Assessment of the Implementation of an Investigational Multi-Cancer Early Detection Test Into Clinical Practice

• ClinicalTrials.gov Identifier: NCT04241796
• Recruitment Status: Completed
• First Posted: January 27, 2020
• Last Update Posted: October 25, 2022
• Sponsor: GRAIL, LLC
• Information provided by (Responsible Party): GRAIL, LLC

Tracking Information

• First Submitted Date: January 2, 2020
• First Posted Date: January 27, 2020
• Last Update Posted Date: October 25, 2022
• Actual Study Start Date: December 12, 2019
• Actual Primary Completion Date: December 1, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 23, 2020)

• Per participant count of the number and types of diagnostic tests required to achieve diagnostic resolution following a "signal detected" multi-cancer early detection test result. [ Time Frame: Until diagnostic resolution or 12 months, whichever occurs first ]
• Per participant time required to achieve diagnostic resolution following a "signal detected" multi-cancer early detection test result. [ Time Frame: Until diagnostic resolution or 12 months, whichever occurs first ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 17, 2020)

• Positive Predictive Value defined as the proportion of participants with cancer diagnosis out of all participants with "signal detected" multi-cancer early detection test result. [ Time Frame: Up to 12 months ]
• Negative Predictive Value defined as the proportion of participants with no cancer diagnosis out of all participants with "signal not detected" results and completed EOS assessment. [ Time Frame: Up to 12 months ]
• Specificity defined as the proportion of participants with "signal not detected" results out of all participants with no cancer diagnosis and completed end of study (EOS) assessment. [ Time Frame: Up to 12 months ]
• Tissue of origin (TOO) accuracy defined as the proportion of correct TOO predictions in participants with determinate TOO returned by the multi-cancer early detection test and cancer diagnosis. [ Time Frame: Up to 12 months ]
• Perceptions of the multi-cancer early detection test result assessed by Adapted Multidimensional Impact of Cancer Risk Assessment (Adapted MICRA). Higher scores represent worse outcomes from 0-95. [ Time Frame: Up to 12 months ]
• Changes in health-related quality of life following the multi-cancer early detection test assessed by Short Form Health Survey (SF-12v2). [ Time Frame: Up to 12 months ]
  The SF-12v2 is a measure of health related quality of life. Higher values represent better health e.g. Physical Component Summary (PCS) range from 4.62 to 76.36 and Mental Component Summary (MCS) range from 1.32 to 79.48.
• Changes in anxiety following the multi-cancer early detection test result: Patient-reported Outcome Measurement Information System (PROMIS) Anxiety. [ Time Frame: Up to 12 months ]
  Assessed by Patient-reported Outcome Measurement Information System (PROMIS) Anxiety. Range in score from 4 to 20 with higher scores indicate greater severity of anxiety.
• Satisfaction with the multi-cancer early detection test: scores [ Time Frame: Up to 12 months ]
  Range in score from 0-100 with higher scores indicating higher satisfaction.

Original Secondary Outcome Measures (submitted: January 23, 2020)

• Perceptions of the multi-cancer early detection test result assessed by Adapted Multidimensional Impact of Cancer Risk Assessment (Adapted MICRA). Higher scores represent worse outcomes from 0-95. [ Time Frame: Up to 12 months ]
• Changes in health-related quality of life following the multi-cancer early detection test assessed by Short Form Health Survey (SF-12v2). [ Time Frame: Up to 12 months ]
  The SF-12v2 is a measure of health related quality of life. Higher values represent better health e.g. Physical Component Summary (PCS) range from 4.62 to 76.36 and Mental Component Summary (MCS) range from 1.32 to 79.48.
• Changes in anxiety following the multi-cancer early detection test result: Patient-reported Outcome Measurement Information System (PROMIS) Anxiety [ Time Frame: Up to 12 months ]
  Assessed by Patient-reported Outcome Measurement Information System (PROMIS) Anxiety. Range in score from 4 to 20 with higher scores indicate greater severity of anxiety.
• Satisfaction with the multi-cancer early detection test: scores [ Time Frame: Up to 12 months ]
  Range in score from 0-100 with higher scores indicating higher satisfaction.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Assessment of the Implementation of an Investigational Multi-Cancer Early Detection Test Into Clinical Practice
• Official Title: The PATHFINDER Study: Assessment of the Implementation of an Investigational Multi-Cancer Early Detection Test Into Clinical Practice
• Brief Summary: PATHFINDER is a prospective, multi-center study in which approximately 6,200 participants will be enrolled. An investigational multi-cancer early detection test, developed by GRAIL, will be ordered by and results returned to a study investigator. In cases with a "signal detected" test result (with a predicted or indeterminate tissue of origin (TOO)), the diagnostic work-up will not be dictated by the protocol, but will instead be coordinated by the ordering and treating medical team at the enrolling sites based on the participant's clinical condition, recommendations by each institution's clinical practices, and in consultation with the study investigator and interdisciplinary care team, as necessary. Additionally, proposed clinical care pathways, developed based on a review of guidelines from the National Comprehensive Cancer Network (NCCN), American College of Radiology (ACR) and other professional organizations, should be referenced by the medical team to determine the diagnostic work-up. The number and types of diagnostic procedures required to achieve diagnostic resolution will be assessed. Performance of multi-cancer early detection test will be evaluated. Additionally, participant-reported outcomes will be collected at several time points to assess participants' perceptions about the multi-cancer early detection test. Participants will be followed for approximately 12 months from the time of enrollment. Cancer status will also be assessed at the 12 month time point.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Screening
• Condition: Cancer

Intervention

Device: Multi-Cancer Early Detection Test

Blood collection and multi-cancer early detection testing with return of results.

Study Arms

Experimental: Elevated Risk and Non-Elevated Risk Groups

Two cohorts:

1. Elevated risk group (approximately 70% of the total enrollment) on the basis of history of smoking, documented genetic cancer predisposition, or personal history of invasive or hematologic malignancy.
2. Non-elevated risk group (approximately 30% of the total enrollment) with none of the conditions listed in the Elevated Risk Group.

Intervention: Device: Multi-Cancer Early Detection Test

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 22, 2022): 6662
• Original Estimated Enrollment (submitted: January 23, 2020): 6200
• Actual Study Completion Date: January 5, 2022
• Actual Primary Completion Date: December 1, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

Cohort A: Elevated Risk Group (70% of cohort):

• Age: Participant must be 50 years of age or older at the time of signing the Informed Consent Form (ICF).
• Participants must meet at least one of the criteria below:
• History of smoking at least 100 cigarettes in his or her lifetime
• Documented genetic cancer predisposition, hereditary cancer syndrome, or meeting criteria for germline testing based on current NCCN guidelines
• Personal history of invasive or hematologic malignancy, with definitive treatment completed greater than 3 years prior to enrollment. Adjuvant hormone therapy for cancer is permissible (ie may be ongoing within 3 years or at the time of enrollment).

Cohort B: Non-Elevated Risk Group (30% of cohort):

• Age: Participant must be 50 years of age or older, at the time of signing the Informed Consent Form (ICF).
• None of the conditions described in Cohort A, criteria 2a-c
• For all participants, capable of giving signed and legally effective informed consent

Exclusion Criteria:

• Undergoing or referred for diagnostic evaluation due to clinical suspicion for cancer (e.g., referred to a medical or surgical oncologist, or scheduled for biopsy on the basis of a suspicious imaging abnormality).
• Personal history of invasive or hematologic malignancy, diagnosed within the 3 years prior to expected enrollment date, or diagnosed greater than 3 years prior to expected enrollment date and never treated.
• Definitive treatment for invasive or hematologic malignancy within the 3 years prior to expected enrollment date. Adjuvant hormone therapy for cancer is not an exclusion criterion.
• Individuals who will not be able to comply with the protocol procedures.
• Individuals who are not current patients at a participating center.
• Previous or current participation in another GRAIL-sponsored study.
• Previous or current employees or contractors of GRAIL.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04241796
• Other Study ID Numbers: GRAIL-007
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: GRAIL, LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: GRAIL, LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: GRAIL, LLC
• Verification Date: October 2022