Achieving Value in Cancer Diagnostics: Blood Versus Tissue Molecular Profiling - a Prospective Canadian Study
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Non-small Cell Lung Cancer
- Sponsor
- University Health Network, Toronto
- Enrollment
- 207
- Locations
- 6
- Primary Endpoint
- Response rate to first-line therapy
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients with non-small cell lung cancer (NSCLC) with:
- •Histologically-proven, advanced (Stage IIIB or IV not eligible for curative intent treatment, or relapsed/recurrent) disease;
- •Non-squamous histology (mixed adenocarcinoma histology is allowed);
- •Never smoking or light smoking history (≤10 pack years);
- •Measureable disease by RECIST 1.1;
- •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;
- •Age ≥ 18 years;
- •Ability to provide written informed consent;
- •Agreement to provide blood sample prior to starting systemic treatment;
- •Eligibility for targeted therapy in the opinion of the investigator;
Exclusion Criteria
- •≥10 pack year smoking history;
- •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 resection of metastatic disease if the resected metastasis was the only site of measurable disease;
- •Radiation of a metastatic lesion or residual disease if administered to the only site(s) of advanced disease;
- •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.
Outcomes
Primary Outcomes
Response rate to first-line therapy
Time Frame: Up to 18 Months
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.
Secondary Outcomes
- Costs of cfDNA vs. tissue testing(Up to 18 Months)
- Proportion of patients receiving targeted therapy(Up to 18 Months)
- Time to Treatment Initiation(Up to 18 Months)
- Turnaround time of cfDNA vs. tissue results(Up to 18 Months)
- Incremental number of actionable genomic alterations(Up to 18 Months)