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NCT Number: NCT05059444

ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation

The purpose of ORACLE is to demonstrate the ability of a novel ctDNA assay developed by Guardant Health to detect recurrence in individuals treated for early-stage solid tumors. It is necessary that ctDNA test results are linked to clinical outcomes in order to demonstrate clinical validity for recurrence detection and explore its value in a healthcare environment subject to cost containment.

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Key information

Conditions

Bladder Carcinoma Adenocarcinoma Adnexal Diseases Bronchial Neoplasms Carcinoma Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Carcinoma, Ovarian Epithelial Carcinoma, Renal Cell Carcinoma, Squamous Cell Colon Adenocarcinoma Colonic Diseases Colonic Neoplasms Colorectal Neoplasms Cutaneous Melanoma Digestive System Diseases Digestive System Neoplasms Endocrine Gland Neoplasms Endocrine System Diseases Endometrial Carcinoma Endometrial Neoplasms Epithelial Ovarian Carcinoma Esophageal Carcinoma Esophageal Diseases Esophageal Neoplasms Fallopian Tube Carcinoma Fallopian Tube Diseases Fallopian Tube Neoplasms Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Gastric Adenocarcinoma Gastroesophageal Junction Carcinoma Gastrointestinal Diseases Gastrointestinal Neoplasms Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Gonadal Disorders Head and Neck Neoplasms Intestinal Diseases Intestinal Neoplasms Invasive Breast Carcinoma Kidney Diseases Kidney Neoplasms Lung Diseases Lung Neoplasms Male Urogenital Diseases Melanoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Non-small Cell Lung Cancer Ovarian Diseases Ovarian Neoplasms Pancreatic Adenocarcinoma Rectal Adenocarcinoma Rectal Diseases Rectal Neoplasms Renal Cell Carcinoma Renal Pelvis Carcinoma Respiratory Tract Diseases Respiratory Tract Neoplasms Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases Squamous Cell Carcinoma of Head and Neck Squamous Cell Carcinoma of the Head and Neck Thoracic Neoplasms Ureter Carcinoma Ureteral Diseases Ureteral Neoplasms Urinary Bladder Diseases Urinary Bladder Neoplasms Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms Uterine Diseases Uterine Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

CHU Besançon, Besançon, France

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age > 18 years old AND
  • Initial treatment is given with curative/radical intent AND
  • Are planning to undergo regular follow-up and monitoring for cancer recurrence per standard of care at the enrolling site AND
  • Provided written informed consent to participate in the study AND
  • Are willing to have de-identified clinical data shared with investigators at regular intervals as outlined in the study protocol and informed consent AND
  • Are willing to provide blood samples at enrollment and at subsequent clinical visits coinciding with standard of care follow-up, for up to 3 years as outlined in the study protocol and informed consent AND
  • Have at least one Landmark blood sample collected. Landmark samples are collected 3-12 weeks after surgery, chemotherapy and/or radiation/chemoradiation as applicable based on the participant's planned treatment regimen
  • Have a histologically confirmed Index Cancer that qualifies for inclusion, defined as:

Primary Study Cohorts

  • Cohort 1: Cohort 1: Muscle invasive carcinoma of the bladder, ureter, or renal pelvis (stage II-III),
  • Cohort 2: Cohort 2: Non-small cell lung cancer (stage IB-III):

Cohort 2A: Resectable OR Cohort 2B: Unresectable,

  • Cohort 3: Invasive breast carcinoma with hormone receptor (e.g. estrogen receptor (ER) and progesterone receptor (PR) expression) and human epidermal growth factor receptor 2 (HER2) status known and one the following:

Cohort 3A: High-risk2 HER2+ breast cancer (any ER, PR status allowed) OR Cohort 3B: High-risk2 triple negative breast cancer (TNBC) OR Cohort 3C: High-risk3 HR-positive/HER2-negative invasive breast carcinoma,

  • Cohort 4: Stage IIB-III cutaneous melanoma or limited (resectable) stage IV melanoma treated with curative intent,
  • Cohort 5: Esophageal or gastroesophageal junction carcinoma (stage II-III),
  • Cohort 6: Gastric adenocarcinoma (stage II-III),
  • Cohort 7: Pancreatic adenocarcinoma that is has been surgically resected or is eligible for surgical resection,
  • Cohort 8: Cohort 8: Invasive squamous cell carcinoma of the head and neck (includes stage I-IVB HPV-negative or stage III-IVB HPV-positive oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, nasal cavity, or paranasal sinus),
  • Cohort 9: High-risk epithelial ovarian or Fallopian tube carcinoma (defined as FIGO stage IC-III, stage IA-IB that has high grade, carcinosarcoma, or clear cell histology),
  • Cohort 10: Endometrial carcinoma (2023 FIGO Stage II-III or 2023 FIGO Stage IC or any Stage I with p53 abnormal molecular subtype),
  • Cohort 11: High-risk renal cell carcinoma (Defined as high grade (grade 3-4) stage II, stage III or limited stage IV (meaning metastatic sites are considered treatable with curative intent)
  • Cohort 12: Colorectal adenocarcinoma Cohort 12A: Pathologically confirmed adenocarcinoma of the rectum (located up to 15 cm from the anal verge) that is undergoing or underwent a preoperative chemotherapy-or immunotherapy- containing regimen OR Cohort 12B: Colon adenocarcinoma (stage II-III)

Exclusion criteria

  • History of allogeneic organ or tissue transplant
  • Index cancer has predominantly neuroendocrine histology
  • History of another primary cancer diagnosed within 3 years of enrollment, with the exception that in situ cancers, non-melanoma skin carcinomas, localized low- or intermediate risk prostate cancers (defined as cancers confined to the prostate with Gleason score of 7 or lower and prostate-specific antigen (PSA) of less than 20), and stage I papillary thyroid carcinoma, and participants with bilateral/multifocal tumors within the same organ (for example, bilateral breast cancer) are allowed if diagnosed within 3 years of enrollment
  • Known distant metastasis at time of enrollment (with the exception of participants with limited/resectable stage IV cutaneous melanoma or RCC)

Treatment and study plan

Guardant Reveal

Diagnostic Test

Guardant Reveal is a minimal residual disease (MRD) panel for use in recurrence detection of early-stage solid tumors.

Primary outcomes

  1. Distant Recurrence Free Interval (D-RFi)

    Time frame: 3 years

    The primary endpoint, distant recurrence-free interval (D-RFi), will be evaluated for each of the primary study cohorts. D-RFi is defined as the time from the end of primary treatment until the time of diagnosis of a distant recurrence of the Index Cancer. Subjects without a distant recurrence will be censored at the time of last follow-up of their Index Cancer.

Secondary outcomes

  1. Sensitivity

    Time frame: 3 years

    Sensitivity defined as the proportion of participants who develop distant recurrence who have ctDNA detected at or before the time of clinical detection of recurrence.

  2. Positive Predictive Value

    Time frame: 3 years

    Positive predictive value (PPV) defined as the proportion of participants who have ctDNA detected at the landmark or any surveillance timepoint who recur (either distally or locally).

  3. Lead Time

    Time frame: 3 years

    Lead time defined as the interval between ctDNA detection and clinical detection of recurrence.

  4. Specificity

    Time frame: 3 years

    Specificity defined as the proportion of participants who are recurrence-free who have ctDNA not detected.

  5. Negative Predictive Value

    Time frame: 3 years

    Negative predictive value (NPV) defined as the proportion of participants who have ctDNA not detected at the Landmark or any surveillance timepoint who do not recur.

Other outcomes

  1. Recurrence-free interval (RFi)

    Time frame: 3 years

    Recurrence-free interval (RFi) defined as the time from the end of primary treatment until the appearance/occurrence of any recurrence (distant, regional, and/or local) of the Index Cancer. Subjects without recurrence will be censored at the time of last follow-up of their Index Cancer.

  2. Association with resolution of indeterminate findings

    Time frame: 3 years

    • The proportion of individuals whose indeterminate finding is ultimately confirmed to be disease recurrence who have ctDNA detected at the initial time the indeterminate finding is identified and
    • The proportion of ctDNA not detected participants whose indeterminate findings is ultimately confirmed to be benign.

  3. Sensitivity for local recurrence

    Time frame: 3 years

    Sensitivity for local recurrence defined as the proportion of participants who have localized recurrence (e.g., in the absence of distant metastasis) who have ctDNA detected at or before the time of clinical detection of a localized recurrence; using landmark and serial timepoints.

  4. Index Cancer-Specific Survival (ICSS)

    Time frame: 3 years

    Index Cancer-Specific Survival (ICSS) defined as the time from the date of diagnosis until the date of death from the subject's Index Cancer. Subjects who are still alive at the end of the study observation period will be censored at the time of last known vital status.

  5. Overall Survival (OS)

    Time frame: 3 years

    Overall Survival (OS) defined as the time from the date of diagnosis until the date of death from any cause. Subjects who are still alive at the end of the study observation period will be censored at the time of last known vital status.

  6. Rate of ctDNA clearance with therapy

    Time frame: 3 years

    Rate of ctDNA clearance with therapy defined as the proportion of patients who have ctDNA detected at a timepoint before starting a new therapy whose ctDNA becomes undetectable at a subsequent timepoint.

  7. Association of ctDNA detection status with pathologic response

    Time frame: 3 years

    Association of ctDNA detection status with pathologic response defined as the rate of ctDNA detection in individuals with residual invasive cancer in the resected specimen (as well as be residual cancer burden scores, where applicable), and in those with a complete pathologic response (defined as no invasive cancer detectable in the resection specimens) following neoadjuvant systemic therapy.

  8. Association of genomic/epigenomic profiles with patient outcomes

    Time frame: 3 years

    Association of genomic/epigenomic profiles with patient outcomes defined as the association between integrated genomic profiles (e.g., somatic mutations, copy number changes, tumor mutation burden etc) and epigenomic profiles (e.g., promoter methylation etc) with patient outcomes will be explored to determine if specific signatures define molecular subtypes with distinct recurrence rate/patterns, response to treatment, and/or longitudinal evolution of the tumor.

Study contacts

Contact information is provided by the study sponsor or research team.

Clinical Trial Operations

CONTACT

[email protected]

8556988887

Sponsors and collaborators

Lead sponsor

Guardant Health, Inc.

Industry

Registry information

Acronym: ORACLE

Important dates

Study start
2021
Primary completion
2030
Study completion
2030
First posted
Sep 28, 2021
Registry last updated
Sep 14, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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