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

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

Sponsors

Lead Sponsor: VA Office of Research and Development

Source VA Office of Research and Development
Brief 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.

Overall Status Active, not recruiting
Start Date April 30, 2012
Completion Date September 29, 2028
Primary Completion Date September 29, 2028
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
The primary outcome is colorectal cancer mortality. 10 years
Secondary Outcome
Measure Time Frame
FIT Positive - If Colonoscopy is Warranted 10 Years
Enrollment 50126
Condition
Intervention

Intervention Type: Procedure

Intervention Name: Colonoscopy

Description: One time screening Colonoscopy to screen for colorectal cancer

Arm Group Label: Arm 1

Intervention Type: Procedure

Intervention Name: FIT

Description: Annual FIT testing

Arm Group Label: Arm 2

Eligibility

Criteria:

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)

Gender: All

Minimum Age: 50 Years

Maximum Age: 75 Years

Healthy Volunteers: Accepts Healthy Volunteers

Overall Official
Location
Facility:
Phoenix VA Health Care System, Phoenix, AZ | Phoenix, Arizona, 85012, United States
Central Arkansas VHS John L. McClellan Memorial Veterans Hospital, Little Rock, AR | Little Rock, Arkansas, 72205-5484, United States
VA Central California Health Care System, Fresno, CA | Fresno, California, 93703, United States
VA Loma Linda Healthcare System, Loma Linda, CA | Loma Linda, California, 92357, United States
VA Long Beach Healthcare System, Long Beach, CA | Long Beach, California, 90822, United States
VA San Diego Healthcare System, San Diego, CA | San Diego, California, 92161, United States
VA Greater Los Angeles Healthcare System, West Los Angeles, CA | West Los Angeles, California, 90073, United States
VA Eastern Colorado Health Care System, Denver, CO | Denver, Colorado, 80220, United States
VA Connecticut Healthcare System West Haven Campus, West Haven, CT | West Haven, Connecticut, 06516, United States
Washington DC VA Medical Center, Washington, DC | Washington, District of Columbia, 20422, United States
North Florida/South Georgia Veterans Health System, Gainesville, FL | Gainesville, Florida, 32608, United States
Miami VA Healthcare System, Miami, FL | Miami, Florida, 33125, United States
Orlando VA Medical Center, Orlando, FL | Orlando, Florida, 32803, United States
James A. Haley Veterans' Hospital, Tampa, FL | Tampa, Florida, 33612, United States
Atlanta VA Medical and Rehab Center, Decatur, GA | Decatur, Georgia, 30033, United States
VA Pacific Islands Health Care System, Honolulu, HI | Honolulu, Hawaii, 96819-1522, United States
Jesse Brown VA Medical Center, Chicago, IL | Chicago, Illinois, 60612, United States
Richard L. Roudebush VA Medical Center, Indianapolis, IN | Indianapolis, Indiana, 46202-2884, United States
Robley Rex VA Medical Center, Louisville, KY | Louisville, Kentucky, 40206, United States
Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD | Baltimore, Maryland, 21201, United States
VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA | Boston, Massachusetts, 02130, United States
VA Ann Arbor Healthcare System, Ann Arbor, MI | Ann Arbor, Michigan, 48105, United States
John D. Dingell VA Medical Center, Detroit, MI | Detroit, Michigan, 48201, United States
Minneapolis VA Health Care System, Minneapolis, MN | Minneapolis, Minnesota, 55417, United States
Kansas City VA Medical Center, Kansas City, MO | Kansas City, Missouri, 64128, United States
St. Louis VA Medical Center John Cochran Division, St. Louis, MO | Saint Louis, Missouri, 63106, United States
Manchester VA Medical Center, Manchester, NH | Manchester, New Hampshire, 03104, United States
East Orange Campus of the VA New Jersey Health Care System, East Orange, NJ | East Orange, New Jersey, 07018, United States
Northport VA Medical Center, Northport, NY | Northport, New York, 11768, United States
Durham VA Medical Center, Durham, NC | Durham, North Carolina, 27705, United States
Salisbury W.G. (Bill) Hefner VA Medical Center, Salisbury, NC | Salisbury, North Carolina, 28144, United States
Louis Stokes VA Medical Center, Cleveland, OH | Cleveland, Ohio, 44106, United States
Oklahoma City VA Medical Center, Oklahoma City, OK | Oklahoma City, Oklahoma, 73104, United States
VA Portland Health Care System, Portland, OR | Portland, Oregon, 97239, United States
Philadelphia MultiService Center, Philadelphia, PA | Philadelphia, Pennsylvania, 19106, United States
Providence VA Medical Center, Providence, RI | Providence, Rhode Island, 02908, United States
Memphis VA Medical Center, Memphis, TN | Memphis, Tennessee, 38104, United States
VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX | Dallas, Texas, 75216, United States
Michael E. DeBakey VA Medical Center, Houston, TX | Houston, Texas, 77030, United States
VA Salt Lake City Health Care System, Salt Lake City, UT | Salt Lake City, Utah, 84148, United States
White River Junction VA Medical Center and Regional Office, White River Junction, VT | White River Junction, Vermont, 05009-0001, United States
Hunter Holmes McGuire VA Medical Center, Richmond, VA | Richmond, Virginia, 23249, United States
VA Puget Sound Health Care System Seattle Division, Seattle, WA | Seattle, Washington, 98108, United States
Clarksburg Louis A. Johnson VA Medical Center, Clarksburg, WV | Clarksburg, West Virginia, 26301, United States
William S. Middleton Memorial Veterans Hospital, Madison, WI | Madison, Wisconsin, 53705, United States
VA Caribbean Healthcare System, San Juan, PR | San Juan, 00921, Puerto Rico
Location Countries

Puerto Rico

United States

Verification Date

April 2020

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Arm 1

Type: Other

Description: Colonoscopy (one time screening)

Label: Arm 2

Type: Other

Description: FIT (annually)

Acronym CONFIRM
Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Diagnostic

Masking: None (Open Label)

Source: ClinicalTrials.gov