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

Non-small Cell Lung Cancer Clinical Trial

— VALUE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03576937
• Other study ID #: 18-5353
• Status: Completed
• Start date: February 12, 2019
• Est. completion date: April 30, 2023

Study information

• Verified date: May 2023
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 207
• Est. completion date: April 30, 2023
• Est. primary completion date: October 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Non-small Cell Lung Cancer

Intervention

Diagnostic Test:
• GUARDANT360
GUARDANT360 is a validated cfDNA next-generation sequencing assay that identifies variants in 73 genes associated with several cancers.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Response rate to immunotherapy	Assess response rate in patients (Cohort 1) who received single agent or combination immunotherapy.	Up to 18 Months
Other	Response duration to immunotherapy	Assess response duration in patients (Cohort 1) who received single agent or combination immunotherapy.	Up to 18 Months
Other	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
Other	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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