Nivolumab in Treating Patients With Advanced Metastatic Non-small Cell Lung Cancer
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|ClinicalTrials.gov Identifier: NCT03121417|
Recruitment Status : Withdrawn (Slow accrual)
First Posted : April 20, 2017
Last Update Posted : May 21, 2019
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Non-Small Cell Lung Carcinoma Stage IV Non-Small Cell Lung Cancer||Biological: Nivolumab||Phase 2|
I. To study the sustained proliferation of programmed cell death protein (PD)-1+Ki-67+cluster of differentiation(CD)8 T cells as a predictive biomarker of response to nivolumab by comparing the response rates to nivolumab treatment between two groups of patients (positive vs negative) stratified by the status of PD-1+Ki-67+CD8 T cells.
I. Characterize phenotype of proliferating T cells in peripheral blood in the setting of nivolumab therapy.
II. Perform gene expression profiling of activated T cells from peripheral blood.
III. Perform T cell receptor (TCR) sequencing of activated T cells from peripheral blood and tumor infiltrating T cells (TILs).
IV. Assess pre-treatment biopsies and biopsies at the time of disease progression for tumor infiltrating lymphocytes.
V. Determine progression free survival (PFS) and overall survival (OS).
Patients receive nivolumab intravenously (IV) over 30 minutes on day 1. Courses repeat every 2 weeks in the absence of disease progression or unexpected toxicity.
After completion of study treatment, patients are followed up at 30 and 90 days and then every 3 months for up to 3 years.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Biomarker-Driven Phase 2 Study of Nivolumab in Advanced Metastatic NSCLC|
|Actual Study Start Date :||July 21, 2017|
|Actual Primary Completion Date :||March 9, 2019|
|Actual Study Completion Date :||March 9, 2019|
Experimental: Treatment (nivolumab)
Patients receive nivolumab IV over 30 minutes on day 1. Courses repeat every 2 weeks in the absence of disease progression or unexpected toxicity
240 mg given IV
- Objective response rate (ORR) [ Time Frame: Up to 3 years after study start ]The response rates to nivolumab treatment will be compared between two groups of patients (positive vs negative) stratified by the status of PD-1+Ki-67+CD8 T cells. The objective disease response (ORR) is determined radiographically by Response Criteria in Solid Tumors version 1.1 (RECIST 1.1).
- Change in T cell population in the peripheral blood assessed by flow cytometry [ Time Frame: Baseline up to 16 weeks after study start ]Fresh or frozen peripheral blood mononuclear cells (PBMCs) will be stained with anti-cluster of differentiation(CD)8, -CD4, -CD3, -CD45RA, -CC-chemokine receptor 7 (CCR7), -PD-1, -human leukocyte antigen(HLA)-antigen D related(DR), -CD38, -inducible co-stimulator(ICOS), -CD28, -CD27, -CD127, and -Tim-3. Live/Dead cell discrimination will be performed using fixable Dead Cell Stain Kit (Life Technologies). Samples will be acquired with LSR II flow cytometer (BD Biosciences) and analyzed using FlowJo software (Tree Star).
- Progression Free Survival (PFS) [ Time Frame: Every 12 weeks until disease progression or up to 3 years ]Patients will have tumor assessments per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 at 6 weeks (±1 week) following initiation of registration and treatment. Subsequent tumor assessments should occur every 6 weeks (±1 week) up to week 49, then every 12 weeks until disease progression. Patients will also have ongoing evaluation of peripheral blood immune cell populations and cytokines that will be analyzed and correlated with each restaging scan.
- Overall survival (OS) [ Time Frame: Every 3 months up to 3 years after drug discontinuation ]Patients who discontinue treatment with nivolumab on this protocol will be followed for survival follow-up data until death or conclusion of the study. They will be contacted every 3 months by telephone for survival follow-up.
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): NCT03121417
|United States, Georgia|
|Emory University Hospital Midtown|
|Atlanta, Georgia, United States, 30308|
|Emory University/Winship Cancer Institute|
|Atlanta, Georgia, United States, 30322|
|Principal Investigator:||Rathi Pillai, MD||Emory University|