This phase I/II trial studies the side effects and best dose of selinexor and docetaxel and to see how well they work when given together in treating patients with squamous cell lung cancer that has come back or spread to other places in the body. Selinexor may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving selinexor together with docetaxel may work better in treating squamous cell lung cancer.
PRIMARY OBJECTIVES: I. To evaluate the toxicity and determine recommended phase II dose of the combination of docetaxel and selinexor. (Phase I) II. To evaluate the efficacy as measured by progression free survival (PFS) of docetaxel and selinexor in patients with recurrent/metastatic squamous cell lung cancer. (Phase I/II) SECONDARY OBJECTIVES: I. To evaluate the objective tumor response rate as determined by radiographic response. II. To evaluated the disease control rate (complete response, partial responses, and stable disease). III. To evaluate the overall survival (OS). IV. To evaluate the safety and tolerability of single agent selinexor. TERTIARY OBJECTIVES: I. Lung cancer genomics sequencing panel. II. Tumor biopsy (baseline and cycle 2). III. Plasma cytokine analysis, peripheral blood ribonucleic acid (RNA) analysis. OUTLINE: This is a phase I, dose-escalation study followed by a phase II study. Patients receive docetaxel intravenously (IV) on day 1 and selinexor orally (PO) twice daily (BID) on days 1, 3, 7, 9, 13, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up monthly for 3 months, every 3 months for 9 months, and then every 6 months thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Progression free survival
PFS will be estimated by the method of Kaplan and Meier (KM). Appropriate one-sided 90% confidence boundary will also be calculated for the final test KM test statistic at 12 weeks.
Time frame: Time from the date of study registration to the date of disease progression or to the date of last observation when no event (disease progression) has occurred, assessed up to 3 years
Disease control rate (Complete Response + Partial Response + stable disease)
An analysis of disease control rate will be performed. These estimates will be accompanied by exact binomial confidence intervals as well.
Time frame: Up to 1 year
Incidence of adverse events, graded according to the National Cancer Institute CTCAE version 4.03
Frequency and severity of adverse events and tolerability of the regimen will be collected and summarized by descriptive statistics for each of the disease cohorts. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.
Time frame: Up to 1 year
Objective response rate (complete response [CR] or partial response [PR] by RECIST)
Those who achieve PR or CR will be considered responses and the overall response rate will be calculated as the number of PRs and CRs divided by the total number of evaluable patients. These estimates will be accompanied by exact binomial confidence intervals as well.
Time frame: Up to 1 year
Overall survival
Kaplan-Meier curves will be used to estimate overall survival. Cox proportional hazards models will be further considered to explore a limited set of confounding factors.
Time frame: Date of study registration to the date of event (i.e., death) or the date of last follow-up if no event has occurred at their last evaluation, assessed up to 3 years
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Given PO