ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation

Study Overview
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Brief Summary
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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.

Official Title
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ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation

Conditions
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Endometrial Carcinoma, 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, Renal Cell Carcinoma

Intervention / Treatment
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* Diagnostic Test: Guardant Reveal


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort 1: Muscle invasive carcinoma of the bladder, ureter, or renal pelvis (stage II-III)<br> | Diagnostic Test: Guardant Reveal<br>* Guardant Reveal is a minimal residual disease (MRD) panel for use in recurrence detection of early-stage solid tumors.<br>|
| Cohort 2: Non-small cell lung cancer (stage II-III)<br> | Diagnostic Test: Guardant Reveal<br>* Guardant Reveal is a minimal residual disease (MRD) panel for use in recurrence detection of early-stage solid tumors.<br>|
| Cohort 3: Invasive breast carcinoma with all of the following:<br>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<br>* Guardant Reveal is a minimal residual disease (MRD) panel for use in recurrence detection of early-stage solid tumors.<br>|
| Cohort 4: Stage IIb-III cutaneous melanoma or limited (resectable) stage IV melanoma<br> | Diagnostic Test: Guardant Reveal<br>* Guardant Reveal is a minimal residual disease (MRD) panel for use in recurrence detection of early-stage solid tumors.<br>|
| Cohort 5: Esophageal or gastroesophageal junction carcinoma (stage II-III)<br> | Diagnostic Test: Guardant Reveal<br>* Guardant Reveal is a minimal residual disease (MRD) panel for use in recurrence detection of early-stage solid tumors.<br>|
| Cohort 6: Gastric adenocarcinoma (stage II-III)<br> | Diagnostic Test: Guardant Reveal<br>* Guardant Reveal is a minimal residual disease (MRD) panel for use in recurrence detection of early-stage solid tumors.<br>|
| Cohort 7: Surgically resected pancreatic adenocarcinoma<br> | Diagnostic Test: Guardant Reveal<br>* Guardant Reveal is a minimal residual disease (MRD) panel for use in recurrence detection of early-stage solid tumors.<br>|
| Cohort 8: Invasive squamous cell carcinoma of the head and neck<br>Includes stage I-III oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, nasal cavity, paranasal sinus, and salivary gland cancers. | Diagnostic Test: Guardant Reveal<br>* Guardant Reveal is a minimal residual disease (MRD) panel for use in recurrence detection of early-stage solid tumors.<br>|
| Cohort 9: High-risk epithelial ovarian or Fallopian tube carcinoma<br>Defined as stage IC-III or stage I that has high grade (grade 3-4) or clear cell histology). | Diagnostic Test: Guardant Reveal<br>* Guardant Reveal is a minimal residual disease (MRD) panel for use in recurrence detection of early-stage solid tumors.<br>|
| Cohort 10: High-risk endometrial carcinoma<br>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<br>* Guardant Reveal is a minimal residual disease (MRD) panel for use in recurrence detection of early-stage solid tumors.<br>|
| Cohort 11: High-risk renal cell carcinoma<br>Defined as high grade (grade 3-4) stage II, stage III or limited (resectable) stage IV treated with curative intent. | Diagnostic Test: Guardant Reveal<br>* Guardant Reveal is a minimal residual disease (MRD) panel for use in recurrence detection of early-stage solid tumors.<br>|

What is the study measuring?
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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 |