Five or Ten Year Colonoscopy for 1-2 Non-Advanced Adenomatous Polyps

Adenocarcinoma of the Rectum Clinical Trial

— FORTE  

Official title:

Five or Ten Year Colonoscopy for 1-2 Non-Advanced Adenomatous Polyps

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05080673
• Other study ID #: NRG-CC005
• Secondary ID: NCI-2020-00733
• Status: Recruiting
• Phase: N/A
• Start date: October 6, 2021
• Est. completion date: November 1, 2065

Study information

• Verified date: April 2024
• Source: NRG Oncology
• Contact: Director, Department of Regulatory Affairs
• Phone: 412-339-5300
• Email: langerj[@]nrgoncology.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial examines colorectal cancer incidence in participants with 1 to 2 non-advanced adenomas randomized to surveillance colonoscopy at 10 years compared to participants randomized to surveillance colonoscopy at 5 and 10 years.

Description:

Colorectal cancer (CRC) is the fourth most common cancer and the second leading cause of cancer death among men and women in the United States (US). The lifetime risk of colorectal cancer in both men and women in the US is approximately 6%. About 93% of colorectal cancer (CRC) diagnoses are in patients older than 50 years (Siegel 2014). Randomized controlled trials show that screening for CRC significantly decreases CRC incidence and mortality (Schoen 2012, Atkin 2010, Mandel 1999, Mandel 2000). CRC screening has received a Grade A recommendation from the US Preventive Services Task Force.

In the U.S., colonoscopy is the most utilized screening modality for CRC. On a population basis, screening rates, which were around 40-50%, have now increased to 65%, and a goal to increase to 80% compliance is being promoted (CDC 2011, CDC 2013, Meester 2015).

Adenomatous polyps are the acknowledged precursors of colorectal cancer. Identification and removal of adenomas is the mechanism by which screening is effective in reducing CRC incidence and subsequent mortality. "Advanced" adenomas are adenomas which are greater than or equal to 1 cm, or have a "villous" component (tubulovillous or villous), or have foci of high grade dysplasia. Advanced adenomas are associated with increased long-term risk of cancer, even years after colonoscopy (Click 2018). The prevalence of advanced adenomas at screening colonoscopy is 5-10% (Ferlitsch 2011, Imperiale 2014). Non-advanced adenomas are adenomas greater than 1 cm with neither villous components nor high grade dysplasia. Non-advanced adenomas are much more common than advanced adenomas, present in around 30% of colonoscopy exams (Ferlitsch 2011, Imperiale 2014).

After detection of adenomas, patients are advised to return periodically for surveillance colonoscopy. Patients with 1-2 non-advanced adenomas are recommended by guidelines to return in 5 - 10 years for follow-up surveillance colonoscopy (Lieberman 2012). However, there are no guidelines on how to triage individuals to 5 as opposed to 10 years. Furthermore, there is limited evidence supporting the effectiveness of surveillance colonoscopy in reducing CRC incidence. A retrospective study in patients with advanced adenomas demonstrated benefit (Atkin 2017), but the study was not randomized and did not include patients with 1-2 non-advanced adenomas. The only randomized trial of surveillance colonoscopy was reported in the early 1990's, when participants were randomized to 3 vs. 1- and 3- year surveillance (Winawer 1993). No difference in advanced adenoma detection was observed when comparing participants examined at the two screening intervals, and as a result, guidelines were modified with participants advised to return every 3 years after adenomatous polyp detection. The recommended interval for non-advanced adenomas was gradually lengthened to the current standard, but there is no randomized, controlled data to support that interval. Furthermore, observational data of surveillance colonoscopy practice in the U.S. demonstrate that recommended intervals are often not adhered to, and individuals return for repeat testing well ahead of guideline recommendations (Schoen 2010, Lieberman 2014).

Furthermore, if anything, retrospective, natural history studies of non-advanced adenomas do not support the association of non-advanced adenoma with a higher risk of subsequent colorectal cancer (Atkin 1992, Spencer 1984, Loberg 2014). For example, in a classic study from the United Kingdom, patients with small rectosigmoid adenomas, even if multiple, did not have an increased risk of CRC compared to the general population, over a 14-year mean follow-up time (Atkin 1992). In a recent observational study from Norway, participants with a low-risk adenoma followed over a median of 7.7 years (maximum 19 years) without subsequent surveillance colonoscopy, had a lower CRC mortality than the general population (Loberg 2014), implying that although the initial colonoscopy may be protective, subsequent follow-up colonoscopy was not required. More recently, several studies have reported that individuals with non-advanced adenomas do not have an increased risk of colorectal cancer compared to those with no adenomas (Click 2018, Lieberman 2019, Lee 2019).

Another recent major development affecting screening is that practitioners of colonoscopy are now recommended to monitor and insure their adenoma detection rates are high. Data from Poland (Kaminski 2010) and Kaiser Permanente in California (Corley 2014) have demonstrated that a higher adenoma detection rate (ADR) is associated with a lower long-term risk of interval CRC, or cancer occurring after colonoscopy. Our understanding of these observations is premised on the notion that leaving pre-neoplastic tissue (adenomas) in situ, (such as what occurs with a lower ADR), increases the chance that an adenoma left behind will subsequently transform into cancer. The concern over interval cancers has stimulated quality concerns about the practice of colonoscopy. Guidelines for a recommended ADR at screening colonoscopy are rising, from the initial targets of 15% in women and 25% in men (Lieberman 2012) to 20% in women and 30% in men or 25% overall. ADRs in clinical studies are now commonly over 30% and some practitioners report rates exceeding 50%. However, adenomas that are detected when the ADR is high or as it increases over time are generally small, non-advanced adenomas.

Current clinical practice favoring colonoscopy-based screening with increased emphasis on detection of adenomas, most of which will turn out to be small, non-advanced adenomas, will greatly increase demand for utilization of surveillance colonoscopy exams in the coming decades. Yet, the evidence for determining the benefit, optimal timing, and recommended frequency of surveillance colonoscopy is unknown. A randomized, clinical trial to demonstrate the difference in yield between 5- or 10-year surveillance for participants with non-advanced adenoma is needed to guide clinical practice. Only a randomized trial will be authoritative enough to define good clinical practice and directly influence clinical care.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 9500
• Est. completion date: November 1, 2065
• Est. primary completion date: November 1, 2035
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 70 Years

Eligibility

Inclusion Criteria:

• • The participant must have signed and dated an IRB-approved consent form that conforms to federal and institutional guidelines.

• Participants with a first-time diagnosis of 1-2 non-advanced tubular adenomas (less than 10 mm without tubulovillous or villous changes or high grade or severe dysplasia) from the qualifying colonoscopy within 4 years prior to randomization.

• Sessile serrated polyps/adenomas, as long as they do not meet the criteria for advanced adenomas, will be considered as non-advanced adenomas.

• Qualifying colonoscopy must be a complete colonoscopy with visualization of the cecum and with adequate cleansing within 4 years prior to randomization.

• Complete excision of all observed polyps in qualifying colonoscopy

• Participants must be able to read or understand English or Spanish.

Exclusion Criteria:

• • Prior history of colorectal cancer or colorectal adenomas including sessile serrated polyps/adenomas excluding those found on the qualifying colonoscopy.

• Prior history of a hyperplastic polyp measuring greater than or equal to 1 cm in size.

• Traditional serrated adenomas found on the qualifying colonoscopy.

• Hyperplastic polyp measuring greater than or equal to 1 cm in size found on the qualifying colonoscopy.

• Previous malignancies unless the patient has been disease-free for 5 or more years prior to randomization and is deemed by the physician to be at low risk for recurrence. Patients with the following cancers are eligible if diagnosed and treated within the past 5 years: all in situ cancers and basal cell and squamous cell carcinoma of the skin.

• Colonoscopy performed after the qualifying colonoscopy but prior to randomization.

• Incomplete qualifying colonoscopy (e.g., cecum not visualized).

• Incomplete endoscopic excision of adenomatous polyps based on colonoscopist impression at qualifying colonoscopy. (Excision of all hyperplastic rectosigmoid polyps is not required.)

• Sub-total colectomy or total proctocolectomy. (Segmental resections are allowed.)

• Family history of CRC diagnosed at greater than or equal to 60 years of age in a first degree relative (mother, father, child, sibling) or in two first degree relatives with CRC at any age.

• Participants with a clinical diagnosis of a significant heritable risk for colorectal cancer (Familial Adenomatous Polyposis, Hereditary Nonpolyposis Colorectal Cancer [Lynch Syndrome]).

• Participants tested positive for a Familial Adenomatous Polyposis, Hereditary Nonpolyposis Colorectal Cancer [Lynch Syndrome] genetic mutation that increases risk of colorectal cancer.

• Inflammatory bowel disease (e.g., Crohn's Disease, ulcerative colitis).

• Life expectancy less than 10 years due to comorbid conditions in the opinion of the investigator.

• Other comorbid conditions that would prevent the participant from having colonoscopies or would prevent required follow-up.

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Colon
• Adenocarcinoma of the Rectum
• Adenomatous Polyps

Intervention

Procedure:
• 5-year and 10 Year Surveillance Colonoscopy after Qualifying Colonoscopy
The five- and ten-year colonoscopies, in addition to any unscheduled colonoscopies, will be performed according to currently accepted guidelines for the performance of quality colonoscopy. Participants will be given the standardized colonoscopy preparation instructions per institutional standards.

Locations

Country	Name	City	State
United States	Riverwood Healthcare Center	Aitkin	Minnesota
United States	Ascension Saint Elizabeth Hospital	Appleton	Wisconsin
United States	Mission Hope Medical Oncology - Arroyo Grande	Arroyo Grande	California
United States	Duluth Clinic Ashland	Ashland	Wisconsin
United States	Northwest Wisconsin Cancer Center	Ashland	Wisconsin
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	Flaget Memorial Hospital	Bardstown	Kentucky
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Essentia Health Saint Joseph's Medical Center	Brainerd	Minnesota
United States	Harrison Medical Center	Bremerton	Washington
United States	Ascension Southeast Wisconsin Hospital - Elmbrook Campus	Brookfield	Wisconsin
United States	Saint Joseph Regional Cancer Center	Bryan	Texas
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Minnesota Oncology - Burnsville	Burnsville	Minnesota
United States	Cambridge Medical Center	Cambridge	Minnesota
United States	Ralph H Johnson VA Medical Center	Charleston	South Carolina
United States	John H Stroger Jr Hospital of Cook County	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	Ascension Calumet Hospital	Chilton	Wisconsin
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Anderson	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Westside	Cincinnati	Ohio
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado
United States	Saint Francis Cancer Center	Colorado Springs	Colorado
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Commonwealth Cancer Center-Corbin	Corbin	Kentucky
United States	Alegent Health Mercy Hospital	Council Bluffs	Iowa
United States	Greater Regional Medical Center	Creston	Iowa
United States	Carle on Vermilion	Danville	Illinois
United States	Essentia Health - Deer River Clinic	Deer River	Minnesota
United States	Porter Adventist Hospital	Denver	Colorado
United States	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Essentia Health Saint Mary's - Detroit Lakes Clinic	Detroit Lakes	Minnesota
United States	Epic Care-Dublin	Dublin	California
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota
United States	Miller-Dwan Hospital	Duluth	Minnesota
United States	Mercy Medical Center	Durango	Colorado
United States	Southwest Oncology PC	Durango	Colorado
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Bay Area Breast Surgeons Inc	Emeryville	California
United States	Epic Care Partners in Cancer Care	Emeryville	California
United States	Saint Elizabeth Hospital	Enumclaw	Washington
United States	Essentia Health Cancer Center-South University Clinic	Fargo	North Dakota
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Medical Center Fargo	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Sanford South University Medical Center	Fargo	North Dakota
United States	Southpointe-Sanford Medical Center Fargo	Fargo	North Dakota
United States	Saint Francis Hospital	Federal Way	Washington
United States	Lake Region Healthcare Corporation-Cancer Care	Fergus Falls	Minnesota
United States	Essentia Health - Fosston	Fosston	Minnesota
United States	Ascension Saint Francis - Reiman Cancer Center	Franklin	Wisconsin
United States	Ascension Southeast Wisconsin Hospital - Franklin	Franklin	Wisconsin
United States	Unity Hospital	Fridley	Minnesota
United States	CHI Health Saint Francis	Grand Island	Nebraska
United States	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan
United States	Mercy Health Saint Mary's	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina
United States	Essentia Health-Hayward Clinic	Hayward	Wisconsin
United States	Essentia Health Hibbing Clinic	Hibbing	Minnesota
United States	CHI Saint Vincent Cancer Center Hot Springs	Hot Springs	Arkansas
United States	Essentia Health - Jamestown Clinic	Jamestown	North Dakota
United States	Ascension Borgess Cancer Center	Kalamazoo	Michigan
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Saint Clare Hospital	Lakewood	Washington
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky
United States	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Saint Joseph London	London	Kentucky
United States	Longmont United Hospital	Longmont	Colorado
United States	Rocky Mountain Cancer Centers-Longmont	Longmont	Colorado
United States	UCLA / Jonsson Comprehensive Cancer Center	Los Angeles	California
United States	Jewish Hospital	Louisville	Kentucky
United States	Saints Mary and Elizabeth Hospital	Louisville	Kentucky
United States	UofL Health Medical Center Northeast	Louisville	Kentucky
United States	Fairview Clinics and Surgery Center Maple Grove	Maple Grove	Minnesota
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Contra Costa Regional Medical Center	Martinez	California
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Ascension Columbia Saint Mary's Hospital Ozaukee	Mequon	Wisconsin
United States	Ascension Columbia Saint Mary's Hospital - Milwaukee	Milwaukee	Wisconsin
United States	Ascension Saint Francis Hospital	Milwaukee	Wisconsin
United States	Ascension Southeast Wisconsin Hospital - Saint Joseph Campus	Milwaukee	Wisconsin
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Health Partners Inc	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Monticello Cancer Center	Monticello	Minnesota
United States	Morristown Medical Center	Morristown	New Jersey
United States	Mercy Health Mercy Campus	Muskegon	Michigan
United States	Cancer Center of Western Wisconsin	New Richmond	Wisconsin
United States	New Ulm Medical Center	New Ulm	Minnesota
United States	Lakeland Hospital Niles	Niles	Michigan
United States	Cancer and Hematology Centers of Western Michigan - Norton Shores	Norton Shores	Michigan
United States	Alta Bates Summit Medical Center - Summit Campus	Oakland	California
United States	Bay Area Tumor Institute	Oakland	California
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Immanuel Medical Center	Omaha	Nebraska
United States	Alegent Health Lakeside Hospital	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Ascension Mercy Hospital	Oshkosh	Wisconsin
United States	Midlands Community Hospital	Papillion	Nebraska
United States	Essentia Health - Park Rapids	Park Rapids	Minnesota
United States	Parker Adventist Hospital	Parker	Colorado
United States	Cancer Center at Saint Joseph's	Phoenix	Arizona
United States	UPMC-Presbyterian Hospital	Pittsburgh	Pennsylvania
United States	Fairview Northland Medical Center	Princeton	Minnesota
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Ascension All Saints Hospital	Racine	Wisconsin
United States	Spectrum Health Reed City Hospital	Reed City	Michigan
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan
United States	Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Pacific Central Coast Health Center-San Luis Obispo	San Luis Obispo	California
United States	Essentia Health Sandstone	Sandstone	Minnesota
United States	Mission Hope Medical Oncology - Santa Maria	Santa Maria	California
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Jewish Hospital Medical Center South	Shepherdsville	Kentucky
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Essentia Health-Spooner Clinic	Spooner	Wisconsin
United States	Marshfield Clinic Stevens Point Center	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Essentia Health Saint Mary's Hospital - Superior	Superior	Wisconsin
United States	Franciscan Research Center-Northwest Medical Plaza	Tacoma	Washington
United States	Sanford Thief River Falls Medical Center	Thief River Falls	Minnesota
United States	Munson Medical Center	Traverse City	Michigan
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	Kaiser Permanente-Vallejo	Vallejo	California
United States	Essentia Health Virginia Clinic	Virginia	Minnesota
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Epic Care Cyberknife Center	Walnut Creek	California
United States	Ascension Medical Group Southeast Wisconsin - Mayfair Road	Wauwatosa	Wisconsin
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Sanford Cancer Center Worthington	Worthington	Minnesota
United States	Fairview Lakes Medical Center	Wyoming	Minnesota
United States	Metro Health Hospital	Wyoming	Michigan
United States	Rush-Copley Healthcare Center	Yorkville	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
NRG Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of advanced adenoma	To examine advanced adenoma incidence in participants with 1 to 2 non-advanced adenomas randomized to surveillance colonoscopy at 10 years compared to participants randomized to surveillance colonoscopy at 5 and 10 years.	10 years
Other	Colorectal cancer mortality	To examine colorectal cancer mortality in participants with 1 to 2 non-advanced adenomas randomized to surveillance colonoscopy at 10 years compared to participants randomized to surveillance colonoscopy at 5 and 10 years.	10 years
Other	Incidence of stage III-IV colorectal cancer	To examine stage III-IV colorectal cancer incidence in participants with 1 to 2 non-advanced adenomas randomized to surveillance colonoscopy at 10 years compared to participants randomized to surveillance colonoscopy at 5 and 10 years.	10 years
Primary	Incidence of colorectal cancer	To examine colorectal cancer incidence in participants with 1 to 2 non-advanced adenomas randomized to surveillance colonoscopy at 10 years compared to participants randomized to surveillance colonoscopy at 5 and 10 years.	10 years