The National CT Colonography Trial (ACRIN6664)

The National CT Colonography Trial: Multicenter Assessment of Accuracy for Detection of Large Adenomas and Cancers in a Healthy Screening Population

RATIONALE: New diagnostic procedures such as computed tomographic colonography may improve the ability to detect colorectal cancer and may provide a less invasive method of detection.

PURPOSE: This clinical trial is studying how well computed tomographic colonography works in screening healthy participants for colorectal cancer.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Procedure: CT Colonography

Detailed Description

OBJECTIVES:

Primary

• Compare the sensitivity of computed tomographic colonography (CTC) vs colonoscopy for detecting significantly large lesions (≥ 10 mm in diameter) in asymptomatic participants, in terms of specificity, area under the ROC curve, and predictive values for detecting clinically significant colorectal neoplasia.

Secondary

• Determine the interobserver variation in accuracy of interpreting CTC examinations of these participants, including any benefits of a primary 3-dimensional read and/or independent second interpretations.
• Determine the effects of different colon preparations on the accuracy of CTC in these participants.
• Compare participant acceptance and willingness to have a repeat examination by CTC vs colonoscopy.
• Determine the accuracy of CTC in detecting flat lesions in the colon of these participants.

OUTLINE: This is a multicenter study.

Participants receive an oral laxative, oral bisacodyl, and three doses of oral barium sulphate 24 hours before imaging. After cathartic cleansing, participants undergo computed tomographic colonography followed by colonoscopy.

Participants are followed up for approximately 4 weeks.

PROJECTED ACCRUAL: A total of 2,607 participants will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 2600
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259-5499
      • Mayo Clinic Scottsdale
  • California
    • La Jolla, California, United States, 92093-0658
      • Moores UCSD Cancer Center
    • Los Angeles, California, United States, 90095-1781
      • Jonsson Comprehensive Cancer Center at UCLA
    • San Francisco, California, United States, 94121
      • Veterans Affairs Medical Center - San Francisco
  • Colorado
    • Englewood, Colorado, United States, 80112
      • Invision/Radiology Imaging Associates - Englewood
  • Connecticut
    • New Haven, Connecticut, United States, 06520-8028
      • Yale Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60637-1470
      • University of Chicago Cancer Research Center
    • Springfield, Illinois, United States, 62781
      • Clinical Radiologists, S.C. at Memorial Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21231-2410
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Mallinckrodt Institute of Radiology at Washington University Medical Center
  • Texas
    • Houston, Texas, United States, 77030-4009
      • M.D. Anderson Cancer Center at University of Texas
  • Virginia
    • Richmond, Virginia, United States, 23298-0037
      • Virginia Commonwealth University Massey Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

1. Inclusion Criteria

   • Male or female outpatients
   • Aged 50 years or older
   • Scheduled for screening colonoscopy
   • Participant's signed informed consent

2. Exclusion Criteria

   • Symptoms of disease of the lower gastrointestinal tract, including

     • Melanotic stools or/and hematochezia on more than one occasion in the previous six months
     • Lower abdominal pain that would normally require a medical evaluation
   • Inflammatory bowel disease and/or familial polyposis syndrome
   • Serious medical conditions that would increase the risk associated with colonoscopy or are so severe that screening would have no benefit
   • Pregnancy
   • Previous colonoscopy within the past five years
   • Anemia (hemoglobin less than 10 gm/dl)
   • Positive fecal occult blood test (FOBT)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CT Colonography; CT colonography conducted during the same assessment as colonoscopy.	Procedure: CT Colonography; CT colonography performed for comparison with colonoscopy results performed during the same screening assessment.; Other Names: colonoscopy; CT colonography trial

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Advanced Adenomas (>=10mm) as Determined by Colonoscopy (Per Patient)	Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard (RS) for determining the existence of advanced adenomas. RS+: Colonoscopy found at least 1 Advanced adenomas >=10mm (as measured at pathology) RS-: No Advanced adenomas >=10mm found by colonoscopy (as measured at pathology)	within 30 days
Number of Participants With Advanced Adenomas (>=9mm) Detected by CT Colonoscopy (Per Patient)	Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard (RS) for determining the existence of advanced adenomas. RS+: Colonoscopy found at least 1 Advanced adenomas >=9mm (as measured at pathology) RS-: No Advanced adenomas >=9mm found by colonoscopy (as measured at pathology)	within 30 days
Number of Participants With Advanced Adenomas (>=8mm) Detected by CT Colonoscopy (Per Patient)	Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard (RS) for determining the existence of advanced adenomas. RS+: Colonoscopy found at least 1 Advanced adenomas >=8mm (as measured at pathology) RS-: No Advanced adenomas >=8mm found by colonoscopy (as measured at pathology)	within 30 days
Number of Participants With Advanced Adenomas (>=7mm) Detected by CT Colonoscopy (Per Patient)	Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard (RS) for determining the existence of advanced adenomas. RS+: Colonoscopy found at least 1 Advanced adenomas >=7mm (as measured at pathology) RS-: No Advanced adenomas >=7mm found by colonoscopy (as measured at pathology)	within 30 days
Number of Participants With Advanced Adenomas (>=6mm) Detected by CT Colonoscopy (Per Patient)	Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard (RS) for determining the existence of advanced adenomas. RS+: Colonoscopy found at least 1 Advanced adenomas >=6mm (as measured at pathology) RS-: No Advanced adenomas >=16mm found by colonoscopy (as measured at pathology)	within 30 days
Number of Participants With Advanced Adenomas (>=5mm) Detected by CT Colonoscopy (Per Patient)	Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard (RS) for determining the existence of advanced adenomas. RS+: Colonoscopy found at least 1 Advanced adenomas >=5mm (as measured at pathology) RS-: No Advanced adenomas >=5mm found by colonoscopy (as measured at pathology)	within 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Advanced Adenoma or Cancer Lesions (>=10mm) Detected by CT Colonoscopy (Per Lesion)	Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard for determining the existence of advanced adenomas. CTC lesions needed to be within 2 segments and 50% size of the lesions removed via colonoscopy to be considered "detected"	within 30 days
Number of Advanced Adenoma or Cancer Lesions (>=9mm) Detected by CT Colonoscopy (Per Lesion)	Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard for determining the existence of advanced adenomas. CTC lesions needed to be within 2 segments and 50% size of the lesions removed via colonoscopy to be considered "detected"	within 30 days
Number of Advanced Adenoma or Cancer Lesions (>=8mm) Detected by CT Colonoscopy (Per Lesion)	Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard for determining the existence of advanced adenomas. CTC lesions needed to be within 2 segments and 50% size of the lesions removed via colonoscopy to be considered "detected"	within 30 days
Number of Advanced Adenoma or Cancer Lesions (>=7mm) Detected by CT Colonoscopy (Per Lesion)	Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard for determining the existence of advanced adenomas. CTC lesions needed to be within 2 segments and 50% size of the lesions removed via colonoscopy to be considered "detected"	within 30 days
Number of Advanced Adenoma or Cancer Lesions (>=6mm) Detected by CT Colonoscopy (Per Lesion)	Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard for determining the existence of advanced adenomas. CTC lesions needed to be within 2 segments and 50% size of the lesions removed via colonoscopy to be considered "detected"	within 30 days
Number of Advanced Adenoma or Cancer Lesions (>=5mm) Detected by CT Colonoscopy (Per Lesion)	Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard for determining the existence of advanced adenomas. CTC lesions needed to be within 2 segments and 50% size of the lesions removed via colonoscopy to be considered "detected"	within 30 days
Interobserver Sensitivity Variability	Evaluate interobserver variability in Sensitivity (P(T+|D+)) and 95% CI) when interpreting CTC examinations Each study was randomly assigned to be read independently using either a primary 2D search method (conventional 2D image display with 3D endoluminal problem solving), or a primary 3D search method (including the capability of displaying multiplanar 2D) and without prior knowledge of the colonoscopy results. A second trained radiologist of similar skill was assigned to read the images using the other modality Readers were then classified as high performing or not high performing	at baseline

Collaborators and Investigators

• Sponsor: American College of Radiology Imaging Network
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: C. Daniel Johnson, MD, Mayo Clinic

Publications and helpful links

General Publications

• Vanness DJ, Knudsen AB, Lansdorp-Vogelaar I, Rutter CM, Gareen IF, Herman BA, Kuntz KM, Zauber AG, van Ballegooijen M, Feuer EJ, Chen MH, Johnson CD. Comparative economic evaluation of data from the ACRIN National CT Colonography Trial with three cancer intervention and surveillance modeling network microsimulations. Radiology. 2011 Nov;261(2):487-98. doi: 10.1148/radiol.11102411. Epub 2011 Aug 3.
• Johnson CD, Herman BA, Chen MH, Toledano AY, Heiken JP, Dachman AH, Kuo MD, Menias CO, Siewert B, Cheema JI, Obregon R, Fidler JL, Zimmerman P, Horton KM, Coakley KJ, Iyer RB, Hara AK, Halvorsen RA Jr, Casola G, Yee J, Blevins M, Burgart LJ, Limburg PJ, Gatsonis CA. The National CT Colonography Trial: assessment of accuracy in participants 65 years of age and older. Radiology. 2012 May;263(2):401-8. doi: 10.1148/radiol.12102177. Epub 2012 Feb 23.
• Hara AK, Blevins M, Chen MH, Dachman AH, Kuo MD, Menias CO, Siewert B, Cheema JI, Obregon RG, Fidler JL, Zimmerman P, Horton KM, Coakley KJ, Iyer RB, Halvorsen RA Jr, Casola G, Yee J, Herman BA, Johnson CD. ACRIN CT colonography trial: does reader's preference for primary two-dimensional versus primary three-dimensional interpretation affect performance? Radiology. 2011 May;259(2):435-41. doi: 10.1148/radiol.11100250. Epub 2011 Mar 1.
• Hara AK, Kuo MD, Blevins M, Chen MH, Yee J, Dachman A, Menias CO, Siewert B, Cheema JI, Obregon RG, Fidler JL, Zimmerman P, Horton KM, Coakley K, Iyer RB, Halvorsen RA Jr, Casola G, Johnson CD. National CT colonography trial (ACRIN 6664): comparison of three full-laxative bowel preparations in more than 2500 average-risk patients. AJR Am J Roentgenol. 2011 May;196(5):1076-82. doi: 10.2214/AJR.10.4334.
• Siewert B, Gareen I, Vanness D, et al.: ACRIN 6664: patient acceptance and preferance of CT colonography compared to optical colonoscopy for colon cancer screening. [Abstract] J Clin Oncol 27 (Suppl 15): A-4034, 2009.
• Johnson CD, Chen MH, Toledano AY, Heiken JP, Dachman A, Kuo MD, Menias CO, Siewert B, Cheema JI, Obregon RG, Fidler JL, Zimmerman P, Horton KM, Coakley K, Iyer RB, Hara AK, Halvorsen RA Jr, Casola G, Yee J, Herman BA, Burgart LJ, Limburg PJ. Accuracy of CT colonography for detection of large adenomas and cancers. N Engl J Med. 2008 Sep 18;359(12):1207-17. doi: 10.1056/NEJMoa0800996. Erratum In: N Engl J Med. 2008 Dec 25;359(26):2853.

Helpful Links

• Clinical trial summary from the National Cancer Institute's PDQ® database

Study record dates

Study Major Dates

• Study Start: February 1, 2005
• Primary Completion (Actual): September 11, 2007
• Study Completion (Actual): May 13, 2010

Study Registration Dates

• First Submitted: June 10, 2004
• First Submitted That Met QC Criteria: June 10, 2004
• First Posted (Estimate): June 11, 2004

Study Record Updates

• Last Update Posted (Actual): December 22, 2020
• Last Update Submitted That Met QC Criteria: November 30, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: rectal cancer; colon cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: CDR0000367101; U01CA080098 (U.S. NIH Grant/Contract); U01CA079778 (U.S. NIH Grant/Contract); ACRIN-6664 (Other Identifier: CIP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Researchers may request data from the ACRIN data access committee by reviewing the information at:

https://www.acrin.org/RESEARCHERS/POLICIES/DATAANDIMAGESHARINGPOLICY.aspx

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No