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Report for Clinical Trial NCT03965689

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase 2 Study of MLN4924 (Pevonedistat) in Combination With Carboplatin and Paclitaxel in Advanced NSCLC Previously Treated With Immunotherapy

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.

NCT03965689 Metastatic Lung Non-Small Cell Squamous Carcinoma Metastatic Lung Non-Squamous Non-Small Cell Carcinoma Stage IIIB Lung Cancer AJCC v8 Stage IV Lung Cancer AJCC v8 Stage IVA Lung Cancer AJCC v8 Stage IVB Lung Cancer AJCC v8 Unresectable Lung Non-Small Cell Carcinoma Unresectable Lung Non-Squamous No Unresectable Lung Non-Squamous Non-Small Cell Carcinoma
MeSH:Carcinoma Lung Neoplasms Carcinoma, Non-Small-Cell Lung Carcinoma, Squamous Cell
HPO:Carcinoma Neoplasm of the lung Non-small cell lung carcinoma Squamous cell carcinoma

3 Interventions

Name: Carboplatin

Description: Given IV
Type: Drug
Group Labels: 1

Treatment (paclitaxel, carboplatin, pevonedistat)

Name: Paclitaxel

Description: Given IV
Type: Drug
Group Labels: 1

Treatment (paclitaxel, carboplatin, pevonedistat)

Name: Pevonedistat

Description: Given IV
Type: Drug
Group Labels: 1

Treatment (paclitaxel, carboplatin, pevonedistat)


Primary Outcomes

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 years

Secondary Outcomes

Description: 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 years

Description: 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 years

Description: 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 years

Other Outcomes

Description: 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-infusion

Description: 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-infusion

Description: 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 1

Description: 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 1

Description: 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 pevonedistat

Description: 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 pevonedistat

Description: 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 1

Description: 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 1

Description: 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 1

Description: 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 1

Description: 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 1

Description: 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 1

Description: 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 1

Description: 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 1

Description: 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 1

Description: 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 1

Purpose: Treatment

Allocation: N/A

Single Group Assignment


There is one SNP

SNPs


1 V600E

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 ---



HPO Nodes


HPO: