Does Screening With the Galleri Test in the NHS Reduce the Likelihood of a Late-stage Cancer Diagnosis in an Asymptomatic Population? A Randomised Clinical Trial

N/AActive Not RecruitingNCT05611632

GRAIL, Inc.142,318 enrolled

Overview

The Galleri test is a new test that looks for potential signs of cancer in a blood sample. The test can find many different types of cancer but cannot find all cancers. The trial aims to see if using the Galleri test alongside standard cancer testing in the NHS can help to find cancers at an early stage when they are easier to treat. The trial has enrolled approximately 140,000 participants who will be actively followed for approximately three years from the date of enrollment.

This is a prospective, randomized, controlled trial to assess the performance and clinical utility of a multi-cancer early detection test for population screening in the UK when added to standard of care. Participants and the study teams remain blinded throughout the study with the exception of the study nurses returning the results and a small number of staff to enable them to perform administrative duties. Blinding is maintained for participants with the exception of those participants who test positive. Those who test positive will be informed by designated trial staff and will be referred for standard of care investigations and treatment. Trial sponsor employees, the CIs and site staff (unless identified differently in the blinding plan for study conduct needs) will remain blinded throughout the study. Randomization will be to either the intervention arm, with blood collection and evaluation of the test with consequent investigation and treatment of a positive test through referral to the NHS urgent two week wait pathway, or to the control arm, where blood samples are collected at designated intervals and will be stored for potential future evaluation, but participants do not receive test results and otherwise continue to receive routine NHS care. Unless diagnosed with cancer, participants in both arms will be asked to return for annual visits at approximately 12 and 24 months. All participants whether test positive, test negative or not tested will be followed for cancer and associated outcomes via NHS dataset linkages.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

SCREENING

Masking

Eligibility

Sex: ALLMin age: 50 YearsMax age: 77 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. Participants must be at 50-77 years of age, inclusive, at the time of data extraction from NHS datasets or GP records used to identify potential participants; and 2. Capable of giving signed and legally effective informed consent, which includes compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and in this protocol. Consent provided by a legally authorised representative is not permitted in this protocol. Exclusion Criteria: 1. Previous or current participation in another GRAIL-sponsored study. 2. Personal history of invasive cancer or haematologic malignancy, diagnosed within the three years prior to expected enrolment date. Note: Individuals with a diagnosis of non-melanoma skin cancer and prostate cancer patients whose only treatment is active surveillance are NOT excluded 3. Definitive treatment for invasive cancer or haematologic malignancy within the 3 years prior to expected enrolment date, including adjuvant hormone therapy for cancer (e.g. for breast or prostate cancer). 4. Currently taking demethylating or cytotoxic agents for any condition. 5. Undergoing current investigation for suspected cancer, defined as having been referred to a two week wait clinic or undergoing investigations at an RDC or other clinic with a stated suspicion of cancer. 6. Currently on a palliative care pathway.

Outcomes

Primary Outcomes

incidence of stage III and IV cancers diagnosed in the intervention arm as compared with the control arm

using a fixed-sequence statistical strategy as below: * first, evaluate for a statistically significant difference in a prespecified group of primary cancer types: lung, head \& neck, colorectal, pancreas, myeloma/plasma cell neoplasm, liver/bile duct, stomach, oesophagus, anus, lymphoma, ovary, and bladder. * if a statistically significant reduction in absolute numbers is found, continue by evaluating for a difference in all cancer types excluding prostate cancer. * If the above evaluations are both significant, evaluate for a difference in all cancer types.

Time frame: 3-4 years after randomization

Secondary Outcomes

incidence of advanced cancers (stage III and IV cancers or one that results in a cancer-specific death) diagnosed in the intervention arm as compared with the control arm.

Time frame: 3-4 years after randomization

incidence of stage IV cancers diagnosed in the intervention arm as compared with the control arm

sequentially: * for a prespecified group of 12 cancer types: lung, head \& neck, colorectal, pancreas, myeloma/plasma cell neoplasm, liver/bile duct, stomach, esophagus, anus, lymphoma, ovary, and bladder. * for all cancer types excluding prostate cancer. * for all cancer types.

Time frame: 1 year after randomization

incidence of all cancers diagnosed in the intervention arm as compared with the control arm

Time frame: 1 year after randomization

incidence of stage IV cancers following the second blood draw and 12 months of follow-up, with prevalent cases excluded

Time frame: 2 years after randomization

incidence of stage IV cancers diagnosed in the intervention arm as compared with the control arm.

Time frame: 3-4 years after randomization

modelled cancer mortality at 7 years post-randomization based on cancers diagnosed within 3-4 years after randomization in the intervention arm as compared with the control arm.

Time frame: 3-4 years after randomization

stage distribution by cancer type for the two arms.

Time frame: 3-4 years after randomization

incidence of stage III and IV cancers excluding breast, cervical, and colorectal diagnosed in the intervention arm as compared with the control arm.

Time frame: 3-4 years after randomization

incidence of stage III/ IV cancers following the third blood draw.

Time frame: 3-4 years after randomization

overdiagnosis by comparing the cumulative number of cancers diagnosed within 3-4 years of randomisation in individuals with a positive baseline test (evaluated retrospectively in the control arm) between arms.

Time frame: 3-4 years after randomization

cancer-specific mortality in the intervention arm as compared with the control arm.

specifically: * nested cancer-specific mortality up to 5 years after randomization. * cancer-specific mortality (up to 5 years and) up to 8 years after randomization.

Time frame: up to 8 years after randomization

proportion of stage I and II cancers in the intervention arm as compared with the control arm in the third screening round.

Time frame: 3-4 years after randomization

test performance (sensitivity, specificity, positive predictive value, negative predictive value) and cancer signal origin accuracy) in the intervention arm.

Time frame: Up to 3 years after randomization

participant-reported psychological impact including anxiety, at various timepoints in all test positive cases.

Time frame: Up to 1 year after randomization

number and type of invasive procedures performed, and complications and deaths associated with follow-up diagnostic procedures in all test positive cases.

Time frame: Up to 3 years after randomization

radiation exposure by participants associated with follow-up diagnostic procedures following a positive MCED test result.

Time frame: Up to 3 years after randomization

use of the MCED test across three annual timepoints on healthcare resource utilization for cancer diagnosis and treatment.

Time frame: Up to 3 years after randomization

Does Screening With the Galleri Test in the NHS Reduce the Likelihood of a Late-stage Cancer Diagnosis in an Asymptomatic Population? A Randomised Clinical Trial

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes