Validation of DNA Methylation Markers for Universal and Site-specific Guided Cancer Detection, VANGUARD Study

Recruiting

• Conditions: Malignant Solid Neoplasm; Hematopoietic and Lymphatic System Neoplasm
• Interventions: Other: Non-Interventional Study

• Registration Number: NCT06304168
• Lead Sponsor: Mayo Clinic

Brief Summary

This study explores the potential value of a new blood test approach for early detection of cancer.

Detailed Description

PRIMARY OBJECTIVES:

I. Validate candidate universal and site-specific MDMs in DNA extracted from formalin-fixed paraffin embedded primary tumor and control specimens.

II. Test MDM-based models for detection of the top 16 most lethal human cancers using a non-invasive biological medium, specifically blood.

III. Assess feasibility for detection of cancers using urine samples to assay MDMs, RNA or protein in cell free or extra-cellular vesicles; patients may be the same or unique individuals from Aim 1 and 2.

OUTLINE: This is an observational study.

Patients undergo blood, urine, and/or residual tissue sample collection and have their medical records reviewed on study.

Study Timeline

• Study Start: 2019-05-13
• Study First Submitted: 2024-02-27
• Study First Submitted QC: 2024-03-04
• Study First Posted: 2024-03-12
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-04
• Last Update Posted: 2025-03-06
• Primary Completion: 2028-05-15
• Study Completion: 2028-05-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 6150

Inclusion Criteria

• Aim 1 Tissue

  • Cases:

    • Patient has a biopsy confirmed diagnosis of target histology
    • Tissue samples from synchronous or metachronous primary cancers may be used as long as they are clearly of a different target organ.
    • Tumors from patients with an underlying genetic disorder pre-disposing to cancer may be included as long as they are stratified from those without

  • Controls:

    • Patient does not have the diagnosis of target histology

• Aim 2 Blood

  • Cases:

    • Patient has a biopsy confirmed diagnosis of target histology or radiographic criteria that are unequivocal for diagnosis (example, meets radiographic criteria for hepatocellular carcinoma)

  • Controls:

    • Patient does not have a diagnosis of the target histology

• Aim 3 Urine

  • Cases:

    • Patient has a biopsy confirmed diagnosis of target histology or radiographic criteria that are unequivocal for diagnosis (example, meets radiographic criteria for hepatocellular carcinoma)

  • Controls:

    • Patient does not have a diagnosis of the target histology

Exclusion Criteria

• Aim 1 Tissue

  • Cases and Controls:

    • Patient has had any transplants prior to tissue collection
    • Patient has received chemotherapy class drugs within 5 years prior to tissue collection

  • Cases:

    • Patient has had radiation to the current target lesion prior to tissue collection
    • Patient has multi-centric/multi-focal breast cancer with differing genetic profiles (ER/HER2/PR status differ; if multiple masses are present and not all are tested then exclude patient)
    • Patient has bilateral breast cancer/Ductal carcinoma in situ (DCIS)

• Aim 2 Blood

  • Cases and Controls:

    • Patient has known cancer outside of the target cancer 5 years prior to blood collection (not including basal cell or squamous cell skin cancers)
    • Patient has received chemotherapy class drugs in the 5 years prior to blood collection
    • Patient has had any prior radiation therapy to the target lesion prior to blood collection
    • Patient has had a biopsy to the target organ and/or lesion within 3 days before blood collection

  • Cases:

    • Patient has had an intervention to completely remove current target pathology
    • The current target pathology is a recurrence
    • Patient has multi-centric/multi-focal breast cancer with differing genetic profiles (ER/HER2/PR status differ; if multiple masses are present and not all are tested then exclude patient)
    • Patient has bilateral breast cancer/DCIS

• Aim 3 Urine

  • Patient has known cancer outside of the target cancer 5 years prior to urine collection (not including basal cell or squamous cell skin cancers)

  • Patient has received chemotherapy class drugs in the 5 years prior to urine collection

  • Patient has had any prior radiation therapy to the target lesion prior to urine collection

  • Patient has had a biopsy to the target organ and/or lesion within 3 days before urine collection

  • The current target pathology is a recurrence

  • Patient has chronic indwelling urinary catheter

  • Patient has had a urinary tract infection within the 14 days prior to sample collection

  • If patient does not have a primary bladder, ureter or urethral cancer, patient has a history of bladder ureter, or urethral cancer

  • Cases:

    • Patient has had an intervention to completely remove current target pathology
    • The current target pathology is a recurrence
    • Patient has multi-centric/multi-focal breast cancer with differing genetic profiles [estrogen receptor (ER)/human epidermal growth factor receptor 2 (HER2)/progesterone receptor (PR)] status differ; if multiple masses are present and not all are tested then exclude patient)
    • Patient has bilateral breast cancer/DCIS

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Observational	Non-Interventional Study	Patients undergo blood, urine, and/or residual tissue sample collection and have their medical records reviewed on study.

Primary Outcome Measures

Name	Time	Method
Cancer specific site prediction - blood samples/MDM	Baseline (samples collected at enrollment)	Blood samples will be assayed for methylated DNA markers (MDMs) to identify individual organ sites of primary tumors.
Cancer specific site prediction - blood samples/RNA	Baseline (samples collected at enrollment)	Blood samples will be assayed for ribonucleic acid (RNA) to identify individual organ sites of primary tumors.
Overall cancer (Y/N) - urine test	Baseline (samples collected at enrollment)	Urine samples will be assayed for known cancer markers to explore the potential value of a new urine test approach to detecting cancer. Accuracy of results may be evaluated based on review of past, present, and future medical record information.
Cancer specific site prediction - urine samples/MDM	Baseline (samples collected at enrollment)	Urine samples will be assayed for methylated DNA markers (MDMs) to identify individual organ sites of primary tumors.
Overall cancer (Y/N) - blood test	Baseline (samples collected at enrollment)	Blood samples will be assayed for known cancer markers to explore the potential value of a new blood test approach to detecting cancer. Accuracy of results may be evaluated based on review of past, present, and future medical record information.
Cancer specific site prediction - urine samples/RNA	Baseline (samples collected at enrollment)	Urine samples will be assayed for ribonucleic acid (RNA) to identify individual organ sites of primary tumors.

Trial Locations

Locations (1)

Mayo Clinic in Rochester; 🇺🇸 Rochester, Minnesota, United States