This phase II trial studies how well MLN4924 (pevonedistat), carboplatin, and paclitaxel work in treating patients with stage IIIB or IV non-small cell lung cancer. Pevonedistat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pevonedistat together with carboplatin and paclitaxel may work better in treating patients with non-small cell lung cancer when compared with other standard chemotherapy drugs.
Name: Carboplatin
Name: Paclitaxel
Name: Pevonedistat
Description: Defined as the proportion of evaluable subjects with a response. Response will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria. Patients will be re-evaluated for response every 6 weeks. The number and frequencies of responses will be summarized in tabular format. The ORR will be calculated and reported along with the corresponding 95% confidence interval which will be constructed using the Wilson score method.
Measure: Overall response rate (ORR) Time: Up to 5 yearsDescription: Will be analyzed using the Kaplan-Meier method. Median PFS will be calculated along with the corresponding 95% confidence interval which will be constructed using the non-parametric Brookmeyer-Crowley method.
Measure: Progression free survival (PFS) Time: From the start of treatment to time of progression or death, whichever occurs first, assessed for up to 5 yearsDescription: Defined as the duration of time from start of treatment to time of death. Analyzed using the Kaplan-Meier method. Median OS will be calculated along with the corresponding 95% confidence interval which will be constructed using the non-parametric Brookmeyer-Crowley method.
Measure: Overall survival (OS) Time: From the start of treatment to time of death; assessed for up to 5 yearsDescription: Evaluated by type and severity using the revised National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. All toxicities observed will be summarized in terms of types and severity. Toxicities will be tabulated and summarized by organ systems. Incidence rates of toxicities will be analyzed descriptively.
Measure: Incidence of adverse events Time: Up to 5 yearsDescription: Summarized using descriptive statistics. Ratios of the day 1 pre-treatment over the 6 hours post-infusion levels will be calculated and reported along with the corresponding 95% confidence intervals. A one sample t-test or Wilcoxon Signed Rank test will be used to evaluate changes from the day 1 pre-treatment to the 6 hours post-infusion assessment. A two-sample t-test or nonparametric Wilcoxon Rank Sum test will be used to compared changes in NQO1 expression levels from day 1 pre-treatment to 6 hours post-infusion between responders and non-responders.
Measure: NQO1 expression levels Time: Day 1 pre-treatment and 6 hours post-infusionDescription: Summarized using descriptive statistics. Ratios of the day 1 pre-treatment over the 6 hours post-infusion levels will be calculated and reported along with the corresponding 95% confidence intervals. A one sample t-test or Wilcoxon Signed Rank test will be used to evaluate changes from the day 1 pre-treatment to the 6 hours post-infusion assessment. A two-sample t-test or nonparametric Wilcoxon Rank Sum test will be used to compared changes in SLC7A11 expression levels from day 1 pre-treatment to 6 hours post-infusion between responders and non-responders.
Measure: SLC7A11 expression levels Time: Day 1 pre-treatment and 6 hours post-infusionDescription: Qualitative assessment of tumor NAE1 expression will be conducted by evaluating descriptive summaries of NAE1 expression levels. Changes from the pre-treatment to post-infusion assessment will be evaluated using a paired t-test or nonparametric Wilcoxon Signed Rank test.
Measure: NAE1 expression levels Time: Pre-treatment and 6 hours post-infusion on cycle 1, day 1Description: Qualitative assessment of tumor UBC12 expression will be conducted by evaluating descriptive summaries of UBC12 expression levels. Changes from the pre-treatment to post-infusion assessment will be evaluated using a paired t-test or nonparametric Wilcoxon Signed Rank test.
Measure: UBC12 expression level Time: Pre-treatment and 6 hours post-infusion on cycle 1, day 1Description: A linear mixed effects model with patient -specific random effects will be utilized to compared changes in gammaH2AX. Changes from the pre-treatment to post-infusion assessment will be evaluated using a paired t-test or nonparametric Wilcoxon Signed Rank test.
Measure: GammaH2AX in circulating tumor cells (CTCs) Time: Baseline and after treatment with pevonedistatDescription: A linear mixed effects model with patient -specific random effects will be utilized to compared changes in RAD51. Changes from the pre-treatment to post-infusion assessment will be evaluated using a paired t-test or nonparametric Wilcoxon Signed Rank test.
Measure: RAD51 in CTCs Time: Baseline and after treatment with pevonedistatDescription: Summarized in terms of means, standard deviations, and ranges, stratified by assessment time point. Changes from the pre-treatment to post-infusion assessment will be evaluated using a paired t-test or nonparametric Wilcoxon Signed Rank test.
Measure: ATF3 expression levels Time: Pre-treatment and 6 hours post-infusion on cycle 1, day 1Description: Summarized in terms of means, standard deviations, and ranges, stratified by assessment time point. Changes from the pre-treatment to post-infusion assessment will be evaluated using a paired t-test or nonparametric Wilcoxon Signed Rank test.
Measure: B2M expression levels Time: Pre-treatment and 6 hours post-infusion on cycle 1, day 1Description: Summarized in terms of means, standard deviations, and ranges, stratified by assessment time point. Changes from the pre-treatment to post-infusion assessment will be evaluated using a paired t-test or nonparametric Wilcoxon Signed Rank test.
Measure: GCLM expression levels Time: Pre-treatment and 6 hours post-infusion on cycle 1, day 1Description: Summarized in terms of means, standard deviations, and ranges, stratified by assessment time point. Changes from the pre-treatment to post-infusion assessment will be evaluated using a paired t-test or nonparametric Wilcoxon Signed Rank test.
Measure: GSR expression levels Time: Pre-treatment and 6 hours post-infusion on cycle 1, day 1Description: Summarized in terms of means, standard deviations, and ranges, stratified by assessment time point. Changes from the pre-treatment to post-infusion assessment will be evaluated using a paired t-test or nonparametric Wilcoxon Signed Rank test.
Measure: MAG1 expression levels Time: Pre-treatment and 6 hours post-infusion on cycle 1, day 1Description: Summarized in terms of means, standard deviations, and ranges, stratified by assessment time point. Changes from the pre-treatment to post-infusion assessment will be evaluated using a paired t-test or nonparametric Wilcoxon Signed Rank test.
Measure: RPLP0 expression levels Time: Pre-treatment and 6 hours post-infusion on cycle 1, day 1Description: Summarized in terms of means, standard deviations, and ranges, stratified by assessment time point. Changes from the pre-treatment to post-infusion assessment will be evaluated using a paired t-test or nonparametric Wilcoxon Signed Rank test.
Measure: SRXN1 expression levels Time: Pre-treatment and 6 hours post-infusion on cycle 1, day 1Description: Summarized in terms of means, standard deviations, and ranges, stratified by assessment time point. Changes from the pre-treatment to post-infusion assessment will be evaluated using a paired t-test or nonparametric Wilcoxon Signed Rank test.
Measure: TXNRD1 expression levels Time: Pre-treatment and 6 hours post-infusion on cycle 1, day 1Description: Summarized in terms of means, standard deviations, and ranges, stratified by assessment time point. Changes from the pre-treatment to post-infusion assessment will be evaluated using a paired t-test or nonparametric Wilcoxon Signed Rank test.
Measure: UBC expression levels Time: Pre-treatment and 6 hours post-infusion on cycle 1, day 1Description: Summarized in terms of means, standard deviations, medians, and ranges, stratified by assessment time point. Changes in PK parameters between assessment time points will be evaluated using a paired t-test.
Measure: Pharmacokinetics (PK) parameters Time: Pre-treatment and 6 hours post-infusion on cycle 1, day 1Allocation: N/A
Single Group Assignment
There is one SNP
sensitizing EGFR, ALK, ROS1, NTRK, BRAF V600E mutation positive) must have received prior treatment with Food and Drug Administration (FDA) approved targeted therapy for patients for which FDA approved targeted therapies is available. --- V600E ---