Evaluation of Multi-Cancer Early Detection Testing in a High-Risk Population: The INFORM Study

The purpose of this research study is to evaluate the possible benefits and harms of screening with an investigational blood test designed to detect many types of cancer early.

The name of the screening blood test being studied is:

-GRAIL Galleri test

Study Overview

• Status: Recruiting
• Conditions: Cancer Predisposition Syndrome; Predisposition, Genetic
• Intervention / Treatment: Other: GRAIL Galleri Test

Detailed Description

This is a prospective, interventional study to assess the use of the GRAIL's Galleri multi-cancer early detection (MCED) Test, an investigational blood test designed to detect many types of cancer, for participants that are considered at slightly higher than average risk of developing certain types of cancers. The test looks for small pieces of genetic material called deoxyribonucleic acid (DNA) in the blood that may indicate the presence of cancer.

The research study procedures include screening for eligibility, blood tests, questionnaires, and clinic visits.

Participation in this research study is expected to last up to 3 years.

It is expected that about 1,000 people will take part in this research study.

• Study Type: Interventional
• Enrollment (Estimated): 1000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Elizabeth ODonnell, MD; Phone Number: 617-762-2334; Email: dfciprevention@mgb.org

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana-Farber Cancer Institute
      • Contact: Elizabeth ODonnell, MD; Phone Number: 587-215-2361; Email: elizabeth_odonnell@dfci.harvard.edu
      • Principal Investigator: Elizabeth ODonnell, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria Group 1- Cancer Predisposition Syndrome:

• Age ≥ 22 for patients with TP53 germline pathogenic variants, age ≥ 35 for all other variants in cancer predisposing genes
• Germline genetic testing revealed pathogenic germline variants in cancer predisposing genes (list of genes typically tested listed in pre-screening document)
• Individuals with a clinically based diagnosis of a Cancer Predisposition Syndrome (examples, neurofibromatosis, Fanconi Anemia, Ataxia-Telangiectasia)

Inclusion Criteria Group 2 - Familial Risk:

• Age ≥ 45

• Adults with family history suggestive of elevated cancer risk as defined by any the criteria below, who do not fall into Group 1:

  • ≥ 1 first or second degree relative on same side of the family with:

    • Breast, colon, gastric, endometrial, kidney cancer at or before age 50
    • Triple negative breast cancer (any age)
    • Male breast cancer (any age)
    • Ovarian, pancreatic, sarcoma cancer (any age)
    • Neuroendocrine cancer or tumors (any age)
    • Metastatic prostate cancer (any age)
    • Multiple primary cancers (example bilateral breast cancer)
  • ≥ 2 first or second degree relative on same side of the family (any combination is acceptable) with breast or prostate cancer at any age

Exclusion Criteria:

• Individuals diagnosed with invasive malignancy within 3 years of enrollment
• Have had a blood-based multi-cancer screening test within last year
• Individuals with evidence of symptomatic or active cancer requiring active therapeutic intervention at the time of participation (hormone therapy for breast/prostate cancer is considered acceptable and will not preclude participation)
• Individuals in Group 2 whose family history of cancer was the result of a germline mutation in a cancer predisposing gene and who have tested negative for that same familial germline mutation
• Individuals in Group 2 whose family history of cancer is sex-specific and who is a different sex than the proband with cancer (e.g., a male with a family history of endometrial or ovarian cancer would not be eligible)
• Individuals in process of being evaluated for clinical suspicion of cancer
• Individuals who have undergone a cancer risk-reducing surgery for hereditary cancer risk (e.g., mastectomy)

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: Galleri MCED Test; Participants will be enrolled and will complete: Baseline questionnaires and blood test.; Post-test questionnaires.; Follow-up assessments for a negative GRAIL Galleri test include recommended cancer screenings and a follow up phone call with study staff 1 year after the GRAIL Galleri blood test.; Follow-up assessments for a positive GRAIL test may include clinic visits, lab tests with additional blood work-ups, biopsies, surgical procedures, or imaging assessments such as ultrasound, Computed Tomography (CT) scans, or an Magnetic Resonance Imaging (MRI) scans.; If cancer status is confirmed, participants will complete a post-diagnostic questionnaire.

Other: GRAIL Galleri Test; A multi-cancer early detection (MCED) blood test.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cancer Detection Rate	Descriptive statistics will be used to summarize the number and types of cancers diagnosed by GRAIL Galleri MCED testing.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stage of Invasive Cancer Diagnosis	Descriptive statistics will be used to summarize the stages of invasive cancer that are diagnosed by GRAIL Galleri MCED testing and assessed by medical record review.	Up to 2 years
Positive Predictive Value At 12 Months	Positive Predictive Value is defined as the proportion of participants with cancer diagnosis out of all participants with "signal detected" on GRAIL Galleri MCED test results.	At 12 months
Positive Predictive Value at 24 Months	Positive Predictive Value is defined as the proportion of participants with cancer diagnosis out of all participants with "signal detected" on GRAIL Galleri MCED test results.	At 24 months
Time to Diagnostic Resolution	Defined as the time required to achieve diagnostic resolution following a "signal detected" GRAIL Galleri MCED test result.	Calculated from the date of return of screening results (up to 4 weeks from baseline) until up to 24 months post screening
Test Type Utilization to Diagnostic Resolution	Per participant the count of the number and types of diagnostic tests required to achieve diagnostic resolution following a "signal detected" GRAIL Galleri MCED test result.	Up to 24 months
Change in Participant Anxiety	Changes in anxiety following the GRAIL Galleri MCED test result and assessed by the Patient-Reported Outcome Measurement Information System (PROMIS) Emotional Distress Anxiety - Short Form 6a, which is a 6 item survey that is rated on a 5-point Likert scale with answers ranging from "Never" to "Always". The range of scoring is from 6 to 30 with higher scores indicating greater severity of anxiety.	Up to 24 months
Change in Participant Health-related Quality of Life	Changes in health-related quality of life following the GRAIL Galleri MCED test result and assessed by PROMIS Scale v1.2 - Global Health, a 10 item survey that is rated on a 5-point Likert scale with answers ranging from "Excellent/Completely/Never/None" to "Poor/Not at all/Always/Very Severe" and includes a pain average question rated on a scale of 0 "No Pain" to 10 "Worst Pain Imaginable." The range of scoring is from 9 to 45 with higher scores indicating higher quality of life.	Up to 24 months
Cost of Follow-up Testing	Defined as the dollar cost, per participant, of follow-up testing to achieve diagnostic resolution following a "signal detected" GRAIL Galleri MCED test result.	Up to 24 months
Institutional Reimbursement of Follow-up Testing	Defined as the dollar cost, per participant, of the institutional reimbursement of follow-up testing to achieve diagnostic resolution following a "signal detected" GRAIL Galleri MCED test result.	Up to 24 months

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute
• Investigators: Principal Investigator: Elizabeth ODonnell, MD, Dana-Farber Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2024
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2028

Study Registration Dates

• First Submitted: June 4, 2024
• First Submitted That Met QC Criteria: June 7, 2024
• First Posted (Actual): June 10, 2024

Study Record Updates

• Last Update Posted (Actual): January 20, 2026
• Last Update Submitted That Met QC Criteria: January 15, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Cancer Predisposition Syndrome; Predisposition, Genetic
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Disease Susceptibility; Pathological Conditions, Signs and Symptoms; Genetic Predisposition to Disease
• Other Study ID Numbers: 24-070

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Data can be shared no earlier than 1 year following the date of publication
• IPD Sharing Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No