ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation

Recruiting

• Conditions: Bladder Carcinoma; Ureter Carcinoma; Renal Pelvis Carcinoma; Non-small Cell Lung Cancer; Invasive Breast Carcinoma; Cutaneous Melanoma; Esophageal Carcinoma; Gastroesophageal Junction Carcinoma; Gastric Adenocarcinoma; Pancreatic Adenocarcinoma
• Interventions: Diagnostic Test: Guardant Reveal

• Registration Number: NCT05059444
• Lead Sponsor: Guardant Health, Inc.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-09-07
• Study First Submitted: 2021-09-16
• Study First Submitted QC: 2021-09-17
• Study First Posted: 2021-09-28
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-04
• Last Update Posted: 2024-12-09
• Primary Completion: 2028-02
• Study Completion: 2028-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1050

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 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

Exploratory Cohorts

• 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 stage IC-III or stage I that has high grade (grade 3-4) or clear cell histology),
• Cohort 10: High-risk endometrial carcinoma (Defined as having any of the following: serous or clear cell adenocarcinoma histology (any stage), grade 3 or 4 deeply invasive (T1b or greater) endometrioid carcinoma, stage III disease (any histology)),
• 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),
• 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)
• Is participating in a clinical trial or another observational study that is evaluating the performance of another genomic test in the post-treatment surveillance setting at predicting/detecting recurrence

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Cohort 3: Invasive breast carcinoma with all of the following:	Guardant Reveal	* Clinical stage T1-4/N0-3/M0 at presentation AND * Completed preoperative systemic chemotherapy-containing regimen AND * Underwent definitive surgical resection of the primary tumor AND * Has pathological evidence of residual invasive carcinoma in the breast and/or axillary lymph nodes AND * Hormone receptor and HER2 status are known
Cohort 5: Esophageal or gastroesophageal junction carcinoma (stage II-III)	Guardant Reveal	-
Cohort 9: High-risk epithelial ovarian or Fallopian tube carcinoma	Guardant Reveal	Defined as stage IC-III or stage I that has high grade (grade 3-4) or clear cell histology).
Cohort 1: Muscle invasive carcinoma of the bladder, ureter, or renal pelvis (stage II-III)	Guardant Reveal	-
Cohort 2: Non-small cell lung cancer (stage II-III)	Guardant Reveal	-
Cohort 6: Gastric adenocarcinoma (stage II-III)	Guardant Reveal	-
Cohort 7: Surgically resected pancreatic adenocarcinoma	Guardant Reveal	-
Cohort 8: Invasive squamous cell carcinoma of the head and neck	Guardant Reveal	Includes stage I-III oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, nasal cavity, paranasal sinus, and salivary gland cancers.
Cohort 10: High-risk endometrial carcinoma	Guardant Reveal	Defined as having any of the following: serous or clear cell adenocarcinoma histology (any stage), grade 3 or 4 deeply invasive (T1b or greater) endometrioid carcinoma, stage III disease (any histology).
Cohort 11: High-risk renal cell carcinoma	Guardant Reveal	Defined as high grade (grade 3-4) stage II, stage III or limited (resectable) stage IV treated with curative intent.
Cohort 4: Stage IIb-III cutaneous melanoma or limited (resectable) stage IV melanoma	Guardant Reveal	-

Primary Outcome Measures

Name	Time	Method
Distant Recurrence Free Interval (D-RFi)	6 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 Outcome Measures

Name	Time	Method
Sensitivity	6 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.
Positive Predictive Value	6 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).
Lead Time	6 years	Lead time defined as the interval between ctDNA detection and clinical detection of recurrence.

Trial Locations

Locations (57)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Hoag Memorial Hospital Presbyterian; 🇺🇸 Newport Beach, California, United States

The Oncology Institute of Hope & Innovation; 🇺🇸 Lakeland, Florida, United States

Tulane Cancer Center; 🇺🇸 New Orleans, Louisiana, United States

Ironwood Cancer & Research Centers; 🇺🇸 Chandler, Arizona, United States

Genesis Cancer Center; 🇺🇸 Hot Springs, Arkansas, United States

University of California, San Diego; 🇺🇸 La Jolla, California, United States

Memorial Healthcare System; 🇺🇸 Hollywood, Florida, United States

Sutter Institute for Medical Research; 🇺🇸 Sacramento, California, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

University of Colorado; 🇺🇸 Aurora, Colorado, United States

Christus Highland/ Boniol; 🇺🇸 Shreveport, Louisiana, United States

Central Maine Medical Center; 🇺🇸 Lewiston, Maine, United States

Mayo Clinic (Rochester); 🇺🇸 Rochester, Minnesota, United States

Astera Cancer Care; 🇺🇸 East Brunswick, New Jersey, United States

Icahn School of Medicine at Mount Sinai; 🇺🇸 New York, New York, United States

UNC- Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States

Cancer & Hematology Centers of Western Michigan; 🇺🇸 Grand Rapids, Michigan, United States

Toledo Clinic Cancer Center; 🇺🇸 Toledo, Ohio, United States

Crozer-Keystone Health System; 🇺🇸 Broomall, Pennsylvania, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

The Christ Hospital Cancer Center; 🇺🇸 Cincinnati, Ohio, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Cancer Care Associates of York; 🇺🇸 York, Pennsylvania, United States

Carolina Urologic Research Center; 🇺🇸 Myrtle Beach, South Carolina, United States

Carolina Blood and Cancer Care Associates; 🇺🇸 Rock Hill, South Carolina, United States

UT Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

DHR Health Advance Care Center; 🇺🇸 Edinburg, Texas, United States

The Center for Cancer and Blood Disorders; 🇺🇸 Fort Worth, Texas, United States

The University of Texas Health Science Center at San Antonio; 🇺🇸 San Antonio, Texas, United States

Utah Cancer Specialists; 🇺🇸 Salt Lake City, Utah, United States

ThedaCare Regional Cancer Center; 🇺🇸 Appleton, Wisconsin, United States

CHU Besançon; 🇫🇷 Besançon, France

Hôpital Franco-Britannique; 🇫🇷 Levallois-Perret, France

Institut Paoli-Calmettes; 🇫🇷 Marseille, France

Ambroise Paré-Hartmann; 🇫🇷 Neuilly, France

APHP Tenon Hospital - Sorbonne; 🇫🇷 Paris, France

Asklepios Klinik Altona; 🇩🇪 Hamburg, Germany

SLK-Kliniken Heilbronn GmbH; 🇩🇪 Heilbronn, Germany

Ludwig Maximilian University Munich; 🇩🇪 Munich, Germany

Instituto Romagnolo per lo Studio dei Tumori "Dino Amadori" IRCCS IRST, SrL; 🇮🇹 Meldola, Italy

Azienda USL-IRCCS di Reggio Emilia; 🇮🇹 Reggio Emilia, Italy

Policlinico Universitario Agostino Gemelli; 🇮🇹 Roma, Italy

Hospital Teresa Herrera (C.H.U.A.C); 🇪🇸 A Coruña, Spain

Vall Hebron Institute of Oncology; 🇪🇸 Barcelona, Spain

Hospital Clinic of Barcelona; 🇪🇸 Barcelona, Spain

ICO Institut Catala d'Oncologia; 🇪🇸 Barcelona, Spain

Instituto Catalan de Oncologia de Girona; 🇪🇸 Girona, Spain

Hospital Universitario Insular de Gran Canaria; 🇪🇸 Las Palmas De Gran Canaria, Spain

Hospital San Carlos; 🇪🇸 Madrid, Spain

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain

CIOSS HM Sanchinarro; 🇪🇸 Madrid, Spain

Hospital Universitario Virgen de la Victoria; 🇪🇸 Málaga, Spain

CCS Hospital Universitari Parc Taulí; 🇪🇸 Sabadell, Spain

Hospital Clinico de Santiago de Compostela; 🇪🇸 Santiago De Compostela, Spain

Hospital Clínico de Valencia; 🇪🇸 Valencia, Spain

Redwood City; 🇺🇸 Redwood City, California, United States