Early-Onset Colorectal Cancer Recurrence

Colorectal Cancer Clinical Trial

— ENCORE  

Official title:

Predicting Long-Term Recurrence-Free and Overall Survival in Early-Onset Colorectal Cancer Survivors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06271980
• Other study ID #: 23228/ENCORE
• Status: Completed
• Start date: April 15, 2023
• Est. completion date: February 1, 2024

Study information

• Verified date: March 2024
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Survivors of early-onset colorectal cancer (diagnosed before age 50) may experience colorectal cancer recurrence several years after curative-intent treatments, but clinical guidelines provide unclear guidance on endoscopic surveillance. This study aims to predict recurrence-free survival and overall survival, in survivors of early-onset colorectal cancer, using a tumor-based molecular assay based on microRNA (ribonucleic acid)

Description:

Colorectal cancer (CRC) once predominantly affected older individuals, but in recent years has witnessed a progressive increase in incidence among young adults. Once rare, early-onset colorectal cancer (EOCRC, that is, a CRC diagnosed before the age of 50) now constitutes 10-15% of all newly diagnosed CRC cases and it stands as the first cause of cancer-related death in young men in the US and the second for young women. In the wake of the increasing incidence, the growing population of EOCRC survivors introduces distinctive clinical challenges. Patients with EOCRC are hypothesized to possess a more biologically active colorectum, susceptible to malignant transformation both earlier in life and later after primary cancer. Indeed, EOCRC survivors encounter an elevated risk of disease recurrence, a risk that may manifest years after primary treatment. These considerations have prompted a trend toward offering more aggressive therapy or endoscopy surveillance, a practice however not substantiated by evidence yet. Scientific societies have also adopted a cautious stance, recognizing the elevated risk while acknowledging the absence of evidence to substantiate an intensified surveillance protocol, which might constitute overtreatment. In this research effort, the investigators will leverage machine learning to predict recurrence-free survival (RFS) and overall survival (OS) in patients cured of EOCRC. The research plan will employ three phases: 1. After a systematic discovery phase, based on small RNA sequencing, the investigators will identify a panel of candidate biomarkers. 2. The investigators will then develop an assay based on reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and train a machine-learning model to predict recurrence-free and overall survival outcomes 3. The investigators will independently validate the assay. This assay is provisionally termed "ENCORE" (Early oNset COlorectal cancer REcurrence) and will be tested for recurrence-free and overall survival outcomes up to ten years after treatment. At the end of this study, this assay will have been developed and validated to help clinical decision-making by predicting both recurrence-free and overall survival in EOCRC survivors.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 177
• Est. completion date: February 1, 2024
• Est. primary completion date: February 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Stage I, II, or III colorectal cancer (TNM classification, 8th edition) diagnosed before the age of 50
• Received standard diagnostic, staging, and therapeutic procedures as per local guidelines, received stage-specific curative-intent resection (with or without systemic therapy, as appropriate)
• Confirmed cancer-free survivors at the time of study inclusion

Exclusion Criteria:

• Hereditary colorectal cancer syndromes (identified through genetic testing)
• Inflammatory bowel diseases
• Lack of written informed consent

Related Conditions & MeSH terms

• Colorectal Adenocarcinoma
• Colorectal Cancer
• Colorectal Cancer Recurrent
• Colorectal Cancer Stage I
• Colorectal Cancer Stage II
• Colorectal Cancer Stage III
• Colorectal Neoplasms
• Recurrence

Intervention

Other:
• ENCORE
A panel of microRNA, whose expression level is tested in macro-dissected formalin-fixed and paraffin-embedded (FFPE) samples derived from the primary tumor.

Locations

Country	Name	City	State
United States	City of Hope Medical Center	Duarte	California

Sponsors (3)

Lead Sponsor	Collaborator
City of Hope Medical Center	Institute of Biomedical Research of Salamanca, Salamanca, Spain, IRCCS San Raffaele Hospital, Milan, Italy

Country where clinical trial is conducted

United States, 

References & Publications (18)

Al Maliki H, Monahan KJ. The diagnostic yield of colonoscopic surveillance following resection of early age onset colorectal cancer. United European Gastroenterol J. 2024 Jan 3. doi: 10.1002/ueg2.12516. Online ahead of print. — View Citation

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Cavestro GM, Mannucci A, Balaguer F, Hampel H, Kupfer SS, Repici A, Sartore-Bianchi A, Seppala TT, Valentini V, Boland CR, Brand RE, Buffart TE, Burke CA, Caccialanza R, Cannizzaro R, Cascinu S, Cercek A, Crosbie EJ, Danese S, Dekker E, Daca-Alvarez M, Deni F, Dominguez-Valentin M, Eng C, Goel A, Guillem JG, Houwen BBSL, Kahi C, Kalady MF, Kastrinos F, Kuhn F, Laghi L, Latchford A, Liska D, Lynch P, Malesci A, Mauri G, Meldolesi E, Moller P, Monahan KJ, Moslein G, Murphy CC, Nass K, Ng K, Oliani C, Papaleo E, Patel SG, Puzzono M, Remo A, Ricciardiello L, Ripamonti CI, Siena S, Singh SK, Stadler ZK, Stanich PP, Syngal S, Turi S, Urso ED, Valle L, Vanni VS, Vilar E, Vitellaro M, You YN, Yurgelun MB, Zuppardo RA, Stoffel EM; Associazione Italiana Familiarita Ereditarieta Tumori; Collaborative Group of the Americas on Inherited Gastrointestinal Cancer; European Hereditary Tumour Group, and the International Society for Gastrointestinal Hereditary Tumours. Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines. Clin Gastroenterol Hepatol. 2023 Mar;21(3):581-603.e33. doi: 10.1016/j.cgh.2022.12.006. Epub 2022 Dec 20. — View Citation

Chen FW, Sundaram V, Chew TA, Ladabaum U. Advanced-Stage Colorectal Cancer in Persons Younger Than 50 Years Not Associated With Longer Duration of Symptoms or Time to Diagnosis. Clin Gastroenterol Hepatol. 2017 May;15(5):728-737.e3. doi: 10.1016/j.cgh.2016.10.038. Epub 2016 Nov 14. — View Citation

Foppa C, Tamburello S, Maroli A, Carvello M, Poliani L, Laghi L, Malesci A, Montorsi M, Perea J, Spinelli A. Early age of onset is an independent predictor for worse disease-free survival in sporadic rectal cancer patients. A comparative analysis of 980 consecutive patients. Eur J Surg Oncol. 2022 Apr;48(4):857-863. doi: 10.1016/j.ejso.2021.10.021. Epub 2021 Oct 28. — View Citation

Jung G, Hernandez-Illan E, Moreira L, Balaguer F, Goel A. Epigenetics of colorectal cancer: biomarker and therapeutic potential. Nat Rev Gastroenterol Hepatol. 2020 Feb;17(2):111-130. doi: 10.1038/s41575-019-0230-y. Epub 2020 Jan 3. — View Citation

Kim SB, Lee HJ, Park SJ, Hong SP, Cheon JH, Kim WH, Kim TI. Comparison of Colonoscopy Surveillance Outcomes Between Young and Older Colorectal Cancer Patients. J Cancer Prev. 2017 Sep;22(3):159-165. doi: 10.15430/JCP.2017.22.3.159. Epub 2017 Sep 30. — View Citation

Kim TJ, Kim ER, Hong SN, Chang DK, Kim YH. Long-Term Outcome and Prognostic Factors of Sporadic Colorectal Cancer in Young Patients: A Large Institutional-Based Retrospective Study. Medicine (Baltimore). 2016 May;95(19):e3641. doi: 10.1097/MD.0000000000003641. — View Citation

Monahan KJ, Bradshaw N, Dolwani S, Desouza B, Dunlop MG, East JE, Ilyas M, Kaur A, Lalloo F, Latchford A, Rutter MD, Tomlinson I, Thomas HJW, Hill J; Hereditary CRC guidelines eDelphi consensus group. Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom Cancer Genetics Group (UKCGG). Gut. 2020 Mar;69(3):411-444. doi: 10.1136/gutjnl-2019-319915. Epub 2019 Nov 28. — View Citation

Nakamura K, Hernandez G, Sharma GG, Wada Y, Banwait JK, Gonzalez N, Perea J, Balaguer F, Takamaru H, Saito Y, Toiyama Y, Kodera Y, Boland CR, Bujanda L, Quintero E, Goel A. A Liquid Biopsy Signature for the Detection of Patients With Early-Onset Colorectal Cancer. Gastroenterology. 2022 Nov;163(5):1242-1251.e2. doi: 10.1053/j.gastro.2022.06.089. Epub 2022 Jul 16. — View Citation

Okugawa Y, Grady WM, Goel A. Epigenetic Alterations in Colorectal Cancer: Emerging Biomarkers. Gastroenterology. 2015 Oct;149(5):1204-1225.e12. doi: 10.1053/j.gastro.2015.07.011. Epub 2015 Jul 26. — View Citation

Peacock O, Vilar E, Guraieb-Trueba M, Thirumurthi S, Chang GJ, You YN. Clinically Significant Metachronous Colorectal Pathology Detected Among Young-Onset Colorectal Cancer Survivors: Implications for Post-Resection Surveillance Guidelines. Gastroenterology. 2022 Dec;163(6):1682-1684.e2. doi: 10.1053/j.gastro.2022.08.030. Epub 2022 Aug 17. No abstract available. — View Citation

Rutter MD, East J, Rees CJ, Cripps N, Docherty J, Dolwani S, Kaye PV, Monahan KJ, Novelli MR, Plumb A, Saunders BP, Thomas-Gibson S, Tolan DJM, Whyte S, Bonnington S, Scope A, Wong R, Hibbert B, Marsh J, Moores B, Cross A, Sharp L. British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland/Public Health England post-polypectomy and post-colorectal cancer resection surveillance guidelines. Gut. 2020 Feb;69(2):201-223. doi: 10.1136/gutjnl-2019-319858. Epub 2019 Nov 27. — View Citation

Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024 Jan-Feb;74(1):12-49. doi: 10.3322/caac.21820. Epub 2024 Jan 17. Erratum In: CA Cancer J Clin. 2024 Feb 16;: — View Citation

Siegel RL, Wagle NS, Cercek A, Smith RA, Jemal A. Colorectal cancer statistics, 2023. CA Cancer J Clin. 2023 May-Jun;73(3):233-254. doi: 10.3322/caac.21772. Epub 2023 Mar 1. — View Citation

Sinicrope FA. Increasing Incidence of Early-Onset Colorectal Cancer. N Engl J Med. 2022 Apr 21;386(16):1547-1558. doi: 10.1056/NEJMra2200869. No abstract available. — View Citation

You YN, Dozois EJ, Boardman LA, Aakre J, Huebner M, Larson DW. Young-onset rectal cancer: presentation, pattern of care and long-term oncologic outcomes compared to a matched older-onset cohort. Ann Surg Oncol. 2011 Sep;18(9):2469-76. doi: 10.1245/s10434-011-1674-7. Epub 2011 Mar 30. — View Citation

Zaborowski AM, Murphy B, Creavin B, Rogers AC, Kennelly R, Hanly A, Martin ST, O'Connell PR, Sheahan K, Winter DC. Clinicopathological features and oncological outcomes of patients with young-onset rectal cancer. Br J Surg. 2020 Apr;107(5):606-612. doi: 10.1002/bjs.11526. Epub 2020 Mar 9. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recurrence Free Survival	Time from disease treatment to development of recurrent colorectal cancer	Up to 120 months
Secondary	Overall Survival	Time from disease treatment to death from any cause	Up to 120 months