This study is an open label, multicenter, randomized phase II trial of consolidation immunotherapy with either nivolumab alone or the combination of nivolumab and ipilimumab following concurrent chemoradiation in patients with unresectable stage III NSCLC.
Patients with unresectable stage IIIA or IIIB NSCLC (unresectable as defined by treating physician) will be treated outside this study with concurrent chemoradiation with one of three chemotherapy regimens (cisplatin/etoposide, cisplatin/pemetrexed, or weekly carboplatin/paclitaxel) in addition to standard dose radiation (dosing can range from 59.4 Gy to 66.6 Gy). If repeat imaging between 28-56 days following completion of chemoradiation shows no progressive or metastatic disease, the patients will be eligible for enrollment on the study. Randomization and Stratification: At the time of enrollment, patients will be randomized in a 1:1 fashion to receive either nivolumab 480mg IV every 4 weeks or the combination of nivolumab 3mg/kg IV every 2 weeks with ipilimumab 1mg/kg IV every 6 weeks. Consolidation immunotherapy will be continued until progression or unacceptable toxicity for up to a total of 24 weeks. Subjects will be stratified by stage (IIIA vs. IIIB) and histology (squamous vs. non-squamous). Dose Calculations: Arm 1: The dose of nivolumab will be a fixed dose (not based on subject's weight) at 480mg. Arm 2: The dose of nivolumab will be weight-based at 3mg/kg. The dose of ipilimumab will be weight-based at 1mg/kg. Nivolumab Alone (Arm 1): Arm 1: Nivolumab Administration: Nivolumab 480 mg will be administered as a 60 minute IV infusion on Day 1 of each 28 day cycle. Sites should make every effort to target infusion timing to be as close to 60 minutes as possible. However, given the variability of infusion pumps from site to site, a window of -five minutes and +10 minutes is permitted (i.e., infusion time is 60 minutes: -5 min/+10 min). Treatment will continue for up to 6 cycles, in the absence of prohibitive toxicities or disease progression. Nivolumab Plus Ipilimumab (Arm 2): Arm 2: Nivolumb Administration: Nivolumab 3mg/kg will be administered as a 60 minute IV infusion on Day 1, 15, and 29 of each 42 day cycle. Nivolumab should not be given any earlier than 12 days from the previous dose. Sites should make every effort to target infusion timing to be as close to 60 minutes as possible. However, given the variability of infusion pumps from site to site, a window of -five minutes and +10 minutes is permitted (i.e., infusion time is 60 minutes: -5 min/+10 min). Treatment will continue for up to 4 cycles, in the absence of prohibitive toxicities or disease progression. Arm 2: Ipilimumab Administration: Ipilimumab 1mg/kg will be administered as a 90 minute IV infusion on Day 1 of each 42 day cycle. Sites should make every effort to target infusion timing to be as close to 90 minutes as possible. However, given the variability of infusion pumps from site to site, a window of -five minutes and +10 minutes is permitted (i.e., infusion time is 60 minutes: -5 min/+10 min). Treatment will continue for up to 4 cycles, in the absence of prohibitive toxicities or disease progression. On day 1 of cycle 1, nivolumab will be given first, followed by 30 minutes of monitoring, and then ipilimumab given second, followed by 30 minutes of monitoring. If the subject does not have an infusion reaction during the first cycle, the post-ipilimumab monitoring may be discontinued for subsequent cycles at the discretion of the treating physician. Day 1 monitoring between the nivolumab/ipilimumab infusions will continue throughout all 4 cycles. Post nivolumab monitoring on days 15 and 29 is not mandatory and should follow the guidelines of the local infusion center.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
105
Rush University Medical Center
Chicago, Illinois, United States
University of Illinois Cancer Center
Chicago, Illinois, United States
Indiana University
Indianapolis, Indiana, United States
Progression Free Survival (PFS) at 18-month
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. PFS is defined as the time from randomization until the criteria for disease progression is met as defined by RECIST 1.1 or death as a result of any cause.
Time frame: 18 months
Overall Survival (OS)
Overall survival is defined as the time from randomization until death from any cause.
Time frame: 4 years
Time to Metastatic Disease (TTMD) at 36 Month
TTMD is defined as the time from randomization until evidence of disease outside of the radiated field. The estimate of TTMD at 36 month with 95% confidence interval are reported in the outcome measure data.
Time frame: 36 Months
Number of Participants With Adverse Events
Adverse events will be assessed to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 4.
Time frame: Up to 12 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
University of Louisville James Graham Brown Cancer Center
Louisville, Kentucky, United States
Johns Hopkins Sidney Kimmel Comprehensive
Baltimore, Maryland, United States
Karmanos Cancer Center (Wayne State University)
Detroit, Michigan, United States
Michigan State University
Lansing, Michigan, United States
University of Minnesota
Minneapolis, Minnesota, United States
University of Nebraska Medical Center
Omaha, Nebraska, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
...and 2 more locations