Selinexor and Docetaxel in Treating Patients With Recurrent or Metastatic Squamous Cell Lung Cancer
|ClinicalTrials.gov Identifier: NCT02536495|
Recruitment Status : Withdrawn (PI decision due to funding support)
First Posted : September 1, 2015
Last Update Posted : October 30, 2015
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Squamous Cell Lung Carcinoma Stage IV Squamous Cell Lung Carcinoma||Drug: Docetaxel Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Selinexor||Phase 1 Phase 2|
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)
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.
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 (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Investigator-Sponsored Phase 1/2 Study of Selinexor (KPT-330) and Docetaxel as Second Line Therapy in Patients With Relapsed Squamous Cell Lung Cancer|
|Study Start Date :||September 2015|
|Estimated Primary Completion Date :||December 2018|
Experimental: Treatment (docetaxel, selinexor)
Patients receive docetaxel IV on day 1 and selinexor PO BID on days 1, 3, 7, 9, 13, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- Progression free survival [ 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 ]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.
- Disease control rate (Complete Response + Partial Response + stable disease) [ Time Frame: Up to 1 year ]An analysis of disease control rate will be performed. These estimates will be accompanied by exact binomial confidence intervals as well.
- Incidence of adverse events, graded according to the National Cancer Institute CTCAE version 4.03 [ Time Frame: Up to 1 year ]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.
- Objective response rate (complete response [CR] or partial response [PR] by RECIST) [ Time Frame: Up to 1 year ]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.
- Overall survival [ 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 ]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.
- Changes in tumor suppressor protein expression levels [ Time Frame: Baseline to up to course 2, day 1 ]Tumor biopsies before and after therapy will be evaluated to assess baseline expression of tumor suppressor proteins and how change in these proteins may correspond with clinical outcomes of interest. Markers will be summarized by descriptive statistics overall and through stratified Kaplan Meier plots to explore differences in PFS. Generalized linear models will model changes in expression levels over time, with potential adjustment for confounding variables.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02536495
|Principal Investigator:||Erin Bertino, MD||Ohio State University Comprehensive Cancer Center|