Noninvasive vs. Invasive Lung Evaluation (NILE)

Tumor derived cell free DNA (cfDNA) is increasingly used in the clinic to obtain genotype information about lung cancer, but its concordance with concurrent tumor-derived sequenced data is not known. The purpose of the trial is to determine the non-inferiority of cfDNA-based vs. tumor tissue-based genotyping as it pertains to the detection of National Comprehensive Cancer Network (NCCN)-recommended biomarkers in first line, treatment naive, non-squamous Non-Small Cell Lung Cancer (NSCLC).

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Diagnostic test: Guardant360

• Study Type: Observational
• Enrollment (Actual): 306

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Treatment-naïve metastatic non-squamous non-small cell lung cancer (NSCLC).

Description

Inclusion Criteria:

• Patients with NSCLC, which is: (1) Biopsy-proven (confirmatory biopsy must have been collected within 12 months prior to enrollment), (2) Metastatic (Stage IV, Stage IIIB when curative intent is not an option, or relapsed/recurrent disease after original diagnosis of Stage I-IIIA), (3) Non-squamous histology (mixed squamous and adenocarcinoma is allowed), (4) No prior treatment for advanced stage NSCLC: (a) Resection of or radiation to a single metastatic site is allowed if there are other untreated and measurable sites of metastatic disease at the time of enrollment. (b) Patients who have previously undergone surgical resection or radiation for Stage I-IIIA NSCLC are eligible if primary treatment was completed at least 6 months prior to the development of metastatic disease; for patients who received adjuvant systemic therapy, the last dose of treatment must be given at least 6 weeks prior to enrollment.
• Age ≥ 18 years
• Ability to understand a written informed consent document, and the willingness to sign it.
• Willingness to provide blood sample at the time points of pre-treatment, approximately 2 weeks after initiation of systemic treatment, and end of study).
• Patient has or will have standard-of-care tissue genotyping ordered. If the physician intends to order tissue genotyping, but there is insufficient material for analysis, the patient is still eligible for enrollment.

Exclusion Criteria:

• Pregnancy
• Any other concurrent malignancy except for localized, non-melanoma, cutaneous cancer or non-invasive cervical cancer. Any prior cancer other than NSCLC must have occurred more than 2 years prior to study entry with no evidence of currently active disease.
• Prior treatment for metastatic NSCLC including but not limited to: (1) Systemic treatment (targeted therapy, chemotherapy, immunotherapy, biologic therapy, etc.), (2) Resection of a metastatic lesion if the resected metastasis had been the only site of measurable metastatic disease, or resection of more than one metastatic lesion, (3) Radiation of a metastatic lesion or resection bed if given to the only measurable site of metastatic disease, or radiation to more than one metastatic lesion.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Treatment-naive metastatic non-squamous NSCLC	Diagnostic test: Guardant360; Guardant360 is a comprehensive, non-invasive tumor sequencing test.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Demonstrate the non-inferiority of cfDNA-based vs. tumor tissue-based genotyping	The proportion of subjects for whom a genetic alteration is found in at least one of seven genes (EGFR, ALK, ROS1, BRAF, MET, ERBB2, RET) by testing tumor tissue will be compared to the proportion of subjects for whom a genetic alteration is found in at least one of the same genes by testing cfDNA.	34 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	The proportion of subjects with complete or partial tumor response as determined by the investigator. This will be assessed for the overall population and for the subpopulation of subjects who are identified by either tissue or cfDNA as having actionable EGFR activating mutations, ALK fusions, ROS1 fusions, and BRAF V600E mutations and who are subsequently treated with tyrosine kinase inhibitors.	34 months
Turnaround Time for cfDNA vs. Tissue Results	The time (in days) from the date of request for genetic testing to the report date for cfDNA and for tumor tissue.	34 months
Time to Treatment Initiation	The number of days from the date of study enrollment until the date that systemic or localized treatment is initiated.	34 months
Quantity Not Sufficient Rate of Tissue for Complete NCCN Biomarker Testing	The proportion of subjects deemed to have quantity not sufficient for tumor tissue testing of any of seven genes (EGFR, ALK, ROS1, BRAF, MET, ERBB2, RET) due to any of the following reasons: 1) insufficient tumor specimen for the genotyping tests to be performed, or 2) tumor cellularity below lab-dictated minimal requirements, or 3) no results available within 45 days of enrollment.	34 months
Tissue Incomplete Rate of Tissue for NCCN Biomarker Testing	The proportion of subjects with tumor tissue testing results not available for all seven genes (EGFR, ALK, ROS1, BRAF, MET, ERBB2, RET) and with no alterations detected among the genes that were tested.	34 months
Tumor Not Detected Rate of cfDNA in Blood	The proportion of subjects for whom cfDNA could not be detected in blood.	34 months
Sensitivity, Specificity, and Diagnostic Accuracy of Non-NCCN Biomarkers on the Guardant360 Panel	This objective applies to genes included in the Guardant360 panel other than EGFR, ALK, ROS1, BRAF, MET, ERBB2, RET and to subjects for whom both cfDNA and tumor tissue testing results are available. Diagnostic accuracy will include calculations for sensitivity, specificity, positive predictive value, and negative predictive value comparing tissue to cfDNA results and vice versa.	34 months
Rate of Discovery of Genomically Mediated, Acquired Resistance to Targeted Therapies in the Biomarker-Positive Subsets	Among subjects with tumor genetic alterations in EGFR, ALK, ROS1, BRAF, MET, ERBB2, or RET, the proportion with new (compared to baseline) genetic alterations in cfDNA at the time of disease progression following treatment with a therapy targeting the specific genetic alteration.	34 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liquid Biopsy Rescue Rate of QNS Tissue Samples	Among subjects with tumor tissue quantity not sufficient for genetic testing, the proportion that had cfDNA detected.	34 months

Collaborators and Investigators

• Sponsor: Guardant Health, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2016
• Primary Completion (Actual): November 23, 2020
• Study Completion (Actual): November 23, 2020

Study Registration Dates

• First Submitted: July 13, 2018
• First Submitted That Met QC Criteria: August 2, 2018
• First Posted (Actual): August 3, 2018

Study Record Updates

• Last Update Posted (Actual): May 3, 2021
• Last Update Submitted That Met QC Criteria: April 29, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: GH03-001

Drug and device information, study documents

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