Colorectal Lesion Evaluation and Appropriate Resolution (CLEAR) Study

Pilot Study to Evaluate a Blood Based Test to Prioritize Diagnostic Colonoscopy Following a Positive Colorectal Cancer Screening Test (CLEAR Study)

The primary objective of this study is to evaluate a blood-based screening test for Colorectal Cancer (CRC).

Participants 45 years and older who are at average risk for colorectal cancer (CRC) with a positive multitarget stool DNA (mt-sDNA) screening test result and scheduled to undergo diagnostic colonoscopy as part of standard clinical care within 60 days of providing informed consent (Cohort 1), and participants with confirmed CRC diagnosed within 90 days prior to providing informed consent, based on standard diagnostic procedures (Cohort 2), will be enrolled. Participants enrolled with confirmed CRC must be treatment-naïve at the time of enrollment. A one-time blood sample will be collected from all enrolled participants within 14 days of signing the informed consent form. Participation will be completed when the participant completes the blood draw, and after the participant's cancer status is established (at enrollment for those enrolled with confirmed CRC (Cohort 2), and by 60 days post-colonoscopy for those in the prospective cohort (Cohort 1)). Participants in Cohort 1 may be directly contacted after enrollment if diagnosis details are not available in the medical records. It is expected that study enrollment will take approximately 12 months. Results generated from study samples are investigational and will not be returned to investigators, study participants, or participants' healthcare providers, and will not be used for clinical decision-making.

Inclusion Criteria:

• Cohort 1: Prospective Cohort Inclusion criteria - All Participants must meet the following criteria to be included in the study:

  1. Provide written or electronic informed consent, according to local guidelines, signed and dated by the Participant or by a legal guardian prior to the performance of any study-specific procedures, sampling, or analyses
  2. Age 45 or older at time of consent
  3. Documented positive result from a mt-sDNA test obtained as part of routine clinical care within 12 months of blood draw
  4. Scheduled and intends to undergo a diagnostic colonoscopy within 60 days of consent as part of standard care
  5. Considered by a physician as being of average risk for CRC
  6. Willing to provide an investigational blood draw prior to undergoing bowel preparation administration and colonoscopy.

• Cohort 2: Confirmed Case Cohort Inclusion criteria - All Participants must meet the following criteria to be included in the study:

  1. Provide written or electronic informed consent, according to local guidelines, signed and dated by the Participant or by a legal guardian prior to the performance of any study-specific procedures, sampling, or analyses
  2. Age 45 or older at time of consent
  3. Has a confirmed CRC diagnosis within 90 days prior to signing the informed consent form, based on standard diagnostic procedures
  4. Must remain treatment-naïve for the current malignancy (no surgical resection, neoadjuvant chemotherapy, or radiation therapy has occurred since diagnosis)

Exclusion Criteria:

• Cohort 1: Prospective Cohort Exclusion Criteria - Participants who meet any of the following criteria will be excluded from study entry:

  1. Undergoing colonoscopy for investigation of symptoms such as rectal bleeding, blood in stool, or significant recent changes in stool habits
  2. History of CRC or AA diagnosed prior to the index mtsDNA positive test result
  3. History of any malignancy (patients who have undergone surgical removal of skin basal cell or squamous cell cancer may be enrolled provided the procedure was completed at least 12 months prior to the date of informed consent)
  4. Has been diagnosed with a condition associated with a high risk of CRC (including inflammatory bowel disease (IBD), chronic ulcerative colitis, Crohn's disease, or familial adenomatous polyposis) or has a family history of CRC, defined as having a first-degree relative (parent, sibling, or child) with a CRC diagnosis at any age
  5. Has been diagnosed with a relevant familial (hereditary) cancer syndrome that places them above average risk of CRC such as hereditary nonpolyposis CRC syndrome (or Lynch syndrome), Peutz-Jeghers syndrome, MYH-associated polyposis, Gardner's syndrome, Turcot's (or Crail's) syndrome, Cowden's syndrome, juvenile polyposis, Cronkhite-Canada syndrome, neurofibromatosis, or familial hyperplastic polyposis
  6. Is suffering from any febrile illness defined as a temperature >101.5°F within 48 hours preceding the blood draw
  7. Participant is pregnant (self-reported)
  8. Recipient of an organ transplant, blood transfusion within 120 days, or prior non-autologous (allogeneic) bone marrow or stem cell transplant (Participants with a corneal transplant can be considered for study entry)
  9. Inability or unwillingness to comply with study procedures or follow-up requirements
  10. Previous or current participation in any study sponsored by, or employment with, Harbinger Health
  11. Participation in a clinical research study sponsored by an external organization which may interfere with study procedures or outcomes
  12. Has any condition that in the opinion of the Investigator should preclude participation in the study

• Cohort 2: Confirmed Case Cohort Exclusion Criteria - Participants who meet any of the following criteria will be excluded from study entry:

  1. Has a history of any malignancy (patients who have undergone surgical removal of skin basal cell or squamous cell cancer may be enrolled provided the procedure was completed at least 12 months prior to the date of informed consent for the study)
  2. Is suffering from any febrile illness defined as a temperature >101.5°F within 48 hours preceding the blood draw
  3. Participant is pregnant (self-reported)
  4. Is a recipient of an organ transplant, blood transfusion within 120 days, or prior non-autologous (allogeneic) bone marrow or stem cell transplant (Participants with a corneal transplant can be considered for study entry)
  5. Inability or unwillingness to comply with study procedures or follow-up requirements
  6. Previous or current participation in any study sponsored by, or employment with, Harbinger Health
  7. Participation in a clinical research study sponsored by an external organization which may interfere with study procedures or outcomes
  8. Has any condition that in the opinion of the Investigator should preclude participation in the study.