The investigators plan to recruit patients for a prospective study in patients in need of
evaluation for lung lesions suspicious for cancer. Saliva samples will be collected
before diagnostic evaluation including biopsy with subsequent blinded examination of the
salivary markers without knowledge of the disease status. This prospective recruitment
with retrospective blinded evaluation or PRoBE design satisfies the highest standards
recommended by the National Cancer Institute for biomarker development. This process
limits the selection bias that can confound retrospective studies. As the primary
endpoint, a pre-specified multi-marker panel will be evaluated based on the combination
of sensitivity and specificity. In addition, seven pre-specified individual candidate
mRNA cancer markers and six internal reference or "housekeeping" genes will be evaluated.
The performance of new multi-marker panels will also be assessed and compared with the
prior pre-specified model based on sensitivity and specificity combinations as well as
the area under the receiver operating characteristic curve.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02294578.
Consecutive eligible patients presenting to the study institutions and associated clinics
will be enrolled. Inclusion and exclusion criteria are detailed separately in the section
on eligibility. The target enrollment population listed in the study design section
provides a greater than 85% power to achieve the pre-specified goal for the sensitivity
and specificity of the pre-specified model. Saliva will be collected in vials pre filled
with mRNA stabilizer. Seven mRNA biomarkers (BRAF, CCNI, EGRF, FGF19, FRS2, GREB1, and
LZTS1) will be measured in a central laboratory by quantitative PCR with the laboratory
personnel blinded to the patient diagnosis. The primary outcome is the validation of a
pre-specified multi-marker model. This pre-specified model incorporates 3 of the cancer
genes and the housekeeping gene. The model will be validated based on the sum of
sensitivity and specificity exceeding 1.3 with the lower limit of the 95% confidence
interval exceeding 1.0. A secondary endpoint is the development of new multi-maker models
with potential improved performance. These new models will be developed by logistic
regression and compared with the pre-specified model based on the area under the receiver
operating characteristic curve and the maximum sum of sensitivity and specificity.
Individual candidate biomarkers will also be validated based on a statistically
significant up-regulation in cancer patients compared with controls. Potential new
housekeeping genes will be evaluated based on their equivalence in cancer and control as
well as their performance in multi-marker models in comparison with the pre-specified
housekeeping gene which is GADPH..
Trial PhaseNo phase specified
Trial TypeNot provided by clinicaltrials.gov
