Clinical trial NCT03576937: Achieving Value in Cancer Diagnostics: Blood Versus Tissue Molecular Profiling - a Prospective Canadian Study
Official title: Achieving Value in Cancer Diagnostics: Blood Versus Tissue Molecular Profiling - a Prospective Canadian Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Non-small Cell Lung Cancer
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2018-07-05
Enrollment: 207
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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)

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Response rate to first-line therapy
timeFrame: Up to 18 Months
Secondary outcomes:
measure: Proportion of patients receiving targeted therapy
timeFrame: Up to 18 Months
measure: Time to Treatment Initiation
timeFrame: Up to 18 Months
measure: Incremental number of actionable genomic alterations
timeFrame: Up to 18 Months
measure: Turnaround time of cfDNA vs. tissue results
timeFrame: Up to 18 Months
measure: Costs of cfDNA vs. tissue testing
timeFrame: Up to 18 Months
Other outcomes:
measure: Response rate to immunotherapy
timeFrame: Up to 18 Months
measure: Response duration to immunotherapy
timeFrame: Up to 18 Months
measure: Patient reported quality of life
timeFrame: Upon entry and 3 months following initiation of systemic therapy
measure: Patient willingness-to-pay
timeFrame: Within 30 days of study enrollment
Locations:
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Vancouver
country: Canada
facility: BC Cancer Agency
state: British Columbia
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
Study officials:
References: