Polyprev: Study to Compare Fecal Immunochemical Test With Endoscopic Surveillance After Advanced Adenoma Resection in Fecal Immunochemical Test Colorectal Cancer Screening Programs.

Colorectal Cancer Clinical Trial

Official title:

Polyprev Study: Randomized, Multicenter, Controlled Trial Comparing Fecal Immunochemical Test With Endoscopic Surveillance After Advanced Adenoma Resection in Fecal Immunochemical Test Colorectal Cancer Screening Programs.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04967183
• Other study ID #: POLYPREV
• Status: Recruiting
• Phase: N/A
• Start date: June 1, 2022
• Est. completion date: June 2035

Study information

• Verified date: February 2024
• Source: Fundacin Biomedica Galicia Sur
• Contact: Joaquín Cubiella, MD PhD
• Phone: 0034988385824
• Email: joaquin.cubiella.fernandez[@]sergas.es
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Colorectal cancer (CRC) screening programs have been implemented to reduce the burden of the disease. When an advanced colonic lesions is detected, it is recommended to perform endoscopic surveillance with different intervals between explorations. Although the reduction in CRC incidence, endoscopic surveillance is producing a considerable increase in the number of colonoscopies. However, participation in CRC screening programs based on the fecal immunochemical test (FIT) could be a non inferior alternative to endoscopic surveillance.

Based on this hypothesis, the research group have designed a randomized clinical trial within the population CRC screening programs to compare FIT surveillance to endoscopic surveillance in patients with advanced lesions resected.

Description:

Colorectal cancer (CRC) is one of the most common malignancies in western countries. CRC screening programs have been implemented in order to reduce the burden of the disease. Screening programs in Spain are based on the biennial detection of fecal hemoglobin with a fecal immunochemical test (FIT) and a diagnostic colonoscopy if positive. The detection of at least one advanced adenoma or serrated lesion defines a high risk situation for metachronous CRC. This group of patients is recommended to perform endoscopic surveillance with different intervals between explorations. Endoscopic surveillance reduces mortality only 1.7% and increases the number of colonoscopies by 62% with an additional cost of € 68,000 for an increase of 0.9 years of life. Moreover, colonoscopy is a procedure associated with potentially serious side effects.

A recently British study shows that with a cut-off of 10 µg/g, FIT has a higher sensitivity and specificity for CRC with a significant cost reduction compared to colonoscopy surveillance. Additionally, most of the population prefers non-invasive faecal tests rather than colonoscopy.

Based on this evidence, the research group have designed a multicenter, randomized clinical trial to compare the 10 year CRC incidence after resection of advanced colonic lesions detected within CRC screening programs between endoscopic surveillance and participation in CRC screening programs based on FIT.

Apart from this purpose, the investigators will also assess the values and preferences regarding surveillance and risk of CRC. Further, the research group will evaluate the relationship between Mediterranean diet and physical activity with the detection of advanced adenomas and CRC.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 3788
• Est. completion date: June 2035
• Est. primary completion date: June 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Individuals aged 50 to 65 years.

2. Individuals with at least one advanced adenoma (tubulovillous or villous histology, high grade dysplasia or = 10mm), and / or at least three non-advanced adenomas detected and resected completely within the population-based CRC screening program.

Exclusion Criteria:

1. Personal history of CRC.

2. Colonic lesion =10mm resected without histological diagnosis.

3. More than 10 adenomas in baseline colonoscopy.

4. Serrated polyposis syndrome.

5. Two or more first-degree relatives with CRC.

6. Hereditary predisposition to CRC.

7. Relevant comorbidity with life expectancy inferior to 5 years.

8. Colonoscopy with incomplete mucosal examination.

9. Incomplete resection of baseline lesions.

10. Non-acceptance after reading the informed consent.

Related Conditions & MeSH terms

• Adenoma
• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Diagnostic Test:
• Annual FIT
Patients will be offered an annual FIT and colonoscopy will be performed if fecal hemoglobin concentration is =10µg / g of feces. After performing a colonoscopy the FIT will be sent to the patient: After one year if the unscheduled colonoscopy has been incomplete or a lesion requiring endoscopic surveillance has been completely resected. After five years if the colonoscopy has evaluated the entire mucosa, it is normal or with lesions that do not require endoscopic surveillance (1-2 non-advanced adenomas).

Procedure:
• Endoscopic surveillance.
First surveillance colonoscopy will be performed in three-year time. If an advanced adenoma or at least three non-advanced adenomas are detected, colonoscopy will be repeated after 3 years. In contrast, if colonoscopy is normal or 1-2 non-advanced adenomas are detected, colonoscopy will be repeated after 5 years.

Locations

Country	Name	City	State
Spain	Complexo Hospitalario Universitario de Ourense	Ourense

Sponsors (1)

Lead Sponsor	Collaborator
Fundacin Biomedica Galicia Sur

Country where clinical trial is conducted

Spain, 

References & Publications (16)

Atkin W, Cross AJ, Kralj-Hans I, MacRae E, Piggott C, Pearson S, Wooldrage K, Brown J, Lucas F, Prendergast A, Marchevsky N, Patel B, Pack K, Howe R, Skrobanski H, Kerrison R, Swart N, Snowball J, Duffy SW, Morris S, von Wagner C, Halloran S. Faecal immunochemical tests versus colonoscopy for post-polypectomy surveillance: an accuracy, acceptability and economic study. Health Technol Assess. 2019 Jan;23(1):1-84. doi: 10.3310/hta23010. — View Citation

Atkin WS, Valori R, Kuipers EJ, Hoff G, Senore C, Segnan N, Jover R, Schmiegel W, Lambert R, Pox C; International Agency for Research on Cancer. European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition--Colonoscopic surveillance following adenoma removal. Endoscopy. 2012 Sep;44 Suppl 3:SE151-63. doi: 10.1055/s-0032-1309821. Epub 2012 Sep 25. — View Citation

Bonello B, Ghanouni A, Bowyer HL, MacRae E, Atkin W, Halloran SP, Wardle J, von Wagner C. Using a hypothetical scenario to assess public preferences for colorectal surveillance following screening-detected, intermediate-risk adenomas: annual home-based stool test vs. triennial colonoscopy. BMC Gastroenterol. 2016 Sep 13;16(1):113. doi: 10.1186/s12876-016-0517-1. — View Citation

Bretthauer M, Loberg M, Kalager M. Long-term colorectal-cancer mortality after adenoma removal. N Engl J Med. 2014 Nov 20;371(21):2036-7. doi: 10.1056/NEJMc1411954. No abstract available. — View Citation

Craig CL, Marshall AL, Sjostrom M, Bauman AE, Booth ML, Ainsworth BE, Pratt M, Ekelund U, Yngve A, Sallis JF, Oja P. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003 Aug;35(8):1381-95. doi: 10.1249/01.MSS.0000078924.61453.FB. — View Citation

Cubiella J, Carballo F, Portillo I, Cruzado Quevedo J, Salas D, Binefa G, Mila N, Hernandez C, Andreu M, Teran A, Arana-Arri E, Ono A, Valverde MJ, Bujanda L, Hernandez V, Morillas JD, Jover R, Castells A. Incidence of advanced neoplasia during surveillance in high- and intermediate-risk groups of the European colorectal cancer screening guidelines. Endoscopy. 2016 Nov;48(11):995-1002. doi: 10.1055/s-0042-112571. Epub 2016 Aug 2. — View Citation

Greuter MJE, de Klerk CM, Meijer GA, Dekker E, Coupe VMH. Screening for Colorectal Cancer With Fecal Immunochemical Testing With and Without Postpolypectomy Surveillance Colonoscopy: A Cost-Effectiveness Analysis. Ann Intern Med. 2017 Oct 17;167(8):544-554. doi: 10.7326/M16-2891. Epub 2017 Oct 3. — View Citation

Hassan C, Quintero E, Dumonceau JM, Regula J, Brandao C, Chaussade S, Dekker E, Dinis-Ribeiro M, Ferlitsch M, Gimeno-Garcia A, Hazewinkel Y, Jover R, Kalager M, Loberg M, Pox C, Rembacken B, Lieberman D; European Society of Gastrointestinal Endoscopy. Post-polypectomy colonoscopy surveillance: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2013 Oct;45(10):842-51. doi: 10.1055/s-0033-1344548. Epub 2013 Sep 12. — View Citation

Holleczek B, Rossi S, Domenic A, Innos K, Minicozzi P, Francisci S, Hackl M, Eisemann N, Brenner H; EUROCARE-5 Working Group:. On-going improvement and persistent differences in the survival for patients with colon and rectum cancer across Europe 1999-2007 - Results from the EUROCARE-5 study. Eur J Cancer. 2015 Oct;51(15):2158-2168. doi: 10.1016/j.ejca.2015.07.024. Epub 2015 Sep 26. — View Citation

Lieberman DA, Holub J, Eisen G, Kraemer D, Morris CD. Utilization of colonoscopy in the United States: results from a national consortium. Gastrointest Endosc. 2005 Dec;62(6):875-83. doi: 10.1016/j.gie.2005.06.037. — View Citation

Mangas-Sanjuan C, Jover R, Cubiella J, Marzo-Castillejo M, Balaguer F, Bessa X, Bujanda L, Bustamante M, Castells A, Diaz-Tasende J, Diez-Redondo P, Herraiz M, Mascort-Roca JJ, Pellise M, Quintero E; Grupo de Cribado del Cancer Colorrectal de la Sociedad Espanola de Epidemiologia. Endoscopic surveillance after colonic polyps and colorrectal cancer resection. 2018 update. Gastroenterol Hepatol. 2019 Mar;42(3):188-201. doi: 10.1016/j.gastrohep.2018.11.001. Epub 2019 Jan 6. English, Spanish. — View Citation

Martinez ME, Baron JA, Lieberman DA, Schatzkin A, Lanza E, Winawer SJ, Zauber AG, Jiang R, Ahnen DJ, Bond JH, Church TR, Robertson DJ, Smith-Warner SA, Jacobs ET, Alberts DS, Greenberg ER. A pooled analysis of advanced colorectal neoplasia diagnoses after colonoscopic polypectomy. Gastroenterology. 2009 Mar;136(3):832-41. doi: 10.1053/j.gastro.2008.12.007. Epub 2008 Dec 9. — View Citation

Marzo-Castillejo M, Almeda J, Mascort JJ, Cunillera O, Saladich R, Nieto R, Pineiro P, Llagostera M, Cantero F, Segarra M, Puente D. Appropriateness of colonoscopy requests according to EPAGE-II in the Spanish region of Catalonia. BMC Fam Pract. 2015 Oct 26;16:154. doi: 10.1186/s12875-015-0369-8. — View Citation

Sotos-Prieto M, Moreno-Franco B, Ordovas JM, Leon M, Casasnovas JA, Penalvo JL. Design and development of an instrument to measure overall lifestyle habits for epidemiological research: the Mediterranean Lifestyle (MEDLIFE) index. Public Health Nutr. 2015 Apr;18(6):959-67. doi: 10.1017/S1368980014001360. Epub 2014 Jul 15. — View Citation

Zauber AG, Winawer SJ, O'Brien MJ, Lansdorp-Vogelaar I, van Ballegooijen M, Hankey BF, Shi W, Bond JH, Schapiro M, Panish JF, Stewart ET, Waye JD. Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths. N Engl J Med. 2012 Feb 23;366(8):687-96. doi: 10.1056/NEJMoa1100370. — View Citation

Zorzi M, Senore C, Turrin A, Mantellini P, Visioli CB, Naldoni C, Sassoli De' Bianchi P, Fedato C, Anghinoni E, Zappa M, Hassan C; Italian colorectal cancer screening survey group. Appropriateness of endoscopic surveillance recommendations in organised colorectal cancer screening programmes based on the faecal immunochemical test. Gut. 2016 Nov;65(11):1822-1828. doi: 10.1136/gutjnl-2015-310139. Epub 2015 Aug 21. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of invasive CRC	It is the main outcome of the study. Invasive CRC is defined as colonic adenocarcinoma that invades the submucosa. Adenocarcinomas in situ and intramucosal carcinomas will not be considered as invasive CRC.	10 years
Primary	Rate of interval CRC	Interval CRC is defined as the CRC detected between two organized surveillance (FIT or colonoscopy).	10 years
Primary	Mortality	The deaths and their cause will be collected: associated with CRC, associated with adverse effects of screening or unrelated.	10 years
Primary	Rate of advanced colonic lesions	Advanced colonic lesions will be defined as advanced adenomas (at least 10mm, hairy histology or high grade dysplasia) or advanced serrated lesions (at least 10mm or with dysplasia).	10 years
Primary	Frequency of participation in the surveillance strategy	According to the methodology of the information systems of the screening programs, three categories will be defined: non-participation, irregular participation, regular participation.	10 years
Primary	Adverse effects	Adverse effects associated with surveillance are defined as complications that require hospitalization. Those related to the surgical treatment of benign colonic lesions will be included as adverse effects.	10 years
Secondary	CRC, adenoma and advanced serrated lesions at three years	Detection of CRC, adenoma and advanced serrated lesion will be collected at 3 years of follow-up.	3 years
Secondary	Physical activity	We will use the International Physical Activity. Questionnaire (IPAQ) to mesure physical activity.	3 years
Secondary	Mediterranean lifestyle	We will use the Mediterranean Lifestyle index (MEDLIFE) to measure overall adherence to the Mediterranean lifestyle.	3 years
Secondary	Preferences of the subjects	We will use a survey with vignette questions to evaluate the values and preferences of the subjects regarding surveillance.	2 years

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