Achieving Value in Cancer Diagnostics: Blood Versus Tissue Molecular Profiling - a Prospective Canadian Study (VALUE)

Current guidelines in non-small cell lung cancer recommend genomic assessment for mutations in EGFR and BRAF, gene rearrangements in ALK and ROS1, and resistance mutations such as T790M upon progression during EGFR inhibitor therapy. However, obtaining sufficient tumour tissue to test for these molecular alterations, as well as those with emerging targeted therapies, is challenging in lung cancer. A promising method to improve molecular diagnostic testing in lung and other cancers is the use of circulating cell-free DNA (cfDNA) obtained from blood samples or liquid biopsies. This multi-centre prospective study will compare blood-based profiling (using the GUARDANT360 assay) to standard of care tissue-based profiling within the Canadian system.

Study Overview

• Status: Completed
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Diagnostic test: GUARDANT360

• Study Type: Observational
• Enrollment (Actual): 207

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Tom Baker Cancer Centre
  • British Columbia
    • Vancouver, British Columbia, Canada
      • BC Cancer Agency
  • Ontario
    • Hamilton, Ontario, Canada
      • Juravinski Cancer Centre
    • Ottawa, Ontario, Canada
      • Ottawa Hospital Regional Cancer Centre
    • Toronto, Ontario, Canada
      • Princess Margaret Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada
      • Jewish General Hospital

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Non-small cell lung cancer patients (Stage IIIB or IV not eligible for curative intent treatment, or relapsed/recurrent disease)

Description

Inclusion Criteria:

Patients with non-small cell lung cancer (NSCLC) with:

1. Histologically-proven, advanced (Stage IIIB or IV not eligible for curative intent treatment, or relapsed/recurrent) disease;
2. Non-squamous histology (mixed adenocarcinoma histology is allowed);
3. Never smoking or light smoking history (≤10 pack years);
4. Measureable disease by RECIST 1.1;
5. Patients who have previously received curative therapy are eligible if primary treatment was completed at least 6 months prior to the development of advanced disease; for patients who received adjuvant systemic therapy, the last dose of treatment must have been given at least 6 weeks prior to enrollment;
6. Age ≥ 18 years;
7. Ability to provide written informed consent;
8. Agreement to provide blood sample prior to starting systemic treatment;
9. Eligibility for targeted therapy in the opinion of the investigator;
10. Standard-of-care tissue genotyping ordered or planned. Patients with tissue deemed insufficient for genotyping are eligible.
11. Cohort 2 only: evidence of disease progression on prior targeted tyrosine kinase inhibitor or other targeted therapy for EGFR including T790M, ALK, ROS-1 or BRAF-deranged advanced NSCLC. Patients progressing on 1st or 2nd generation EGFR TKI must have undergone SOC testing for EGFR T790M. If blood- or tissue-negative for T790M, the patient is eligible for this study. If T790M-positive, the patient must have progressed on a T790M inhibitor to be eligible. Intervening systemic therapy such as chemotherapy or immunotherapy is permitted.

Exclusion Criteria:

1. Pregnancy;
2. ≥10 pack year smoking history;
3. 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;
4. Prior resection of metastatic disease if the resected metastasis was the only site of measurable disease;
5. Radiation of a metastatic lesion or residual disease if administered to the only site(s) of advanced disease;
6. Cohort 1 only: Prior systemic treatment for metastatic NSCLC including but not limited to targeted therapy, chemotherapy, immunotherapy, or biologic therapy. Adjuvant therapy is permitted at least 6 weeks prior to enrollment.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort 1; Patients with advanced (incurable stage IIIB or IV), histologically proven, non-squamous NSCLC who are never- or light-smokers (≤10 pack year smoking history) and are being considered for systemic therapy in the first line setting are eligible. Blood will be collected prior to first line treatment for testing cfDNA with the GUARDANT360 assay. Testing of available diagnostic tissue for genomic abnormalities will be performed in all patients per standard of care at the participating sites.	Diagnostic test: GUARDANT360; GUARDANT360 is a validated cfDNA next-generation sequencing assay that identifies variants in 73 genes associated with several cancers.
Cohort 2; Patients with advanced non-squamous NSCLC with known oncogenic drivers (such as EGFR, ALK, ROS-1, BRAF) that have failed tyrosine kinase inhibitor (TKI) therapy, and are being considered for subsequent therapy. Blood will be collected from patients at time of progression on TKI therapy for cfDNA testing with the GUARDANT360 assay. Testing of available diagnostic tissue for genomic abnormalities will be performed in all patients per standard of care at the participating sites.	Diagnostic test: GUARDANT360; GUARDANT360 is a validated cfDNA next-generation sequencing assay that identifies variants in 73 genes associated with several cancers.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate to first-line therapy	Measure best response to first-line therapy using investigator-assessed RECIST 1.1, including progression free survival and time to treatment failure, in patients with advanced lung adenocarcinoma using the cfDNA GUARDANT360 assay versus standard of care tissue genotyping.	Up to 18 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients receiving targeted therapy	Compare the proportion of patients receiving targeted therapy using the cfDNA GUARDANT360 assay versus standard of care tissue genotyping.	Up to 18 Months
Time to Treatment Initiation	The time to treatment initiation using both genotyping methods, will be calculated as the number of days from the date of pathologic or clinical stage IV NSCLC diagnosis until initiation of systemic treatment. This will be compared to the turnaround time for GUARDANT360 results.	Up to 18 Months
Incremental number of actionable genomic alterations	Count the number of actionable genomic alterations identified in cfDNA that were not identified in tumour tissue standard of care testing.	Up to 18 Months
Turnaround time of cfDNA vs. tissue results	Calculate the time (in days) from the date of request for testing to the report date for both genotyping methods.	Up to 18 Months
Costs of cfDNA vs. tissue testing	Cost consequence analysis to examine incremental mean direct and indirect costs in Canadian dollars between the two approaches (cfDNA testing vs tumour tissue genotyping).	Up to 18 Months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate to immunotherapy	Assess response rate in patients (Cohort 1) who received single agent or combination immunotherapy.	Up to 18 Months
Response duration to immunotherapy	Assess response duration in patients (Cohort 1) who received single agent or combination immunotherapy.	Up to 18 Months
Patient reported quality of life	Patient quality of life will be measured using the EQ5D-5L, which will be administered upon entry to the study and 3 months after starting systemic therapy.	Upon entry and 3 months following initiation of systemic therapy
Patient willingness-to-pay	Evaluate patient willingness-to-pay for using a next generation sequencing assay, such as the GUARDANT360, using a validated patient survey.	Within 30 days of study enrollment

Collaborators and Investigators

• Sponsor: University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2019
• Primary Completion (Actual): October 30, 2020
• Study Completion (Actual): April 30, 2023

Study Registration Dates

• First Submitted: June 22, 2018
• First Submitted That Met QC Criteria: June 22, 2018
• First Posted (Actual): July 5, 2018

Study Record Updates

• Last Update Posted (Actual): May 15, 2023
• Last Update Submitted That Met QC Criteria: May 12, 2023
• Last Verified: May 1, 2023

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: 18-5353

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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