Binimetinib With Docetaxel in Treating Patients With Previously Treated, Stage IV Non-small Cell Lung Cancer
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|ClinicalTrials.gov Identifier: NCT02451865|
Recruitment Status : Withdrawn
First Posted : May 22, 2015
Last Update Posted : July 11, 2016
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Non-Small Cell Lung Carcinoma Stage IV Non-Small Cell Lung Cancer||Drug: Binimetinib Drug: Docetaxel Other: Laboratory Biomarker Analysis||Phase 1|
I. Evaluate the safety and tolerability of increasing doses of MEK162 (binimetinib) with docetaxel 75 mg/m2 every 21 days in patients with stage IV non-small cell lung cancer (NSCLC) that have progressed after at least one prior systemic therapy.
I. Determine objective tumor response rate (RR) as defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 with MEK162 and standard doses of docetaxel in stage IV NSCLC.
II. Determine progression free survival (PFS) of MEK162 and standard doses of docetaxel.
III. Evaluate the pharmacokinetic profile of MEK162 when given along with docetaxel.
I. Evaluate tissue biomarkers in baseline tumors and at the time of progression to correlate with clinical outcome II. Assess the activation status of extracellular signal-regulated kinase (ERK), protein kinase B (Akt) and ribosomal protein S6 kinase (S6K) in tumor biopsy samples at baseline and at the time of progression.
III. Determine the cytokine profile before and after treatment in patients.
OUTLINE: This is a dose-escalation study of binimetinib.
Patients receive binimetinib orally (PO) twice daily (BID) on days 1-21 and docetaxel intravenously (IV) on day 21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who have stable disease or better after completing 6 courses of binimetinib and docetaxel may continue receiving binimetinib PO BID in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then annually for up to 5 years.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase IB Dose Escalation and Expansion Trial of MEK 162 With Docetaxel in Previously Treated Stage IV, Non-small Cell Lung Cancer (NSCLC)|
|Study Start Date :||June 2016|
|Estimated Primary Completion Date :||June 2018|
|Estimated Study Completion Date :||June 2019|
Experimental: Treatment (binimetinib and docetaxel)
Patients receive binimetinib PO BID on days 1-21 and docetaxel IV on day 21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who have stable disease or better after completing 6 courses of binimetinib and docetaxel may continue receiving binimetinib PO BID in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
- Incidence of adverse events, graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.03 [ Time Frame: Up to 30 days post-treatment ]Side effects will be tabulated according to grade and will do sub-analysis based on patient demographic categories such as age and ECOG performance status.
- Incidence of dose-limiting toxicities, graded according to the CTCAE v4.03 [ Time Frame: 21 days ]Side effects will be tabulated according to grade and will do sub-analysis based on patient demographic categories such as age and ECOG performance status.
- Maximum tolerated dose of binimetinib in combination with docetaxel [ Time Frame: 21 days ]
- Biomarker analyses [ Time Frame: Up to 30 days post-treatment ]Will determine if there is a correlation of baseline biomarkers and objective tumor response. For categorical markers will use Fisher's exact test to examine the relationship with response and different categorical variables at specific time points. For quantitative markers will use one-way analysis of variance to compare the marker levels between response categories. Correlations between pairs of quantitative markers will be performed using Pearson correlations if the marker distributions are approximately normal. For non-normality will use the Kendall correlation coefficients.
- Mutations in KRAS and NRAS [ Time Frame: Up to 30 days post-treatment ]Will determine if there is a correlation of response in patients treated with docetaxel and binimetinib with mutations in KRAS and NRAS.
- Objective tumor response rate (the rate of complete response or partial response), as defined by RECIST 1.1 [ Time Frame: Up to 5 years ]The proportion ever achieving a clinical and objective tumor response will be estimated and will construct an exact one-sided 90% confidence interval to identify the likely range for the underlying tumor response rate. Tumor response will be correlated with biomarkers as well as other patient characteristics such as ECOG performance status, k-ras and neuroblastoma RAS viral oncogene homolog (n-ras) mutational status using a variety of analytic techniques.
- Pharmacokinetic (PK) profile will assess binimetinib (MEK162) levels during treatment cycles [ Time Frame: On days 1 and 8 of course 1 and on day 1 of course 2 ]Analyzed by tabulation of PK values with mean and standard deviation at each time point.
- Progression free survival [ Time Frame: Up to 5 years ]Cox-proportional hazards regression models will be used to correlate time to disease progression to both quantitative and categorical variables. Survival distributions will be estimated with the Kaplan-Meier method and significant differences between survival rates will be calculated with the log-rank test.
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): NCT02451865
|United States, California|
|UCLA / Jonsson Comprehensive Cancer Center|
|Los Angeles, California, United States, 90095|
|Principal Investigator:||Edward Garon||UCLA / Jonsson Comprehensive Cancer Center|