulla T, Di Fiore F, Gangloff AO, Ciardiello F, Pfeiffer P, Qvortrup C, Hansen TP, Van Cutsem E, Piessevaux H, Lambrechts D, Delorenzi M, Tejpar S. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol. 2010 Aug;11(8):753-62. doi: 10.1016/S1470-2045(10)70130-3. Epub 2010 Jul 8.
• Strimpakos A, Pentheroudakis G, Kotoula V, De Roock W, Kouvatseas G, Papakostas P, Makatsoris T, Papamichael D, Andreadou A, Sgouros J, Zizi-Sermpetzoglou A, Kominea A, Televantou D, Razis E, Galani E, Pectasides D, Tejpar S, Syrigos K, Fountzilas G. The prognostic role of ephrin A2 and endothelial growth factor receptor pathway mediators in patients with advanced colorectal cancer treated with cetuximab. Clin Colorectal Cancer. 2013 Dec;12(4):267-274.e2. doi: 10.1016/j.clcc.2013.07.001. Epub 2013 Sep 17.
• Pentheroudakis G, Kotoula V, De Roock W, Kouvatseas G, Papakostas P, Makatsoris T, Papamichael D, Xanthakis I, Sgouros J, Televantou D, Kafiri G, Tsamandas AC, Razis E, Galani E, Bafaloukos D, Efstratiou I, Bompolaki I, Pectasides D, Pavlidis N, Tejpar S, Fountzilas G. Biomarkers of benefit from cetuximab-based therapy in metastatic colorectal cancer: interaction of EGFR ligand expression with RAS/RAF, PIK3CA genotypes. BMC Cancer. 2013 Feb 2;13:49. doi: 10.1186/1471-2407-13-49.
• Pagani F, Randon G, Guarini V, Raimondi A, Prisciandaro M, Lobefaro R, Di Bartolomeo M, Sozzi G, de Braud F, Gasparini P, Pietrantonio F. The Landscape of Actionable Gene Fusions in Colorectal Cancer. Int J Mol Sci. 2019 Oct 25;20(21):5319. doi: 10.3390/ijms20215319.
• Itatani Y, Kawada K, Yamamoto T, Sakai Y. Resistance to Anti-Angiogenic Therapy in Cancer-Alterations to Anti-VEGF Pathway. Int J Mol Sci. 2018 Apr 18;19(4):1232. doi: 10.3390/ijms19041232.
• Pentheroudakis G, Mavroeidis L, Papadopoulou K, Koliou GA, Bamia C, Chatzopoulos K, Samantas E, Mauri D, Efstratiou I, Pectasides D, Makatsoris T, Bafaloukos D, Papakostas P, Papatsibas G, Bombolaki I, Chrisafi S, Kourea HP, Petraki K, Kafiri G, Fountzilas G, Kotoula V. Angiogenic and Antiangiogenic VEGFA Splice Variants in Colorectal Cancer: Prospective Retrospective Cohort Study in Patients Treated With Irinotecan-Based Chemotherapy and Bevacizumab. Clin Colorectal Cancer. 2019 Dec;18(4):e370-e384. doi: 10.1016/j.clcc.2019.07.007. Epub 2019 Jul 15.
• Pentheroudakis G, Kotoula V, Fountzilas E, Kouvatseas G, Basdanis G, Xanthakis I, Makatsoris T, Charalambous E, Papamichael D, Samantas E, Papakostas P, Bafaloukos D, Razis E, Christodoulou C, Varthalitis I, Pavlidis N, Fountzilas G. A study of gene expression markers for predictive significance for bevacizumab benefit in patients with metastatic colon cancer: a translational research study of the Hellenic Cooperative Oncology Group (HeCOG). BMC Cancer. 2014 Feb 20;14:111. doi: 10.1186/1471-2407-14-111.
• Koutras AK, Antonacopoulou AG, Eleftheraki AG, Dimitrakopoulos FI, Koumarianou A, Varthalitis I, Fostira F, Sgouros J, Briasoulis E, Bournakis E, Bafaloukos D, Bompolaki I, Galani E, Kalogeras KT, Pectasides D, Fountzilas G, Kalofonos HP. Vascular endothelial growth factor polymorphisms and clinical outcome in colorectal cancer patients treated with irinotecan-based chemotherapy and bevacizumab. Pharmacogenomics J. 2012 Dec;12(6):468-75. doi: 10.1038/tpj.2011.37. Epub 2011 Aug 16.
• Chin L, Gray JW. Translating insights from the cancer genome into clinical practice. Nature. 2008 Apr 3;452(7187):553-63. doi: 10.1038/nature06914.
• Forbes SA, Beare D, Boutselakis H, Bamford S, Bindal N, Tate J, Cole CG, Ward S, Dawson E, Ponting L, Stefancsik R, Harsha B, Kok CY, Jia M, Jubb H, Sondka Z, Thompson S, De T, Campbell PJ. COSMIC: somatic cancer genetics at high-resolution. Nucleic Acids Res. 2017 Jan 4;45(D1):D777-D783. doi: 10.1093/nar/gkw1121. Epub 2016 Nov 28.
• Cancer Genome Atlas Research Network; Weinstein JN, Collisson EA, Mills GB, Shaw KR, Ozenberger BA, Ellrott K, Shmulevich I, Sander C, Stuart JM. The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet. 2013 Oct;45(10):1113-20. doi: 10.1038/ng.2764.
• Landrum MJ, Lee JM, Riley GR, Jang W, Rubinstein WS, Church DM, Maglott DR. ClinVar: public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res. 2014 Jan;42(Database issue):D980-5. doi: 10.1093/nar/gkt1113. Epub 2013 Nov 14.
• Jennings LJ, Arcila ME, Corless C, Kamel-Reid S, Lubin IM, Pfeifer J, Temple-Smolkin RL, Voelkerding KV, Nikiforova MN. Guidelines for Validation of Next-Generation Sequencing-Based Oncology Panels: A Joint Consensus Recommendation of the Association for Molecular Pathology and College of American Pathologists. J Mol Diagn. 2017 May;19(3):341-365. doi: 10.1016/j.jmoldx.2017.01.011. Epub 2017 Mar 21.
• Koumbaris G, Kypri E, Tsangaras K, Achilleos A, Mina P, Neofytou M, Velissariou V, Christopoulou G, Kallikas I, Gonzalez-Linan A, Benusiene E, Latos-Bielenska A, Marek P, Santana A, Nagy N, Szell M, Laudanski P, Papageorgiou EA, Ioannides M, Patsalis PC. Cell-Free DNA Analysis of Targeted Genomic Regions in Maternal Plasma for Non-Invasive Prenatal Testing of Trisomy 21, Trisomy 18, Trisomy 13, and Fetal Sex. Clin Chem. 2016 Jun;62(6):848-55. doi: 10.1373/clinchem.2015.252502. Epub 2016 Apr 26.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2006
• Primary Completion (Anticipated): September 1, 2021
• Study Completion (Anticipated): September 1, 2022

Study Registration Dates

• First Submitted: March 12, 2021
• First Submitted That Met QC Criteria: April 26, 2021
• First Posted (Actual): April 28, 2021

Study Record Updates

• Last Update Posted (Actual): April 28, 2021
• Last Update Submitted That Met QC Criteria: April 26, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Colon; Translational research; Gene panel
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: TR6N/19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No