Pembrolizumab, Paclitaxel, Carboplatin, and Radiation Therapy in Treating Patients With Stage II-IIIB Non-Small Cell Lung Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02621398|
Recruitment Status : Active, not recruiting
First Posted : December 3, 2015
Last Update Posted : September 23, 2019
|Condition or disease||Intervention/treatment||Phase|
|Stage II Non-Small Cell Lung Cancer Stage IIIA Non-Small Cell Lung Cancer Stage IIIB Non-Small Cell Lung Cancer||Radiation: 3-Dimensional Conformal Radiation Therapy Drug: Carboplatin Radiation: Intensity-Modulated Radiation Therapy Other: Laboratory Biomarker Analysis Drug: Paclitaxel Biological: Pembrolizumab||Phase 1|
I. To assess safety and toxicity of anti-programmed cell death 1 (PD-1) inhibition with pembrolizumab with concurrent chemoradiation therapy for non-operable, locally advanced non-small cell lung cancer.
I. To evaluate local control and distant metastasis-free survival, progression-free and overall survival with the addition of pembrolizumab to chemoradiotherapy.
II. To evaluate the rates of pneumonitis that may result from combination pembrolizumab and chemoradiotherapy.
I. To assess whether programmed cell death ligand 1 (PDL1) status on immunohistochemistry is predictive of response to pembrolizumab when combined with chemoradiation therapy.
II. To assess T cell (cluster of differentiation 8 positive [CD8+] T cells and CD4+ forkhead box P3 positive [FoxP3+] regulatory cells) responses at weeks 1, 3, 6 during chemoradiation therapy and before each administration of pembrolizumab for cycles 1, 2, 3.
OUTLINE: This is a dose-escalation study of pembrolizumab.
Patients receive paclitaxel intravenously (IV) over 1 hour and carboplatin IV over 30 minutes on days 1, 8, 15, 22, 29, and 36. Patients undergo 3-dimensional (3D) conformal radiation therapy (CRT) or intensity-modulated radiation therapy (IMRT) once daily (QD) 5 days a week for 6 weeks . Beginning 2-6 weeks after, 2 weeks before the end, or at the start of chemotherapy and radiation therapy , patients also receive pembrolizumab IV over 30 minutes on day 1. Treatment with pembrolizumab repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days every 12 weeks for 1 year, every 16 weeks for 1 year, every 6 months for 3 years, and then annually thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Moving PD-1 Blockade With Pembrolizumab Into Concurrent Chemoradiation for Locally Advanced Non-Small Cell Lung Cancer|
|Actual Study Start Date :||April 11, 2016|
|Estimated Primary Completion Date :||December 2021|
|Estimated Study Completion Date :||December 2021|
Experimental: Treatment (paclitaxel, carboplatin, radiation, pembrolizumab)
Patients receive paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1, 8, 15, 22, 29, and 36. Patients undergo 3D CRT or IMRT QD 5 days a week for 6 weeks. Beginning 2-6 weeks after, 2 weeks before the end, or at the start of chemotherapy and radiation therapy, patients also receive pembrolizumab IV over 30 minutes on day 1. Treatment with pembrolizumab repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.
Radiation: 3-Dimensional Conformal Radiation Therapy
Undergo 3D-CRT or IMRT
Radiation: Intensity-Modulated Radiation Therapy
Undergo 3D-CRT or IMRT
Other: Laboratory Biomarker Analysis
- Maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of the combination of pembrolizumab with paclitaxel, carboplatin and radiation therapy according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 30 days ]The 3+3 algorithm design will be used to find the MTD. Safety will be evaluated by DLT, defined as grade 4 pneumonitis. Toxicities will be characterized based on seriousness, causality, toxicity grading, and action taken with regard to trial treatment.
- Best overall response according to RECIST 1.1 [ Time Frame: Time from the start of the treatment until disease progression/recurrence, assessed up to 5 years ]Response rates will be compared to historical results.
- Local survival [ Time Frame: Up to 5 years ]
- Metastasis-free survival [ Time Frame: Up to 5 years ]
- Overall survival [ Time Frame: Up to 5 years ]
- Progression free survival according RECIST 1.1 and immune-related Response Evaluation Criteria In Solid Tumors [ Time Frame: Up to 5 years ]
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): NCT02621398
|United States, Connecticut|
|Yale Cancer Center|
|New Haven, Connecticut, United States, 06510|
|United States, New Jersey|
|Rutgers Cancer Institute of New Jersey|
|New Brunswick, New Jersey, United States, 08903|
|United States, Pennsylvania|
|University of Pennsylvania/Abramson Cancer Center|
|Philadelphia, Pennsylvania, United States, 19104|
|Principal Investigator:||Salma Jabbour, MD||Rutgers Cancer Institute of New Jersey|