Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM)

Colorectal Cancer Clinical Trial

— CONFIRM  

Official title:

CSP #577 - Colonoscopy vs. Fecal Immunochemical Testing in Reducing Mortality From Colorectal Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01239082
• Other study ID #: 577
• Status: Active, not recruiting
• Phase: N/A
• Start date: April 30, 2012
• Est. completion date: December 1, 2028

Study information

• Verified date: February 2024
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Colorectal cancer (CRC) is currently the second most common cause of cancer death in the United States, and one of the most preventable cancers. It has been shown in several randomized controlled trials that screening using fecal occult blood testing (FOBT) reduces CRC mortality by 13-33%. While there is strong consensus amongst experts regarding the value of CRC screening, the best approach to screening is not clear. Of the widely recommended modalities, FOBT and colonoscopy are the most commonly used within the United States. FOBT is inexpensive, non-invasive, and its use as a screening tool is supported by the highest quality evidence (i.e. randomized controlled trials). Moreover, newer FOBT, such as fecal immunochemical tests or FITs, have advantages over conventional FOBT in terms of both test characteristics and ease of use that make them quite attractive as a population-based screening tool.

While colonoscopy is invasive and has higher up-front risks and costs than FOBT, it does afford the opportunity to directly assess the colonic mucosa and is widely believed to be the best test to detect colorectal cancer. In addition, colonoscopy allows for the detection and removal of colorectal adenomas -a well recognized colorectal cancer precursor. There is indirect evidence that suggests colonoscopy is effective in reducing colorectal cancer mortality, but to date, no large clinical trials have been completed to support this assumption. While colonoscopy use is increasing, data is emerging that colonoscopy may not be as effective as previously believed. Prior support for colonoscopy as a screening test relied upon effectiveness estimates that now appear to be overly optimistic. Given the invasive nature of colonoscopy, the associated small, but real risk of complications, and dramatically higher costs than other screening tests, it is especially important to determine the true comparative effectiveness of colonoscopy relative to other proven non-invasive options.

The investigators propose to perform a, large, simple, multicenter, randomized, parallel group trial directly comparing screening colonoscopy with annual FIT screening in average risk individuals. The hypothesis is that colonoscopy will be superior to FIT in the prevention of colorectal cancer mortality measured over 10 years. Individuals will be enrolled if they are currently eligible for CRC screening (e.g. no colonoscopy in the past 10 years and no FOBT in the past 1 year) and are between 50 and 75 years of age. The investigators will exclude individuals for whom colonoscopy is indicated (e.g. signs or symptoms of CRC, first degree family member with CRC, personal history of colorectal neoplasia or inflammatory bowel disease).

All participants will complete baseline demographic, medication, and lifestyle questionnaires (e.g. diet, non-steroidal anti-inflammatory use, frequency of exercise) prior to randomization in a 1:1 ratio to either screening colonoscopy or annual FIT screening (Figure 1). Those testing positive by FIT will undergo evaluation to determine appropriateness for colonoscopy. Screening will be performed in a manner consistent with the currently accepted standard of care in order to determine the comparative effectiveness of the two screening strategies. Participants will be surveyed annually to determine if they have undergone colonoscopy or been diagnosed with CRC.

The primary study endpoint will be CRC mortality within 10 years of enrollment. The secondary endpoints are (1) the incidence of CRC within 10 years of enrollment and (2) major complications of colonoscopy. Mortality will be determined through queries of the VA Vital Status File. Cause of death will be determined primarily using death certificates from the National Death Index-Plus database, augmented by adjudication of medical records for known CRC cases where CRC is not listed as a cause of death on the death certificate. The investigators postulate that screening colonoscopy will result in a 40% reduction in CRC mortality over 10 years relative to annual FIT screening. Using a log-rank test with a 2-sided test of significance, =0.05, a sample size of 50,000 participants will be required to test the primary hypothesis with 82% power, assuming a 1% annual rate of crossover from FIT to colonoscopy and a 0.5% annual rate of loss to follow-up. The planned study duration is 12.5 years with 2.5 years of recruitment and 10 years of follow-up for all enrolled participants.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50126
• Est. completion date: December 1, 2028
• Est. primary completion date: December 1, 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years to 75 Years

Eligibility

Inclusion Criteria:

• Male and female adults aged 50-75 years of age

• Veteran

• Able to provide informed consent

Exclusion Criteria:

• Symptoms of lower gastrointestinal tract disease warranting colonoscopic evaluation, including:

• More than one episode of rectal bleeding within the past 6 months

• Documented iron deficiency anemia

• Significant documented unintentional weight loss (>10% of baseline weight) over 6 months

• Family history of CRC in a first degree relative at any age

• Prior history of colonic disease including:

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

• One or more colorectal neoplastic polyps (i.e. adenomas)

• Colorectal cancer

• Prior history of colonic resection

• Prior colonic examination, including:

• Colonoscopy within the past 9.5 years

• Sigmoidoscopy within the past 5 years

• Barium enema within the past 5 years

• CT colonography within the past 5 years

• gFOBT or FIT in the past 10 months

• Stool DNA test within the past 3 years

• Pregnancy

• Prisoner

• Significant comorbidity that would preclude benefit from screening or pose significant risk for the performance of colonoscopy (e.g. severe lung disease, end-stage renal disease, end-stage liver disease, severe heart failure, recent diagnosis of cancer (with the exception of non-melanoma skin cancer))

• Participation in a concurrent interventional study pertaining to the colon or rectum (including studies of colonoscopy or colorectal cancer screening. Waivers to this exclusion criteria can be requested and granted with the approval of the CONFIRM study co-chairs, the Cooperative Study Program and the leadership of the other study.

• Likely inability to track the individual over time (e.g. no permanent address at the time of screening for study entry)

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Procedure:
• Colonoscopy
One time screening Colonoscopy to screen for colorectal cancer
• FIT
Annual FIT testing

Locations

Country	Name	City	State
Puerto Rico	VA Caribbean Healthcare System, San Juan, PR	San Juan
United States	VA Ann Arbor Healthcare System, Ann Arbor, MI	Ann Arbor	Michigan
United States	Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD	Baltimore	Maryland
United States	VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA	Boston	Massachusetts
United States	Jesse Brown VA Medical Center, Chicago, IL	Chicago	Illinois
United States	Clarksburg Louis A. Johnson VA Medical Center, Clarksburg, WV	Clarksburg	West Virginia
United States	Louis Stokes VA Medical Center, Cleveland, OH	Cleveland	Ohio
United States	VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX	Dallas	Texas
United States	Atlanta VA Medical and Rehab Center, Decatur, GA	Decatur	Georgia
United States	VA Eastern Colorado Health Care System, Denver, CO	Denver	Colorado
United States	John D. Dingell VA Medical Center, Detroit, MI	Detroit	Michigan
United States	Durham VA Medical Center, Durham, NC	Durham	North Carolina
United States	East Orange Campus of the VA New Jersey Health Care System, East Orange, NJ	East Orange	New Jersey
United States	VA Central California Health Care System, Fresno, CA	Fresno	California
United States	North Florida/South Georgia Veterans Health System, Gainesville, FL	Gainesville	Florida
United States	VA Pacific Islands Health Care System, Honolulu, HI	Honolulu	Hawaii
United States	Michael E. DeBakey VA Medical Center, Houston, TX	Houston	Texas
United States	Richard L. Roudebush VA Medical Center, Indianapolis, IN	Indianapolis	Indiana
United States	Kansas City VA Medical Center, Kansas City, MO	Kansas City	Missouri
United States	Central Arkansas VHS John L. McClellan Memorial Veterans Hospital, Little Rock, AR	Little Rock	Arkansas
United States	VA Loma Linda Healthcare System, Loma Linda, CA	Loma Linda	California
United States	VA Long Beach Healthcare System, Long Beach, CA	Long Beach	California
United States	Robley Rex VA Medical Center, Louisville, KY	Louisville	Kentucky
United States	William S. Middleton Memorial Veterans Hospital, Madison, WI	Madison	Wisconsin
United States	Manchester VA Medical Center, Manchester, NH	Manchester	New Hampshire
United States	Memphis VA Medical Center, Memphis, TN	Memphis	Tennessee
United States	Miami VA Healthcare System, Miami, FL	Miami	Florida
United States	Minneapolis VA Health Care System, Minneapolis, MN	Minneapolis	Minnesota
United States	Northport VA Medical Center, Northport, NY	Northport	New York
United States	Oklahoma City VA Medical Center, Oklahoma City, OK	Oklahoma City	Oklahoma
United States	Orlando VA Medical Center, Orlando, FL	Orlando	Florida
United States	Philadelphia MultiService Center, Philadelphia, PA	Philadelphia	Pennsylvania
United States	Phoenix VA Health Care System, Phoenix, AZ	Phoenix	Arizona
United States	VA Portland Health Care System, Portland, OR	Portland	Oregon
United States	Providence VA Medical Center, Providence, RI	Providence	Rhode Island
United States	Hunter Holmes McGuire VA Medical Center, Richmond, VA	Richmond	Virginia
United States	St. Louis VA Medical Center John Cochran Division, St. Louis, MO	Saint Louis	Missouri
United States	Salisbury W.G. (Bill) Hefner VA Medical Center, Salisbury, NC	Salisbury	North Carolina
United States	VA Salt Lake City Health Care System, Salt Lake City, UT	Salt Lake City	Utah
United States	VA San Diego Healthcare System, San Diego, CA	San Diego	California
United States	VA Puget Sound Health Care System Seattle Division, Seattle, WA	Seattle	Washington
United States	James A. Haley Veterans' Hospital, Tampa, FL	Tampa	Florida
United States	Washington DC VA Medical Center, Washington, DC	Washington	District of Columbia
United States	VA Connecticut Healthcare System West Haven Campus, West Haven, CT	West Haven	Connecticut
United States	VA Greater Los Angeles Healthcare System, West Los Angeles, CA	West Los Angeles	California
United States	White River Junction VA Medical Center and Regional Office, White River Junction, VT	White River Junction	Vermont

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (3)

Imperiale TF, Ransohoff DF, Itzkowitz SH, Levin TR, Lavin P, Lidgard GP, Ahlquist DA, Berger BM. Multitarget stool DNA testing for colorectal-cancer screening. N Engl J Med. 2014 Apr 3;370(14):1287-97. doi: 10.1056/NEJMoa1311194. Epub 2014 Mar 19. — View Citation

May FP, Yano EM, Provenzale D, Neil Steers W, Washington DL. The Association Between Primary Source of Healthcare Coverage and Colorectal Cancer Screening Among US Veterans. Dig Dis Sci. 2017 Aug;62(8):1923-1932. doi: 10.1007/s10620-017-4607-x. Epub 2017 — View Citation

Robertson DJ, Dominitz JA, Beed A, Boardman KD, Del Curto BJ, Guarino PD, Imperiale TF, LaCasse A, Larson MF, Gupta S, Lieberman D, Planeta B, Shaukat A, Sultan S, Menees SB, Saini SD, Schoenfeld P, Goebel S, von Rosenvinge EC, Baffy G, Halasz I, Pedrosa — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary outcome is colorectal cancer mortality.	The primary outcome is colorectal cancer mortality. Patient survival will be monitored for 10 years, with survival assessed by both annual surveys and data reported to vital status registries, including the VA Vital Status File, which is comprised of the VA Beneficiary Identification and Records Locator System (BIRLS), the Medical SAS Inpatient Data Sets, and the Social Security Administration's Death Master File. The National Center for Health Statistics' National Death Index database will be used to find cause of death.	10 years
Secondary	FIT Positive - If Colonoscopy is Warranted	There are no physical risks associated with performance of FIT screening. However, those with a positive FIT will be referred for evaluation by their primary care provider or site principal investigator to determine if colonoscopy is warranted. Those subsequently referred for colonoscopy will be exposed to its risks, and complications will be tracked as a secondary outcome measure	10 Years