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

• ClinicalTrials.gov Identifier: NCT05059444
• Recruitment Status: Recruiting
• First Posted: September 28, 2021
• Last Update Posted: September 9, 2022
• Sponsor: Guardant Health, Inc.
• Information provided by (Responsible Party): Guardant Health, Inc.

Tracking Information

• First Submitted Date: September 16, 2021
• First Posted Date: September 28, 2021
• Last Update Posted Date: September 9, 2022
• Actual Study Start Date: September 7, 2021
• Estimated Primary Completion Date: February 2028 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 17, 2021)

Distant Recurrence Free Interval (D-RFi) [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 17, 2021)

• Sensitivity [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 6 years ]
  Lead time defined as the interval between ctDNA detection and clinical detection of recurrence.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: September 17, 2021)

• Recurrence-free interval (RFi) [ Time Frame: 6 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.
• Negative predictive value (NPV) [ Time Frame: 6 years ]
  Negative predictive value (NPV) defined as the proportion of participants who have ctDNA not detected who have no evidence of recurrence.
• Association with resolution of indeterminate findings [ Time Frame: 6 years ]
  1. 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
  2. The proportion of ctDNA not detected participants whose indeterminate findings is ultimately confirmed to be benign.
• Sensitivity for local recurrence [ Time Frame: 6 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.
• Index Cancer-Specific Survival (ICSS) [ Time Frame: 6 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.
• Overall Survival (OS) [ Time Frame: 6 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.
• Rate of ctDNA clearance with adjuvant chemotherapy [ Time Frame: 6 years ]
  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.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation
• Official Title: ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation
• 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 Provided
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• 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.

Condition

• 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
• Squamous Cell Carcinoma of the Head and Neck
• Epithelial Ovarian Carcinoma
• Fallopian Tube Carcinoma
• Endometrial Carcinoma
• Renal Cell Carcinoma

Intervention

Diagnostic Test: Guardant Reveal

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

Study Groups/Cohorts

• Cohort 1: Muscle invasive carcinoma of the bladder, ureter, or renal pelvis (stage II-III)
  Intervention: Diagnostic Test: Guardant Reveal
• Cohort 2: Non-small cell lung cancer (stage II-III)
  Intervention: Diagnostic Test: Guardant Reveal
• 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
  Intervention: Diagnostic Test: Guardant Reveal
• Cohort 4: Stage IIb-III cutaneous melanoma or limited (resectable) stage IV melanoma
  Intervention: Diagnostic Test: Guardant Reveal
• Cohort 5: Esophageal or gastroesophageal junction carcinoma (stage II-III)
  Intervention: Diagnostic Test: Guardant Reveal
• Cohort 6: Gastric adenocarcinoma (stage II-III)
  Intervention: Diagnostic Test: Guardant Reveal
• Cohort 7: Surgically resected pancreatic adenocarcinoma
  Intervention: Diagnostic Test: Guardant Reveal
• 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.
  Intervention: Diagnostic Test: Guardant Reveal
• 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).
  Intervention: Diagnostic Test: Guardant Reveal
• 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).
  Intervention: Diagnostic Test: Guardant Reveal
• 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.
  Intervention: Diagnostic Test: Guardant Reveal

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 17, 2021): 1000
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 2028
• Estimated Primary Completion Date: February 2028 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Clinical Trial Operations; 8556988887; mrdoraclestudy@guardanthealth.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05059444
• Other Study ID Numbers: 02-MX-003
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Guardant Health, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Guardant Health, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Study Director; Guardant Health, Inc.

• PRS Account: Guardant Health, Inc.
• Verification Date: September 2022