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

NCT03576937 | Completed

• 1 other identifier: 18-5353
• Study Type: observational
• Target: 207
• Locations: 1 country
• Sites: 6

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.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Proportion of patients receiving targeted therapy

  Up to 18 Months

• Time to Treatment Initiation

  Up to 18 Months

• Incremental number of actionable genomic alterations

  Up to 18 Months

• Turnaround time of cfDNA vs. tissue results

  Up to 18 Months

• Costs of cfDNA vs. tissue testing

  Up to 18 Months

Other Outcomes (4)

• Response rate to immunotherapy

  Up to 18 Months

• Response duration to immunotherapy

  Up to 18 Months

• Patient reported quality of life

  Upon entry and 3 months following initiation of systemic therapy

Study Arms (2)

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

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

Interventions

GUARDANT360 DIAGNOSTIC_TEST

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

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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)

You may qualify if:

• 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;
• Standard-of-care tissue genotyping ordered or planned. Patients with tissue deemed insufficient for genotyping are eligible.
• 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.

You may not qualify if:

• Pregnancy;
• ≥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.

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (6)

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Location

BC Cancer Agency

Vancouver, British Columbia, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, Canada

Location

Ottawa Hospital Regional Cancer Centre

Ottawa, Ontario, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Location

Jewish General Hospital

Montreal, Quebec, Canada

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2018
• First Posted: July 5, 2018
• Study Start: February 12, 2019
• Primary Completion: October 30, 2020
• Study Completion: April 30, 2023
• Last Updated: May 15, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (6)