ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation (ORACLE)

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.

Study Overview

• Status: Recruiting
• Conditions: Renal Cell Carcinoma; Pancreatic Adenocarcinoma; Gastric Adenocarcinoma; Squamous Cell Carcinoma of the Head and Neck; Non-small Cell Lung Cancer; Fallopian Tube Carcinoma; Endometrial Carcinoma; Bladder Carcinoma; Esophageal Carcinoma; Invasive Breast Carcinoma; Cutaneous Melanoma; Rectal Adenocarcinoma; Epithelial Ovarian Carcinoma; Gastroesophageal Junction Carcinoma; Ureter Carcinoma; Renal Pelvis Carcinoma
• Intervention / Treatment: Diagnostic test: Guardant Reveal

• Study Type: Observational
• Enrollment (Estimated): 2020

Contacts and Locations

• Study Contact: Name: Clinical Trial Operations; Phone Number: 8556988887; Email: mrdoraclestudy@guardanthealth.com

Study Locations

• France
  • Besançon, France, 25000
    • Recruiting
    • CHU Besançon
    • Contact: Christine Guglielmetti-Bargot
  • Levallois-Perret, France, 92300
    • Recruiting
    • Hôpital Franco-Britannique
    • Contact: Hajar Eddahbi
  • Marseille, France, 13009
    • Recruiting
    • Institut Paoli-Calmettes
    • Contact: Sameh Bou Ali
  • Neuilly, France, 92200
    • Recruiting
    • Ambroise Paré-Hartmann
    • Contact: Messaouda Merzoug
  • Paris, France, 75020
    • Recruiting
    • APHP Tenon Hospital - Sorbonne
    • Contact: Hakima Manseur
• Germany
  • Hamburg, Germany, 22763
    • Recruiting
    • Asklepios Klinik Altona
    • Contact: Dirk Arnold
  • Heilbronn, Germany, 74078
    • Recruiting
    • SLK-Kliniken Heilbronn GmbH
    • Contact: Josef Huber
  • Munich, Germany, 81377
    • Recruiting
    • Ludwig Maximilian University Munich
    • Contact: C. Benedikt Westphalen
• Italy
  • Meldola, Italy, 47014
    • Recruiting
    • Instituto Romagnolo per lo Studio dei Tumori "Dino Amadori" IRCCS IRST, SrL
    • Contact: Emanuela Montanari
  • Reggio Emilia, Italy, 42123
    • Recruiting
    • Azienda USL-IRCCS di Reggio Emilia
    • Contact: Erika Gervasi
  • Roma, Italy, 00168
    • Recruiting
    • Policlinico Universitario Agostino Gemelli
    • Contact: Ilenia Marino
• Spain
  • A Coruña, Spain, 15006
    • Recruiting
    • Hospital Teresa Herrera (C.H.U.A.C)
    • Contact: Sabela Varela Rodriguez
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clinic of Barcelona
    • Contact: Debora Moreno Fernandez
  • Barcelona, Spain, 08035
    • Recruiting
    • Vall Hebron Institute of Oncology
    • Contact: Pol Sisó Camarasa
  • Barcelona, Spain, 08908
    • Recruiting
    • ICO Institut Catala d'Oncologia
    • Contact: Ana Rosa Garcia Oliva
  • Girona, Spain, 17007
    • Recruiting
    • Instituto Catalan de Oncologia de Girona
    • Contact: Begona Martin
  • Las Palmas De Gran Canaria, Spain
    • Recruiting
    • Hospital Universitario Insular de Gran Canaria
    • Contact: Sara Suárez Guerra
  • Madrid, Spain, 28046
    • Recruiting
    • Hospital Universitario La Paz
    • Contact: Claudia Morrugares Portero
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital San Carlos
    • Contact: Raquel Rodriguez
  • Madrid, Spain, 28050
    • Recruiting
    • CIOSS HM Sanchinarro
    • Contact: Begoña Martinez Montesino
  • Málaga, Spain, 29010
    • Recruiting
    • Hospital Universitario Virgen de la Victoria
    • Contact: Juan Manuel Escandell
  • Sabadell, Spain, 08208
    • Recruiting
    • CCS Hospital Universitari Parc Taulí
    • Contact: Jose Garcia Ruiz
  • Santiago De Compostela, Spain, 15706
    • Recruiting
    • Hospital Clínico de Santiago de Compostela
    • Contact: Iria Portos
  • Valencia, Spain, 46010
    • Recruiting
    • Hospital Clinico de Valencia
    • Contact: Matteo Stocco
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Recruiting
      • University of Alabama at Birmingham
      • Contact: Susan Binkley
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Recruiting
      • Ironwood Cancer & Research Centers
      • Contact: Sarah Shilling
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • Terminated
      • Genesis Cancer Center
  • California
    • La Jolla, California, United States, 92093
      • Recruiting
      • University of California, San Diego
      • Contact: Susanna Lee
    • Newport Beach, California, United States, 92663
      • Recruiting
      • Hoag Memorial Hospital Presbyterian
      • Contact: Alexandra Clark
    • Redwood City, California, United States, 94063
      • Recruiting
      • Redwood City
      • Contact: Clinical Trial Operations
    • Sacramento, California, United States, 95816
      • Terminated
      • Sutter Institute for Medical Research
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado
      • Contact: Emily Harper
  • Florida
    • Hollywood, Florida, United States, 33021
      • Recruiting
      • Memorial Healthcare System
      • Contact: Machelle Seymour
    • Lakeland, Florida, United States, 33812
      • Recruiting
      • The Oncology Institute of Hope & Innovation
      • Contact: Shanna Kennedy
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Recruiting
      • Tulane Cancer Center
      • Contact: Alex Lieberman
    • Shreveport, Louisiana, United States, 71105
      • Recruiting
      • Christus Highland/ Boniol
      • Contact: Nancy Hassan
  • Maine
    • Lewiston, Maine, United States, 04240
      • Recruiting
      • Central Maine Medical Center
      • Contact: Jessica Bolduc
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Terminated
      • Massachusetts General Hospital
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Recruiting
      • Cancer & Hematology Centers of Western Michigan
      • Contact: Angela Newman
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic (Rochester)
      • Contact: Renee Bradshaw
  • New Jersey
    • East Brunswick, New Jersey, United States, 08816
      • Recruiting
      • Astera Cancer Care
      • Contact: Percy Yeung
  • New York
    • New York, New York, United States, 10029
      • Terminated
      • Icahn School of Medicine at Mount Sinai
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Recruiting
      • UNC- Chapel Hill
      • Contact: Chris Hilliiard
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Terminated
      • The Christ Hospital Cancer Center
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
      • Contact: Maria Clark
    • Toledo, Ohio, United States, 43623
      • Recruiting
      • Toledo Clinic Cancer Center
      • Contact: Jennifer Martinez
  • Pennsylvania
    • Broomall, Pennsylvania, United States, 19008
      • Terminated
      • Crozer-Keystone Health System
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
      • Contact: Willdragon Wang
    • York, Pennsylvania, United States, 17403
      • Recruiting
      • Cancer Care Associates of York
      • Contact: Katelyn Bean
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Recruiting
      • Carolina Urologic Research Center
      • Contact: Angela Buffkin
    • Rock Hill, South Carolina, United States, 29732
      • Recruiting
      • Carolina Blood and Cancer Care Associates
      • Contact: Carson Lee Gallo
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • UT Southwestern Medical Center
      • Contact: Saketh Nadimpalli
    • Edinburg, Texas, United States, 78539
      • Recruiting
      • DHR Health Advance Care Center
      • Contact: Edgar Lopez Pacheco
    • Forth Worth, Texas, United States, 76104
      • Recruiting
      • The Center for Cancer and Blood Disorders
      • Contact: Anna Rose Abangan
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • The University of Texas Health Science Center at San Antonio
      • Contact: James Denno
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Recruiting
      • Utah Cancer Specialists
      • Contact: Angela Nuttall
  • Wisconsin
    • Appleton, Wisconsin, United States, 54911
      • Recruiting
      • ThedaCare Regional Cancer Center
      • Contact: Rachel Luedtke

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The primary study population will include participants with invasive bladder/upper urinary tract carcinoma, NSCLC, breast cancer, cutaneous melanoma, esophageal carcinoma, gastroesophageal junction carcinoma, gastric adenocarcinoma, pancreatic adenocarcinoma, squamous cell carcinoma of the head and neck, epithelial ovarian/Fallopian tube carcinoma, endometrial cancer, and renal cell carcinoma (RCC) as per inclusion/exclusion criteria below. Participants with rectal adenocarcinoma undergoing pre-operative systemic chemotherapy/chemoradiotherapy- or immunotherapy-containing regimen are included as an exploratory cohort as per inclusion/exclusion criteria below. Inclusion criteria were selected to enroll participants who are predicted to have >15-20% risk of recurrence within 3 years in order to sufficiently power the study for recurrence events.

Description

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 5 years as outlined in the study protocol and informed consent AND
• Have at least one Landmark blood sample

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: Invasive squamous cell carcinoma of the head and neck (Includes stage I-IVB oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, nasal cavity, and paranasal sinus cancers),
• Cohort 9: High-risk epithelial ovarian or Fallopian tube carcinoma (Defined as FIGO stage IC-III or stage IA-IB that has high grade or clear cell histology),
• Cohort 10: High-risk endometrial carcinoma (Defined as 2023 FIGO Stage II-III),
• Cohort 11: High-risk renal cell carcinoma (Defined as high grade (grade 3-4) stage II, stage III or limited (resectable) stage IV treated with curative intent)

Exploratory Cohort

• Cohort 12: 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

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, 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)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

12

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort 1: Muscle invasive carcinoma of the bladder, ureter, or renal pelvis (stage II-III)	Diagnostic test: Guardant Reveal; Guardant Reveal is a minimal residual disease (MRD) panel for use in recurrence detection of early-stage solid tumors.
Cohort 5: Esophageal or gastroesophageal junction carcinoma (stage II-III)	Diagnostic test: Guardant Reveal; Guardant Reveal is a minimal residual disease (MRD) panel for use in recurrence detection of early-stage solid tumors.
Cohort 6: Gastric adenocarcinoma (stage II-III)	Diagnostic test: Guardant Reveal; Guardant Reveal is a minimal residual disease (MRD) panel for use in recurrence detection of early-stage solid tumors.
Cohort 11: High-risk renal cell carcinoma; Defined as high grade (grade 3-4) stage II, stage III or limited (resectable) stage IV treated with curative intent.	Diagnostic test: Guardant Reveal; Guardant Reveal is a minimal residual disease (MRD) panel for use in recurrence detection of early-stage solid tumors.
Cohort 3: Invasive breast carcinoma with hormone receptor and HER2 status; Cohort 3A: High-risk HER2+ breast cancer (any ER, PR status allowed); defined as having stage II-III or having residual invasive disease (i.e. non-pathologic complete response) following a neoadjuvant chemotherapy-containing regimen OR Cohort 3B: High-risk triple negative breast cancer (TNBC); defined as having stage II-III or having residual invasive disease (i.e. non-pathologic complete response) following a neoadjuvant chemotherapy-containing regimen OR Cohort 3C: HR-positive/HER2-negative invasive breast carcinoma with either >4 positive axillary lymph nodes or 1-3 positive axillary lymph nodes and at least one of the following: tumor size >5 cm, histologic grade 3, or validated gene expression assay indicating high recurrence risk (OncotypeDx score > 26, MammaPrint high, ProSigna high, EndoPredict high)	Diagnostic test: Guardant Reveal; Guardant Reveal is a minimal residual disease (MRD) panel for use in recurrence detection of early-stage solid tumors.
Cohort 4: Stage IIB-III cutaneous melanoma or limited (resectable) stage IV melanoma	Diagnostic test: Guardant Reveal; Guardant Reveal is a minimal residual disease (MRD) panel for use in recurrence detection of early-stage solid tumors.
Cohort 7: Pancreatic adenocarcinoma; That is has been surgically resected or is eligible for surgical resection	Diagnostic test: Guardant Reveal; Guardant Reveal is a minimal residual disease (MRD) panel for use in recurrence detection of early-stage solid tumors.
Cohort 8: Invasive squamous cell carcinoma of the head and neck; Includes stage I-IVB oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, nasal cavity, or paranasal sinus	Diagnostic test: Guardant Reveal; Guardant Reveal is a minimal residual disease (MRD) panel for use in recurrence detection of early-stage solid tumors.
Cohort 12: 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
Cohort 2: Non-small cell lung cancer (stage IB-III); Cohort 2A: Resectable Cohort 2B: Unresectable	Diagnostic test: Guardant Reveal; Guardant Reveal is a minimal residual disease (MRD) panel for use in recurrence detection of early-stage solid tumors.
Cohort 9: High-risk epithelial ovarian or Fallopian tube carcinoma; Defined as FIGO stage IC-III or stage IA-IB that has high grade or clear cell histology.	Diagnostic test: Guardant Reveal; Guardant Reveal is a minimal residual disease (MRD) panel for use in recurrence detection of early-stage solid tumors.
Cohort 10: High-risk endometrial carcinoma; Defined as FIGO stage II-III.	Diagnostic test: Guardant Reveal; Guardant Reveal is a minimal residual disease (MRD) panel for use in recurrence detection of early-stage solid tumors.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distant Recurrence Free Interval (D-RFi)	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.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity	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.	3 years
Positive Predictive Value	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 years
Lead Time	Lead time defined as the interval between ctDNA detection and clinical detection of recurrence.	3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence-free interval (RFi)	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.	3 years
Negative predictive value (NPV)	Negative predictive value (NPV) defined as the proportion of participants who have ctDNA not detected who have no evidence of recurrence.	3 years
Association with resolution of indeterminate findings	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 years
Sensitivity for local recurrence	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.	3 years
Index Cancer-Specific Survival (ICSS)	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.	3 years
Overall Survival (OS)	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.	3 years
Rate of ctDNA clearance with adjuvant chemotherapy	Rate of ctDNA clearance with adjuvant chemotherapy defined as the proportion of patients who have ctDNA detected at the pre-enrollment timepoint whose ctDNA becomes undetectable at the Landmark timepoint.	3 years
Association of ctDNA detection status with pathologic response		3 years

Collaborators and Investigators

• Sponsor: Guardant Health, Inc.
• Investigators: Study Director: Study Director, Guardant Health, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2021
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2029

Study Registration Dates

• First Submitted: September 16, 2021
• First Submitted That Met QC Criteria: September 17, 2021
• First Posted (Actual): September 28, 2021

Study Record Updates

• Last Update Posted (Actual): August 22, 2025
• Last Update Submitted That Met QC Criteria: August 18, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Uterine Diseases; Genital Diseases, Female; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Neoplastic Processes; Esophageal Diseases; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Skin Diseases; Breast Diseases; Urologic Neoplasms; Uterine Neoplasms; Urinary Bladder Diseases; Carcinoma, Squamous Cell; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Squamous Cell Carcinoma of Head and Neck; Carcinoma; Neoplasm, Residual; Esophageal Neoplasms; Breast Neoplasms; Adenocarcinoma; Urinary Bladder Neoplasms; Endometrial Neoplasms
• Other Study ID Numbers: 02-MX-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No