Clinical trial NCT06995898: A Study to Evaluate Multicancer Detection (MCD) Tests and Their Impact on Participant Health and Cancer Screening, The Vanguard Study
Official title: The Vanguard Study: Testing a New Way to Screen for Cancer
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Bladder Carcinoma
Breast Carcinoma
Colorectal Carcinoma
Esophageal Carcinoma
Gastric Carcinoma
Liver Carcinoma
Lung Carcinoma
Malignant Solid Neoplasm
Ovarian Carcinoma
Pancreatic Carcinoma
Prostate Carcinoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2025-05-30
Enrollment: 24000
Sex: ALL
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

Brief summary: This clinical trial studies the impact of two multicancer detection (MCD) tests, Shield and Avantect, as cancer screening tests in a population of adults aged 45-75 without cancer in underrepresented communities. This study provides early information on how well MCD tests perform as cancer screening tools and help researchers understand how patients and their doctors make decisions about their care when the MCD test comes back with a normal (negative) or an abnormal (positive) result. The goal of cancer screening is to reduce the burden of cancer by identifying cancers before they show symptoms or signs, ideally at an early stage where the chance of cure is highest, and treatment may be less aggressive. MCD is a test that measures tumor cell biomarkers in blood in order to screen for multiple cancers simultaneously. MCDs are simple to implement for both health care providers and their patients, making them accessible even in under-resourced settings. The Avantect MCD test is a next-generation sequencing (NGS)- based screening test intended for the qualitative detection of the presence or absence of cancer-related abnormal signals in plasma cell free deoxyribonucleic acid (cfDNA) derived from whole blood. The Avantect MCD test reports on the possible presence of 8 cancers: breast, colorectal, esophagus, stomach, liver, lung, ovarian and pancreas and may indicate the presence of up to two predicted tissue of origins. The Shield MCD blood test reports cancer derived alterations associated from whole blood samples collected from individuals at average risk. The Shield MCD test is developed for the detection of cancers and the prediction of the tissue of origin of 10 cancer types: bladder, breast, colorectal, esophageal, stomach, liver, lung, ovarian, pancreatic, and prostate. Undergoing Avantect and Shield MCD testing may work better at screening participants aged 45-75 for cancer in underrepresented communities.

Detailed description: PRIMARY OBJECTIVES:

I. Assess the feasibility of recruitment and adherence to protocol-required baseline and follow-up data and blood collection. (Feasibility) II. Assess the feasibility of achieving representative enrollment across participating recruitment sites. (Feasibility)

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 on rates of standard of care screening. (Feasibility) II. To determine the timeliness of returning test results to participants. (Feasibility) III. To understand the factors contributing to lack of diagnostic resolution of an abnormal MCD test. (Feasibility) IV. To examine the effects of participant characteristics, including cancer risk factors and social determinants of health, on all aspects of feasibility. (Feasibility) V. To estimate the proportion of participants receiving an MCD test outside of the trial. (Feasibility) VI. To assess the feasibility of a staggered introduction of the second MCD assay intervention arm. (Feasibility) VII. To estimate the proportion of abnormal MCD tests that are diagnostically resolved, and the time to resolution. (Clinical Impact and Outcomes) VIII. To compare the proportion of participants who receive standard of care screening during follow-up between the intervention and control arms. (Clinical Impact and Outcomes) IX. To assess the accuracy of tissue of origin prediction for each MCD assay. (Clinical Impact and Outcomes) X. To estimate the incidence of complications related to diagnostic evaluation of an abnormal MCD test result. (Clinical Impact and Outcomes) XI. To assess the effect of an abnormal MCD test and diagnostic workup on anxiety and cancer worry. (Clinical Impact and Outcomes) XII. To evaluate the clinical diagnostic performance of the MCD assays. (Clinical Impact and Outcomes)

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 are provided results of tests and those with abnormal results 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 are provided results of tests and those with abnormal results 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 up at 1 year and then up to 10 years.

Eligibility criteria: 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
* Ongoing cancer diagnostic work-up as determined by site investigator
* Ongoing participation in another study of an investigational cancer screening test or technology
* Currently breastfeeding or pregnant, or planning to become pregnant in the next year

Primary outcomes:
measure: Feasibility of initial enrollment onto study
timeFrame: At time of enrollment
measure: Feasibility of randomization
timeFrame: At time of randomization
measure: Proportion of participants who complete baseline and follow-up questionnaires within 60 days of receipt (Feasibility)
timeFrame: Up to 1 year
measure: 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 (Feasibility)
timeFrame: Up to 1 year
measure: Proportion of participants considered lost to follow-up within 2 years of randomization (Feasibility)
timeFrame: Up to 2 years
measure: Representative enrollment (Feasibility)
timeFrame: At enrollment
measure: Staggered start of intervention arm 2 (Feasibility)
timeFrame: Up to 2 years
Secondary outcomes:
measure: Impact of participant blinding (Feasibility)
timeFrame: Up to 2 years
measure: Timely return of MCD test result (Feasibility)
timeFrame: Up to 2 years
measure: Factors contributing to lack of diagnostic resolution of an abnormal MCD test (Feasibility)
timeFrame: Up to 2 years
measure: Contamination (Feasibility)
timeFrame: Up to 2 years
measure: Effects of participant characteristics (Feasibility)
timeFrame: At time of enrollment
measure: Diagnostic resolution following an abnormal MCD test result (Clinical Impact and Outcomes)
timeFrame: Within 12 months following an abnormal MCD test result
measure: Time to diagnostic resolution (Clinical Impact and Outcomes)
timeFrame: From date of ACCESS Hub receipt of abnormal MCD test result to date of provider-reported diagnostic resolution
measure: Participation in Soc screening (Clinical Impact and Outcomes)
timeFrame: From baseline up to 2 years
measure: Accuracy of tissue of origin prediction (Clinical Impact and Outcomes)
timeFrame: Up to 2 years
measure: Complications related to diagnostic evaluation of an abnormal MCD test result (Clinical Impact and Outcomes)
timeFrame: From the time of the first diagnostic procedure until either diagnostic resolution or discontinuation of the workup
measure: Anxiety and Cancer Worry Questionnaire (Clinical Impact and Outcomes)
timeFrame: At year 1 and year 2 follow-up
measure: (Empirical) Sensitivity of clinical diagnostic performance of each MCD assay (Clinical Impact and Outcomes)
timeFrame: Up to 2 years
measure: Specificity of each MCD assay (Clinical Impact and Outcomes)
timeFrame: After 12 month follow up period
measure: Test positive rates (Clinical Impact and Outcomes)
timeFrame: Up to 2 years
measure: False positives (Clinical Impact and Outcomes)
timeFrame: Up to 2 years
measure: (Targeted cancer) Positive predictive value (PPV) (Clinical Impact and Outcomes)
timeFrame: Up to 2 years
measure: (All cancer) PPV (Clinical Impact and Outcomes)
timeFrame: Up to 2 years
measure: Interval cancers (Clinical Impact and Outcomes)
timeFrame: Up to 2 years
measure: Detected cancers (Clinical Impact and Outcomes)
timeFrame: Up to 2 years
measure: (Targeted cancer) Negative predictive value (Clinical Impact and Outcomes)
timeFrame: Up to 2 years
Other outcomes:
measure: Date of Diagnosis
timeFrame: Up to 12 years
measure: Cancer site
timeFrame: Up to 12 years
measure: Cancer stage
timeFrame: Up to 12 years
measure: Early and late stages cancer diagnosis
timeFrame: Up to 12 years
measure: Diagnosis modality
timeFrame: Up to 12 years
measure: Targeted cancer-specific mortality of each MCD assay
timeFrame: Up 2 years
measure: Cancer-specific mortality
timeFrame: Up to 12 years
measure: All-cause mortality
timeFrame: Up to 12 years
Locations:
Study officials:
affiliation: Fred Hutchinson Cancer Center
name: Scott D Ramsey
role: PRINCIPAL_INVESTIGATOR
References: