Bladder CarcinomaNCT06995898
The Vanguard Study: Testing a New Way to Screen for Cancer
A study testing Biospecimen Collection, Device Usage and Electronic Health Record Review in people with Bladder Carcinoma and Breast Carcinoma, run by National Cancer Institute (NCI) at 45 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 45 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Bladder Carcinoma, Breast Carcinoma, Colorectal Carcinoma
- What is being tested?
- Biospecimen Collection, Device Usage and Electronic Health Record Review
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24,000 participants
- Where
- 45 sitesUnited States
- Study dates
- 18 Jun 2025to 30 Jun 2029
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
45 sites in 1 country. Contact the study team or a site near you to ask about taking part.
45 sites in 1 country
United States45 sites, 45 recruiting
- Recruiting
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889-5600
Site Public Contact, 240-265-9823
Kristen Natale
- Recruiting
Henry Ford Cancer Institute-Downriver
Brownstown, Michigan, 48183
Site Public Contact, 313-916-3721, CTOResearch@hfhs.org
Christine Neslund-Dudas
- Recruiting
Henry Ford Health Center - Brownstown
Brownstown, Michigan, 48183
Site Public Contact, 313-874-5472, CDUDAS1@hfhs.org
Christine Neslund-Dudas
- Recruiting
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Site Public Contact, 877-668-0683, cancerclinicaltrials@med.unc.edu
Daniel S. Reuland
- Recruiting
Sentara Martha Jefferson Hospital
Charlottesville, Virginia, 22911
Site Public Contact, 434-654-8400
John M. Sayles
- Recruiting
Henry Ford Health Center - Chesterfield
Chesterfield, Michigan, 48047
Site Public Contact, 313-874-5472, CDUDAS1@hfhs.org
Christine Neslund-Dudas
- Recruiting
Keefe Memorial Hospital
Cheyenne Wells, Colorado, 80810
Site Public Contact, 719-767-5661, cmillsap@keefemh.org
Linda S. Cook
- Recruiting
Louis Stokes Cleveland VA Medical Center
Cleveland, Ohio, 44106
Site Public Contact, holly.henry@va.gov
Charles J. Nock
- Recruiting
Henry Ford Macomb Hospital-Clinton Township
Clinton Township, Michigan, 48038
Site Public Contact, 313-916-3721, CTOResearch@hfhs.org
Christine Neslund-Dudas
- Recruiting
Henry Ford Medical Center-Fairlane
Dearborn, Michigan, 48126
Site Public Contact, 313-916-3721, CTOResearch@hfhs.org
Christine Neslund-Dudas
- Recruiting
Kaiser Permanente-Franklin
Denver, Colorado, 80205
Site Public Contact, 303-817-9295, KPCOIHRClinicalResearch@kp.org
Debra P. Ritzwoller
- Recruiting
Henry Ford Hospital
Detroit, Michigan, 48202
Site Public Contact, 313-916-3721, CTOResearch@hfhs.org
Christine Neslund-Dudas
- Recruiting
Henry Ford Medical Center - Detroit Northwest
Detroit, Michigan, 48235
Site Public Contact, kkeenan1@hfhs.org
Christine Neslund-Dudas
- Recruiting
Durham VA Medical Center
Durham, North Carolina, 27705
Site Public Contact, 919-286-0411, VHADURcancertrials@va.gov
Scott Shofer
- Recruiting
Inova Schar Cancer Institute
Fairfax, Virginia, 22031
Site Public Contact, 703-720-5210, Stephanie.VanBebber@inova.org
Rebecca D. Kaltman
- Recruiting
Inova Fair Oaks Hospital
Fairfax, Virginia, 22033
Site Public Contact, 703-720-5210, Stephanie.VanBebber@inova.org
Rebecca D. Kaltman
- Recruiting
Poudre Valley Hospital
Fort Collins, Colorado, 80524
Site Public Contact, 970-297-6150
Linda S. Cook
- Recruiting
Cancer Care and Hematology-Fort Collins
Fort Collins, Colorado, 80528
Site Public Contact, 888-823-5923, ctsucontact@westat.com
Linda S. Cook
- Recruiting
UCHealth Greeley Hospital
Greeley, Colorado, 80631
Site Public Contact, 888-823-5923, ctsucontact@westat.com
Linda S. Cook
- Recruiting
Henry Ford Medical Center-Cottage
Grosse Pointe Farms, Michigan, 48236
Site Public Contact, 313-916-1784
Christine Neslund-Dudas
- Recruiting
Kaiser Permanente Moanalua Medical Center
Honolulu, Hawaii, 96819
Site Public Contact, 808-432-5195, shelley.a.clark@kp.org
Stacey Honda
- Recruiting
Saint Luke's Hospital of Kansas City
Kansas City, Missouri, 64111
Site Public Contact, 913-948-5588, aroland@kccop.org
Timothy J. Pluard
- Recruiting
Kaiser Permanente-Rock Creek
Lafayette, Colorado, 80026
Site Public Contact, 303-817-9295, KPCOIHRClinicalResearch@kp.org
Debra P. Ritzwoller
- Recruiting
Henry Ford Medical Center - Livonia
Livonia, Michigan, 48150
Site Public Contact, kkeenan1@hfhs.org
Christine Neslund-Dudas
- Recruiting
Kaiser Permanente-Lone Tree
Lone Tree, Colorado, 80124
Site Public Contact, 303-817-9295, KPCOIHRClinicalResearch@kp.org
Debra P. Ritzwoller
- Recruiting
Medical Center of the Rockies
Loveland, Colorado, 80538
Site Public Contact, 970-203-7083
Linda S. Cook
- Recruiting
Zablocki Veterans Administration Medical Center
Milwaukee, Wisconsin, 53295
Site Public Contact, 888-469-6614
Jeffrey C. Whittle
- Recruiting
Minneapolis VA Medical Center
Minneapolis, Minnesota, 55417
Site Public Contact, 612-467-2800
Mark A. Klein
- Recruiting
Sentara Norfolk General Hospital
Norfolk, Virginia, 23507
Site Public Contact, 757-388-2406
John M. Sayles
- Recruiting
Henry Ford Medical Center-Columbus
Novi, Michigan, 48377
Site Public Contact, 313-916-3721, CTOResearch@hfhs.org
Christine Neslund-Dudas
- Recruiting
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Site Public Contact, 405-271-8777, ou-clinical-trials@ouhsc.edu
Mark Doescher
- Recruiting
Kaiser Permanente-Division of Research
Pleasanton, California, 94588
Site Public Contact, 510-891-3400
Jeffrey Lee
- Recruiting
Henry Ford Medical Center - Plymouth
Plymouth, Michigan, 48170
Site Public Contact, kkeenan1@hfhs.org
Christine Neslund-Dudas
- Recruiting
Naval Medical Center - Portsmouth
Portsmouth, Virginia, 23708-2197
Site Public Contact, 757-953-5939
John C. Mattingly
- Recruiting
VCU Massey Cancer Center at Stony Point
Richmond, Virginia, 23235
Site Public Contact, ctoclinops@vcu.edu
Alexander H. Krist
- Recruiting
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298
Site Public Contact, 804-628-6430, CTOclinops@vcu.edu
Alexander H. Krist
- Recruiting
Henry Ford Medical Center - Royal Oak
Royal Oak, Michigan, 48067
Site Public Contact, kkeenan1@hfhs.org
Christine Neslund-Dudas
- Recruiting
VCU Community Memorial Health Center
South Hill, Virginia, 23970
Site Public Contact, nemer.elmouallem@vcuhealth.org
Alexander H. Krist
- Recruiting
CoxHealth South Hospital
Springfield, Missouri, 65807
Site Public Contact, 417-269-4520
Aimee S. James
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Site Public Contact, 800-600-3606, info@siteman.wustl.edu
Aimee S. James
- Recruiting
Henry Ford Medical Center
Sterling Heights, Michigan, 48310
Site Public Contact, 888-823-5923, ctsucontact@westat.com
Christine Neslund-Dudas
- Recruiting
Madigan Army Medical Center
Tacoma, Washington, 98431
Site Public Contact, 253-968-6144, melissa.a.forouhar.mil@health.mil
Matthew Lavoie
- Recruiting
Henry Ford Medical Center - Troy
Troy, Michigan, 48083
Site Public Contact, kkeenan1@hfhs.org
Christine Neslund-Dudas
- Recruiting
Henry Ford West Bloomfield Hospital
West Bloomfield, Michigan, 48322
Site Public Contact, 313-916-3721, CTOResearch@hfhs.org
Christine Neslund-Dudas
- Recruiting
Henry Ford Wyandotte Hospital
Wyandotte, Michigan, 48192
Site Public Contact, nhay@hfhs.org
Christine Neslund-Dudas
About this study
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).
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- 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:
- 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.
- 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.
- Conditions
- Bladder Carcinoma, Breast Carcinoma, Colorectal Carcinoma, Esophageal Carcinoma, Gastric Carcinoma, Liver Carcinoma
- Being tested
- Biospecimen Collection, Device Usage, Electronic Health Record Review, Multi-Cancer Detection Test, Questionnaire Administration
- Medical subject headings
- Urinary Bladder Neoplasms, Breast Neoplasms, Colorectal Neoplasms, Esophageal Neoplasms, Stomach Neoplasms, Carcinoma, Hepatocellular, Lung Neoplasms, Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo blood collection
Device UsageDevice
Also called Usage of Device
Evaluation of MCD tests
Electronic Health Record ReviewOther
Obtain health data
Multi-Cancer Detection TestProcedure or surgery
Also called MCD Assay, MCD Test, MCED Assay, MCED Test
Undergo Shield MCD test
Multi-Cancer Detection TestProcedure or surgery
Also called MCD Assay, MCD Test, MCED Assay, MCED Test
Undergo Avantect MCD test
Questionnaire AdministrationOther
Study specific questionnaires
| Study group | Role | What they receive |
|---|---|---|
| Arm I (Shield MCD test) | Experimental | 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. Receives: Procedure: Biospecimen Collection; Device: Device Usage; Other: Electronic Health Record Review; Procedure: Multi-Cancer Detection Test; Other: Questionnaire Administration |
| Arm II (Avantect MCD test) | Experimental | 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. Receives: Procedure: Biospecimen Collection; Device: Device Usage; Other: Electronic Health Record Review; Procedure: Multi-Cancer Detection Test; Other: Questionnaire Administration |
| Arm III (Control) | Active comparator | Participants undergo blood collection at enrollment and after one year on study. Receives: Procedure: Biospecimen Collection; Other: Electronic Health Record Review; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility of enrollment onto study
The number of participants enrolled into the study compared to trial goals.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 2 years
Representative enrollment
Meeting or exceeding the trial enrollment goals on a population basis.
Measured: 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.
Measured: Up to 1 year
Secondary outcomes (20)
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.
Measured: 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.
Measured: 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.
Measured: Up to 2 years
Contamination
Estimated as the number of participants receiving MCD testing outside the trial.
Measured: Up to 3 years
Effects of participant characteristics
Feasibility outcomes will be reported by participant demographics and cancer risk factors.
Measured: 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
Measured: 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.
Measured: Up to 2 years
Participation in standard of care screening
The proportion of participants that receive standard of care cancer screening in each arm.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 2 years
Specificity of each MCD assay
Specificity will be estimated for each MCD assay.
Measured: 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.
Measured: Up to 2 years
False positives
The number of participants with an abnormal MCD test and no cancer diagnosis.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2025
- Study start18 Jun 2025
- Primary completion31 Jan 2029 (estimated)
- Study completion30 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bladder CarcinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 24,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Scott D Ramsey, Principal investigator, Fred Hutchinson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06995898
- Sponsor's protocol ID
- NCI-2024-10793
- Other IDs
- NCI-2024-10793, CSRN1, CSRN1, CSRN1, P30CA015704, UG1CA286954
- Status last verified
- Aug 2026
- First submitted
- 29 May 2025
- Last updated
- 6 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
Publications
Guthrie KA, Anderson GL, Bell-Brown A, Cook LS, Doescher MP, Etzioni RB, Feng Z, Henderson LM, Herman J, Honda SA, James AS, Kaltman R, Kooperberg C, Krist AH, Lee CB, Lee JK, LeeVan E, Liao JC, Minasian LM, Moore KN, Nana-Sinkam P, Natale KE, Neslund-Dudas C, Ngo-Metzger Q, Ong MJC, Oshiro CES, Park Y, Patriotis C, Pinsky P, Prorok PC, Reuland DS, Ritzwoller DP, Rubinstein WS, Sakoda LC, Sayles J, Schenk JM, Shofer S, Simoff M, Toriola AT, White L, Wion ES, Wood M, Ramsey SD. The vanguard study: Assessing feasibility of conducting randomized trials of novel multi-cancer detection tests. Contemp Clin Trials. 2026 Aug 9:108418. doi: 10.1016/j.cct.2026.108418. Online ahead of print.
PubMed 42571808