Gene Expression Levels in Predicting Treatment Response in Patients With Stage IV Non-small Cell Lung Cancer
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|ClinicalTrials.gov Identifier: NCT02145078|
Recruitment Status : Terminated (Slow accrual.)
First Posted : May 22, 2014
Results First Posted : September 24, 2020
Last Update Posted : September 24, 2020
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Non-small Cell Lung Cancer Stage IV Non-small Cell Lung Cancer||Drug: docetaxel Drug: pemetrexed disodium Drug: gemcitabine hydrochloride Other: laboratory biomarker analysis||Not Applicable|
I. To describe the association between baseline gene expression levels at the protein and messenger ribonucleic acid (mRNA) level and best treatment response after two cycles of single-agent or multi-agent chemotherapy
I. To describe changes in protein and mRNA levels of ribonucleotide reductase M1 (RRM1), thymidylate synthetase (TS), and excision repair cross-complementing rodent repair deficiency, complementation group 1 (ERCC1) in serial biopsies obtained from patients being treated with gemcitabine (gemcitabine hydrochloride), pemetrexed (pemetrexed disodium), and platinum.
II. To describe the association between changes in marker levels and changes in tumor diameters.
I. To explore the relationship between marker levels in circulating tumor cells and solid tumor specimens.
II. To explore the relationship between marker levels in viable peripheral blood mononuclear cells (PBMCs), circulating tumor cells, and tumor specimens.
III. Should sufficient amounts and numbers of tumor specimens remain after these analyses, they will be used to assess if other genes implicated in non-small cell lung cancer (NSCLC) outcome and response to treatment might be useful as prognostic or predictive markers for patient outcome.
Patients receive 1 of 3 chemotherapy regimens at the discretion of the primary oncologist, including docetaxel intravenously (IV) on day 1, pemetrexed disodium IV on day 1, or gemcitabine hydrochloride IV on days 1 and 8. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. After course 2, patients may continue treatment off-study at the discretion of the treating physician.
After completion of study treatment, patients are followed up for 12 months.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||4 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Trial of Platinum, Gemcitabine, or Pemetrexed Single- or Multi-Agent Therapy With Serial Tumor Specimen Collection in Patients With Advanced Non-Small-Cell Lung Cancer|
|Study Start Date :||June 2014|
|Actual Primary Completion Date :||June 18, 2015|
|Actual Study Completion Date :||March 7, 2017|
Experimental: Treatment (chemotherapy regimen)
Patients receive 1 of 4 chemotherapy regimens at the discretion of the primary oncologist following institutional guidelines, including cisplatin, carboplatin, pemetrexed disodium IV on day 1, or gemcitabine hydrochloride IV on days 1 and 8. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. After course 2, patients may continue treatment off-study at the discretion of the treating physician.
Drug: pemetrexed disodium
Drug: gemcitabine hydrochloride
Other: laboratory biomarker analysis
- Baseline Marker Measurement [ Time Frame: Baseline ]A univariable regression of continuous disease response on baseline marker value will be performed. A multivariable regression model adjusted for clinical covariates will be evaluated as well. Expression levels of RRM1, TS, BRCA1, and other molecules and disease response after course 2 will be log-transformed.
- Change in Biomarker Expression Levels [ Time Frame: Baseline to up to 8 weeks (after course 2) ]Evaluated using Pearson correlation. If data are not normally distributed after log transformation, a non-parametric method (e.g., Spearman correlation) will be used.
- Overall Survival (OS) [ Time Frame: From the date of protocol-specified treatment initiation to the date of death or last observation, assessed up to 12 months ]Since, the study was canceled due to slow accrual, no biomarkers were measured; therefore, no analysis with biomarkers. Only the OS will be calculated.
- Progression-free Survival (PFS) [ Time Frame: From the date of protocol-specified treatment initiation to the date of progression, death, or last observation, assessed up to 12 months ]Each biomarker evaluated using its expression level (continuous variable) and dichotomous form (based on a median cutoff). A univariable Cox regression model will be used to assess the relationship of expression levels of each biomarker to PFS. In addition, for the dichotomous variables, the sample will be divided into those above and below the median for each biomarker. PFS probabilities for each group will be estimated using the Kaplan-Meier method, with standard errors based on Greenwood's formula. Log rank tests will be used to determine the level of significance between survival curves. Since, the study was canceled due to slow accrual, no biomarkers were measured; therefore, no analysis with biomarkers. Only the PFS will be calculated.
- Expression Levels of Biomarkers and Other Molecules [ Time Frame: Up to 8 weeks (end of course 2) ]To assess the relationship between expression levels of RRM1, TS, BRCA1, and other molecules and demographic and disease variables, the Wilcoxon rank sum test or Kruskal-Wallis test for dichotomous or polychotomous categorical variables (such as sex, and histology) and the Spearman correlation coefficient for continuous ordinal variables (such as age or stage) will be used.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02145078
|United States, Michigan|
|Barbara Ann Karmanos Cancer Institute|
|Detroit, Michigan, United States, 48201|
|Principal Investigator:||Gerold Bepler||Barbara Ann Karmanos Cancer Institute|