Bladder Carcinoma, Breast Carcinoma, Colorectal Carcinoma, Esophageal Carcinoma, Gastric Carcinoma, Liver Carcinoma, Lung Carcinoma, Malignant Solid Neoplasm, Ovarian Carcinoma, Pancreatic Carcinoma, Prostate Carcinoma
Conditions
Brief summary
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).
Detailed description
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. III. To develop preliminary estimates of the total and incremental budget impact of MCD testing compared to current screening practice from the payor perspective. IV. To develop preliminary estimates of the economic burden and impact of MCD testing from the participant perspective. V. To assess the willingness of participants who reported military service to describe military-related environmental exposures by completing the Military Exposure Questionnaire. 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.
Interventions
PROCEDUREBiospecimen Collection
Undergo blood collection
DEVICEDevice Usage
Evaluation of MCD tests
OTHERElectronic Health Record Review
Obtain health data
PROCEDUREMulti-Cancer Detection Test
Undergo Shield MCD test
OTHERQuestionnaire Administration
Study specific questionnaires
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SCREENING
Masking
SINGLE (Subject)
Masking description
Four ACCESS Hubs will institute participant blinding to their randomly assigned group. Participants recruited in the remaining ACCESS Hubs will be told the arm to which they have been assigned. The purpose of having some Hubs institute blinding and others unblinded is to assess the impact of blinding on recruitment, participation in standard of care cancer screening, and adherence to the study protocol.
Eligibility
Sex/Gender
ALL
Age
45 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Ages 45-75 years old * Agree to provide blood samples for possible MCD testing at enrollment and at 1 year following enrollment * Agree to allow collection of information from their medical records for study-related purposes * Understand and be able to complete informed consent and participant questionnaires in English, Spanish, or Arabic * Note: Eligibility for Spanish and Arabic languages are at the Hub's discretion
Exclusion criteria
* Solid malignant tumor or blood cancer diagnosis, with or without treatment, within the last 5 years * Note: Persons with a history of in situ cancers (e.g., ductal carcinoma in situ of the breast, cervical cancer in situ, atypical melanocytic hyperplasia or melanoma in situ) or nonmelanoma skin cancer are eligible. Persons with a history of prostate cancer that has not been treated are not eligible, regardless of when the diagnosis occurred * Ongoing cancer diagnostic work-up * Ongoing participation in another study of an investigational cancer screening test or technology not currently utilized in routine clinical practice * Currently breastfeeding or pregnant, or planning to become pregnant in the next year * History of solid organ or hematopoietic transplantation at any time, or blood transfusion within the last 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Staggered start of intervention arm 2 | Up to 1 year | Advantages and challenges arising from trial activation with one intervention arm and later addition of a second intervention arm. |
| Feasibility of enrollment onto study | At time of randomization | The number of participants enrolled into the study compared to trial goals. |
| Proportion of participants who complete baseline and follow-up questionnaires within 60 days of receipt | Up to 3 years | The proportion of participants who are complete questionnaires and timing of completion. |
| 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 | Up to 2 years | The proportion of participants who have a second blood draw and the timing of the blood draw. |
| Proportion of participants considered lost to follow-up within 2 years of randomization | Up to 2 years | The proportion of participants who do not complete study procedures and are not able to be contacted. |
| Representative enrollment | Up to 2 years | Meeting or exceeding the trial enrollment goals on a population basis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Specificity of each MCD assay | 1 year | Specificity will be estimated for each MCD assay. |
| Test positive rates | Up to 2 years | The proportion of abnormal MCD tests at each screening episode, and the proportion of participants with at least one abnormal test. |
| False positives | Up to 2 years | The number of participants with an abnormal MCD test and no cancer diagnosis. |
| Impact of participant blinding | Up to 2 years | Comparisons between blinded and unblinded sites on participation rates, adherence to protocol-required questionnaires and blood collection, and participation in standard of care screening. |
| Timely return of MCD test result | Up to 2 years | 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. |
| Factors contributing to lack of diagnostic resolution of an abnormal MCD test | Up to 2 years | Factors that contribute to the inability to determine if a participant has a cancer or rule out cancer. |
| Contamination | Up to 3 years | Estimated as the number of participants receiving MCD testing outside the trial. |
| Effects of participant characteristics | Up to 2 years | Feasibility outcomes will be reported by participant demographics and cancer risk factors. |
| Diagnostic resolution following an abnormal MCD test result | Within 12 months 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 to diagnostic resolution | Up to 2 years | The number of days from date of ACCESS Hub receipt of abnormal MCD test result to date of provider-reported diagnostic resolution. |
| Participation in standard of care screening | Up to 2 years | The proportion of participants that receive standard of care cancer screening in each arm. |
| Accuracy of tissue of origin prediction | Up to 2 years | The proportion of diagnosed cancers that match the tissue of origin predicted by an abnormal (positive) MCD test, for each screening episode. |
| Complications related to diagnostic evaluation of an abnormal MCD test result | Up to 1 year | Adverse events occurring in participants undergoing a diagnostic workup following receipt of an abnormal MCD test result. |
| (Targeted cancer) Positive predictive value (PPV) | Up to 2 years | 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. |
| Anxiety and Cancer Worry Questionnaire | Up to 2 years | 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. |
| (All cancer) PPV | Up to 2 years | 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. |
| Interval cancers | 1 year | 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. |
| Detected cancers | 1 year | 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. |
| (Targeted cancer) Negative predictive value | 1 year | 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. |
| Sensitivity of clinical diagnostic performance of each MCD assay | Up to 2 years | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORScott D Ramsey
Fred Hutchinson Cancer Center
Outcome results
None listed