The Vanguard Study is a feasibility study to explore several aspects of evaluating multi-cancer detection (MCD) tests in a future definitive randomized controlled trial. An MCD test measures markers in the blood in order to screen for multiple cancers simultaneously. There is a need to understand how MCDs may work as cancer screening tools. The goal of cancer screening is to reduce the burden of cancer by identifying cancers before they show symptoms or signs, when treatment is likely to be most effective. In this study, adults aged 45-75 without cancer will be randomly assigned to one of 3 groups: 2 separate MCD test groups or a control group. These two MCD tests will not be compared to each other but will be compared to cancers detected in the control group. This study will provide early information on how well MCD tests perform as cancer screening tools. It will also help researchers understand how patients and their doctors make decisions about their care when the MCD test result comes back as normal (negative) or abnormal (positive).
PRIMARY OBJECTIVES: I. Assess the feasibility of recruitment and adherence to protocol-required baseline and follow-up data and blood collection. II. Assess the feasibility of achieving representative enrollment across participating recruitment sites. SECONDARY OBJECTIVES: I. To assess the impact of participant blinding on willingness to participate, adherence to protocol required baseline and follow-up data, blood collection, and rates of standard of care screening. II. To determine the timeliness of returning test results to participants. III. To understand the factors contributing to lack of diagnostic resolution of an abnormal MCD test. IV. To examine the effects of participant characteristics, including cancer risk factors and social determinants of health, on all aspects of feasibility. V. To estimate the proportion of participants receiving an MCD test outside of the trial. VI. To assess the feasibility of a staggered introduction of the second MCD assay intervention arm. VII. To estimate the proportion of abnormal MCD tests that are diagnostically resolved, and the time to resolution. VIII. To compare the proportion of participants who receive standard of care screening during follow-up between the intervention and control arms. IX. To assess the accuracy of tissue of origin prediction for each MCD assay. X. To estimate the incidence of complications related to diagnostic evaluation of an abnormal MCD test result. XI. To assess the effect of an abnormal MCD test and diagnostic workup on anxiety and cancer worry. XII. To evaluate the clinical diagnostic performance of the MCD assays. EXPLORATORY OBJECTIVES: I. To estimate rates of late-stage cancer, and the distribution of cancer stage. II. To estimate assay-targeted cancer-specific mortality of each MCD assay, all cancer-specific mortality, and all-cause mortality. OUTLINE: Participants are randomized to 1 of 3 arms. ARM I: Participants undergo blood collection for Shield MCD testing at enrollment and after one year on study. Participants at unblinded sites are provided results of tests and those with abnormal results follow up with their clinician for additional testing. Participants at blinded sites are provided abnormal results and will follow up with their clinician for additional testing. ARM II: Participants undergo blood collection for Avantect MCD testing at enrollment and after one year on study. Participants at unblinded sites are provided results of tests and those with abnormal results follow up with their clinician for additional testing. Participants at blinded sites are provided abnormal results and will follow up with their clinician for additional testing. ARM III (Control): Participants undergo blood collection at enrollment and after one year on study. After completion of study intervention, participants are followed passively up to 10 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SCREENING
Masking
SINGLE
Enrollment
24,000
Undergo blood collection
Evaluation of MCD tests
Obtain health data
Undergo Shield MCD test
Undergo Avantect MCD test
Study specific questionnaires
Kaiser Permanente-Division of Research
Pleasanton, California, United States
RECRUITINGKeefe Memorial Hospital
Cheyenne Wells, Colorado, United States
RECRUITINGKaiser Permanente-Franklin
Denver, Colorado, United States
RECRUITINGPoudre Valley Hospital
Fort Collins, Colorado, United States
Feasibility of enrollment onto study
The number of participants enrolled into the study compared to trial goals.
Time frame: At time of randomization
Proportion of participants who complete baseline and follow-up questionnaires within 60 days of receipt
The proportion of participants who are complete questionnaires and timing of completion.
Time frame: Up to 3 years
Proportion of participants who provide the required blood sample for year 1 for Multi-Cancer Detection (MCD) testing within 90 days of recommended time point
The proportion of participants who have a second blood draw and the timing of the blood draw.
Time frame: Up to 2 years
Proportion of participants considered lost to follow-up within 2 years of randomization
The proportion of participants who do not complete study procedures and are not able to be contacted.
Time frame: Up to 2 years
Representative enrollment
Meeting or exceeding the trial enrollment goals on a population basis.
Time frame: Up to 2 years
Staggered start of intervention arm 2
Advantages and challenges arising from trial activation with one intervention arm and later addition of a second intervention arm.
Time frame: Up to 1 year
Impact of participant blinding
Comparisons between blinded and unblinded sites on participation rates, adherence to protocol-required questionnaires and blood collection, and participation in standard of care screening.
Time frame: Up to 2 years
Timely return of MCD test result
The time from receipt of the MCD test result at the Statistics and Data Management Center to the time of receipt of the MCD test result at the ACCESS Hub. The time from receipt of MCD test result at the ACCESS Hub to the time of participant receipt of the MCD test result.
Time frame: Up to 2 years
Factors contributing to lack of diagnostic resolution of an abnormal MCD test
Factors that contribute to the inability to determine if a participant has a cancer or rule out cancer.
Time frame: Up to 2 years
Contamination
Estimated as the number of participants receiving MCD testing outside the trial.
Time frame: Up to 3 years
Effects of participant characteristics
Feasibility outcomes will be reported by participant demographics and cancer risk factors.
Time frame: Up to 2 years
Diagnostic resolution following an abnormal MCD test result
The proportion of participants with a "cancer diagnosis" or "no cancer diagnosis" among all participants with an abnormal MCD test result
Time frame: Within 12 months following an abnormal MCD test result
Time to diagnostic resolution
The number of days from date of ACCESS Hub receipt of abnormal MCD test result to date of provider-reported diagnostic resolution.
Time frame: Up to 2 years
Participation in standard of care screening
The proportion of participants that receive standard of care cancer screening in each arm.
Time frame: Up to 2 years
Accuracy of tissue of origin prediction
The proportion of diagnosed cancers that match the tissue of origin predicted by an abnormal (positive) MCD test, for each screening episode.
Time frame: Up to 2 years
Complications related to diagnostic evaluation of an abnormal MCD test result
Adverse events occurring in participants undergoing a diagnostic workup following receipt of an abnormal MCD test result.
Time frame: Up to 1 year
Anxiety and Cancer Worry Questionnaire
Participant anxiety will be assessed with the Patient Reported Outcomes Measurement Information System instrument. Cancer-related worry will be assessed using the Lehrman Cancer Worry Scale.
Time frame: Up to 2 years
Sensitivity of clinical diagnostic performance of each MCD assay
Sensitivity will be estimated for each MCD assay. These sensitivities will also be calculated by early- versus late-stage, and for MCD test-targeted cancers and all cancers.
Time frame: Up to 2 years
Specificity of each MCD assay
Specificity will be estimated for each MCD assay.
Time frame: 1 year
Test positive rates
The proportion of abnormal MCD tests at each screening episode, and the proportion of participants with at least one abnormal test.
Time frame: Up to 2 years
False positives
The number of participants with an abnormal MCD test and no cancer diagnosis.
Time frame: Up to 2 years
(Targeted cancer) Positive predictive value (PPV)
The proportion of abnormal MCD tests that result in diagnosis of one of the MCD test-targeted cancers among participants with at least one abnormal test, for each screening episode.
Time frame: Up to 2 years
(All cancer) PPV
The proportion of abnormal MCD tests that result in diagnosis of any cancer among participants with at least one abnormal test, for each screening episode.
Time frame: Up to 2 years
Interval cancers
The number of MCD test-targeted cancer cases diagnosed within 12 months of a normal MCD test result among participants who received an MCD test, for each screening episode.
Time frame: 1 year
Detected cancers
The number of cancer cases diagnosed within a 12-month follow-up period of an abnormal test result among participants who received an MCD test, for each screening episode.
Time frame: 1 year
(Targeted cancer) Negative predictive value
The proportion of normal MCD tests that did not result in diagnosis of one of the MCD test-targeted cancers among participants with a normal test, for each screening episode.
Time frame: 1 year
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Cancer Care and Hematology-Fort Collins
Fort Collins, Colorado, United States
RECRUITINGUCHealth Greeley Hospital
Greeley, Colorado, United States
RECRUITINGKaiser Permanente-Rock Creek
Lafayette, Colorado, United States
RECRUITINGKaiser Permanente-Lone Tree
Lone Tree, Colorado, United States
RECRUITINGMedical Center of the Rockies
Loveland, Colorado, United States
RECRUITINGKaiser Permanente Moanalua Medical Center
Honolulu, Hawaii, United States
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