This is an open label, multi-institutional, single arm phase II trial of consolidation therapy with pembrolizumab, following initial treatment with concurrent chemoradiation in patients with inoperable or unresectable stage IIIA or IIIB NSCLC. No randomization or blinding is involved.
OUTLINE: This is a multi-center study. Eligible patients must have completed concurrent chemoradiation with a standard chemotherapy regimen (either cisplatin/etoposide or carboplatin/paclitaxel) and a dose of radiation ranging from 59.4-66.6Gy, with restaging completed 28 days to 56 days post-chemoradiation. Patients with progressive disease will not be eligible for investigational treatment. Patients with stable disease/response will be eligible to register for investigational treatment of consolidation therapy to begin a minimum of 28 days and a maximum of 56 days from completion of chemoradiotherapy. INVESTIGATIONAL TREATMENT: Pembrolizumab, 200 mg IV every 3 weeks (until progressive disease (PD), unacceptable toxicity, or after 12 months (52 weeks) of therapy with pembrolizumab. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Hematopoietic: * Absolute neutrophil count (ANC) ≥1,500/mcL * Platelets ≥100,000/mcL * Hemoglobin ≥9 g/dL or ≥5.6 mmol/L Renal: * Serum creatinine OR measured or calculated creatinine clearance ≤1.5 X institutional upper limit of normal (ULN) OR ≥60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN (glomerular filtration rate (GFR) can also be used in place of creatinine or CrCl) Hepatic: * Serum total bilirubin ≤ 1.5 X institutional ULN OR direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 institutional ULN * Aspartate transaminase (AST), serum glutamic oxaloacetic transaminase (SGOT), alanine transaminase (ALT), serum glutamic pyruvic transaminase (SGPT) ≤ 2.5 X institutional ULN Coagulation: * International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X institutional ULN unless subject is receiving anticoagulant therapy as long as PT/INR/PTT is within therapeutic range of intended use of anticoagulants.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
93
Pembrolizumab, 200 mg IV every 3 weeks (until PD, unacceptable toxicity, or after 12 months of therapy with pembrolizumab.
City of Hope Comprehensive Cancer Center
Duarte, California, United States
Fort Wayne Oncology & Hematology, Inc.
Fort Wayne, Indiana, United States
Time to Death or Distant Metastasis
Time to Death or Distant Metastasis is defined as the time from the date of randomization until the first date of distant metastasis or death in the absence of distant metastasis. Distant metastasis is defined as any new lesion that was outside of the radiation field according to RECIST 1.1 or proven by biopsy. The Primary objective in the study was to determine if consolidation therapy with pembrolizumab following concurrent chemoradiation improves time to death or distant metastatic disease, depending on which occurs first, in subjects with inoperable or unresectable stage IIIA or IIIB NSCLC.
Time frame: From start of treatment until death or distant metastasis (estimate 18 months) up to a maximum of 47 months.
Progression Free Survival
Progression Free Survival is defined as the time from randomization until the date of objective disease progression (RECIST 1.1) or death (by any cause in the absence of progression). Progression is defined using RECIST 1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. One of the secondary objectives in the study is to determine if consolidation therapy with pembrolizumab following concurrent chemoradiation improves progression free survival in subjects with inoperable or unresectable stage IIA or IIIB non-small cell lung cancer(NSCLC). PFS has been estimated by Kaplan-Meier method.
Time frame: From start of treatment until Progression based on RECIST 1.1 or death up to a maximum value of 47 months
Overall Survival
Overall Survival is defined as the time from the date of randomization until death due to any cause. One of the secondary objectives in the study is to determine if consolidation therapy with pembrolizumab following concurrent chemoradiation improves Overall Survival in subjects with inoperable or unresectable stage IIA or IIIB non-small cell lung cancer(NSCLC). OS has been estimated by Kaplan-Meier method.
Time frame: From the date of randomization up to a maximum value of 47 months or death.
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IU Health Goshen Hospital
Goshen, Indiana, United States
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States
IU Health Central Indiana Cancer Centers
Indianapolis, Indiana, United States
Community Regional Cancer Care
Indianapolis, Indiana, United States
IU Health Arnett Cancer Center
Lafayette, Indiana, United States
Horizon Oncology Research, Inc.
Lafayette, Indiana, United States
IU Health at Ball Memorial Hospital
Muncie, Indiana, United States
Oncology Hematology Associates of SW Indiana
Newburgh, Indiana, United States
...and 5 more locations
Number of Participants Experiencing Grade 3-4 AE With Adverse Events as a Measure of Safety and Tolerability
One of the secondary objective in this study is to assess toxicity and tolerability of pembrolizumab consolidation therapy following concurrent chemoradiation in subjects with stage IIIA or IIIB NSCLC.
Time frame: From the time of consent until 30 days after last dose of pembrolizumab up to a maximumof 18 months.