Salivary Biomarkers for Non-small Cell Lung Cancer Detection
| Status: | Recruiting |
|---|---|
| Conditions: | Lung Cancer, Lung Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/17/2018 |
| Start Date: | December 2014 |
| End Date: | March 2019 |
| Contact: | Jack L Martin, MD |
| Email: | Martinj@mlhs.org |
| Phone: | 610 544 3500 |
Prospective Blinded Evaluation of Salivary Transcriptome Biomarkers for Non-small Cell Lung Cancer Detection
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.
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.
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..
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..
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
We found this trial at
2
sites
Click here to add this to my saved trials
Click here to add this to my saved trials