The purpose of this study is to test a new way of treating the most common form of lung cancer. The investigators are testing a combination of radiotherapy with two new forms of immunotherapy. This study is testing the safety and effectiveness of this treatment approach as compared to standard treatment options.
This is a randomized, open-label phase I/II study. Subjects will be randomized in a 1:1 ratio to receive FLT3 ligand (CDX-301), anti-CD40 antibody (CDX-1140) and SBRT (Arm 1) versus standard care (Arm 2). Subjects on either study arm with limited disease will receive SBRT to all evident sites of active disease. Subjects on Arm 1 with extensive disease will initially receive SBRT to a single site of disease but may receive additional "cycles" of FLT3 ligand (CDX-301) anti-CD40 antibody (CDX-1140), and SBRT at later time points. Subjects on Arm 2 with extensive disease are expected to receive some form of standard systemic therapy (e.g., docetaxel). Subjects on Arm 2 with limited disease may also receive standard systemic therapy following completion of SBRT to all sites of evident disease, at the discretion of the treating physicians. All subjects will be followed closely for treatment-related toxicities. Whole-body PET/CT and CT imaging will be performed prior to study entry, and restaging CT will be performed every 8 weeks thereafter. In the phase I component of this study, subjects will be randomized between study arms until 6 subjects have been randomized to Arm 1. Study accrual will then be halted until 8 weeks after the last study subject begins treatment. If the pre-specified safety criteria are achieved in the Phase I portion of this study, the study will proceed to phase II. The total sample size (Phase I and Phase II) will be 46 subjects. All 46 subjects will be included in efficacy analyses. If the pre-specified safety criteria are not achieved in the Phase I portion of this study, the investigators and Celldex will review safety data from this trial as well as other trials using CDX-301 and CDX-1140 and determine if the experimental treatment regimen should be altered (e.g., by reducing the CDX-1140 dose). The study protocol would be amended accordingly, and Phase I component with the new treatment regimen would be added.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
5
Fms-like tyrosine kinase 3 (FLT3) ligand is a potent hematopoietic growth factor that mobilizes stem cells and greatly increases the number of circulating dendritic cells (DCs) in blood and organs.
CD40 is a key molecule in the regulation of immune responses whose activity can be modulated using antibodies. CD40 is a tumor necrosis factor receptor superfamily member expressed on antigen presenting cells, including dendritic cells, as well as a host of other cell types, including a wide range of tumor cells
For subjects on Arm 1, SBRT will be delivered concurrently with FLT3 ligand during Week 1 of study therapy. If only one lesion is being treated, SBRT should be completed during week 1 (e.g., with daily treatments for a 5-fraction course of treatments every other day for a 3-fraction course). In cases where multiple lesions are being treated with SBRT (Arm 1 or Arm 2) or if treatment is interrupted due to technical issues or intercurrent illness, SBRT may extend beyond Week 1.
Albert Einstein College of Medicine
The Bronx, New York, United States
Phase I: Dose-limiting Toxicity (DLT), Defined as Follows:
Death Any ≥ Grade 3 non-hematological toxicity, with the following exceptions: Grade 3 alopecia, vitiligo, or endocrinopathies controlled by hormone replacement therapy Grade 3 nausea that resolves to ≤ grade 2 with or without treatment within 72 hours Grade 3 vomiting and diarrhea that resolves to ≤ grade 2 with or without treatment within 72 hours Grade 3 fatigue that resolves to ≤ grade 2 within 5 days Grade 3 hypertension in the absence of maximal medical therapy Grade 3 adverse event of tumor flare (defined as local pain, irritation, or rash localized at sites of known or suspected tumor) of ≤ 7 days in duration Grade 3 amylase or lipase abnormalities that are not associated with symptoms or clinical manifestations of pancreatitis. It is recommended to consult with the Principal Investigator for grade 4 amylase or lipase abnormalities Grade 3 clinically significant laboratory abnormalities that are asymptomatic and can be reversed within 72 hours, however: Any Grade 4
Time frame: up to 8 weeks after initiation of study therapy
Phase II: Progression-free Survival (PFS) Duration
Time frame: defined as time from study registration until disease progression (scored using iRECIST) or death, whichever comes first up to 51 weeks.
Overall Survival (OS) Duration
Length of time that patient survives from time of study registration
Time frame: From date of registration until the date of death from any cause, assessed up to 2 years
Radiographic Responses Using Descriptive Statistics
The clinical benefit rate (CBR) will be defined as the percentage of subjects who achieve best response of confirmed CR or PR, or stable disease (SD) for at least four months.
Time frame: From date of registration, assessed up to 4 months
Quality of Life Using EORTC QLQ-LC13 (Quality of Life Questionnaire, Lung Cancer)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Summary statistics (mean, standard deviation, median, 25th and 75th percentiles, and range) and the mean change from baseline of linear-transformed scores will be reported for all the items and subscales of the EORTC QLQ-C30 questionnaire and the QLQ-LC13, according to the EORTC scoring manual guidelines. higher scores are a better level of functioning
Time frame: 1 year
Quality of Life Using QLQ-C30 (Quality of Life Questionnaire)
Summary statistics (mean, standard deviation, median, 25th and 75th percentiles, and range) and the mean change from baseline of linear-transformed scores will be reported for all the items and subscales of the EORTC QLQ-C30 questionnaire and the QLQ-LC13, according to the EORTC scoring manual guidelines. Most items are scored 1 to 4, higher scores are a better level of functioning.
Time frame: 1 year
Daily Step Count Using Descriptive Statistics
Average daily step counts
Time frame: 1 year