Clinical trial NCT02294578: Salivary Biomarkers for Non-small Cell Lung Cancer Detection
Official title: Prospective Blinded Evaluation of Salivary Transcriptome Biomarkers for Non-small Cell Lung Cancer Detection
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Lung Cancer
Keywords: Biomarkers
saliva
mRNA
Lead sponsor: PeriRx
Sponsor class: INDUSTRY
First posted: 2014-11-19
Enrollment: 166
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients presenting for evaluation of lung lesions suspicious for the presence of lung cancer.

Brief summary: 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.

Detailed description: 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..

Eligibility criteria: Inclusion Criteria:

* Any patient presenting to the participating institutions of affiliated clinics for evaluation or biopsy of a lung lesion suspicious for cancer.
* Patients ≥ 18 years of age
* Patients willing and able to give informed consent

Exclusion Criteria:

* Diagnosis of cancer within the last two years, excluding non-melanoma skin cancer (if \> 2 years since diagnosis, must be free of known disease \& not on current treatment for cancer).
* Prior immunosuppressive therapy or autoimmune disorder
* Known HIV infection
* Known Hepatitis infection

Primary outcomes:
measure: Performance of a pre-specified multi-marker panel (incorporating 3 of the 7 pre-specified cancer genes and the housekeeping gene)
timeFrame: Patients will be followed until their work up determines if they have benign pathology or lung cancer and the stage is determined. The complete analysis of biomarkers will occur at approximately 15 months after the start of enrollment.
Secondary outcomes:
measure: Validation of the individual mRNA biomarkers (BRAF, CCN1, EGRF, FGF19, FRS2,GREB1 and LZTS1)
timeFrame: Patients will be followed until their work up determines if they have benign pathology or lung cancer and the stage is determined. The complete analysis of biomarkers will occur at approximately 15 months after the start of enrollment.
measure: Performance of new multi-marker models
timeFrame: Patients will be followed until their work up determines if they have benign pathology or lung cancer and the stage is determined. The complete analysis of biomarkers will occur at approximately 15 months after the start of enrollment.
measure: Performance of new candidate housekeeping genes
timeFrame: Patients will be followed until their work up determines if they have benign pathology or lung cancer and the stage is determined. The complete analysis of biomarkers will occur at approximately 15 months after the start of enrollment.
Other outcomes:
Locations:
city: Warren
country: United States
facility: St. John Macomb-Oakland Hospital
state: Michigan
city: Wynnewood
country: United States
facility: Main Line Health Ststem
state: Pennsylvania
Study officials:
affiliation: PeriRx, LLC
name: Jack L Martin, MD
role: STUDY_CHAIR
References: