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; Epithelial Ovarian Carcinoma; Gastroesophageal Junction Carcinoma; Ureter Carcinoma; Renal Pelvis Carcinoma
• Intervention / Treatment: Diagnostic test: Guardant Reveal

• Study Type: Observational
• Enrollment (Anticipated): 1000

Contacts and Locations

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

Study Locations

• United States
  • California
    • Redwood City, California, United States, 94063
      • Recruiting
      • Redwood City
      • Contact: Clinical Trial Operations

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

The primary study population will include participants with invasive bladder, ureteral, or renal pelvis carcinoma, NSCLC, or breast cancer with residual invasive disease following neoadjuvant chemotherapy as per inclusion/exclusion criteria defined. Exploratory cohorts include participants with 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. Approximately 1,000 total patients will be enrolled into the study.

Description

Inclusion Criteria:

• Age > 18 years old AND
• Were treated with curative 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 blood sample collected 4-12 weeks after completion of primary treatment of the Index Cancer
• Have a histologically confirmed Index Cancer that qualifies for inclusion, defined as:

Primary Study Cohorts

• Cohort 1: Muscle invasive carcinoma of the bladder, ureter, or renal pelvis (stage II-III),
• Cohort 2: Non-small cell lung cancer (stage II-III),
• Cohort 3: Invasive breast carcinoma with all of the following:

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

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: Surgically resected pancreatic adenocarcinoma,
• Cohort 8: Invasive squamous cell carcinoma of the head and neck (includes stage I-III oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, nasal cavity, paranasal sinus, and salivary gland 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)

Exclusion Criteria:

• History of allogeneic organ or tissue transplant
• Index cancer has neuroendocrine histology
• History of another primary cancer, with the exception of the following (if adequately treated and the patient is without evidence of disease at the time of enrollment): in situ cancers, non-melanoma skin carcinoma, localized low-risk prostate cancer (Gleason score < 6) with PSA in the normal range, and stage I papillary thyroid carcinoma.
• 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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

11

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 2: Non-small cell lung cancer (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 3: Invasive breast carcinoma with all of the following: 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	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 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 7: Surgically resected pancreatic adenocarcinoma	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-III oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, nasal cavity, paranasal sinus, and salivary gland cancers.	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 stage IC-III or stage I that has high grade (grade 3-4) 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 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).	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.

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.	6 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.	6 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).	6 years
Lead Time	Lead time defined as the interval between ctDNA detection and clinical detection of recurrence.	6 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.	6 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.	6 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.	6 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.	6 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.	6 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.	6 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.	6 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 (Anticipated): February 1, 2028
• Study Completion (Anticipated): February 1, 2028

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): September 9, 2022
• Last Update Submitted That Met QC Criteria: September 7, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No