Building upon the clinical experience of the investigators with the magnetic resonance (MR)-guided radiation therapy system and applying principals of hypofractionation toward the current treatment paradigm of concurrent chemoradiation and consolidation immunotherapy for locally advanced non-small cell lung cancer (NSCLC), this prospective, single-arm Phase II clinical trial with safety lead-in will test the feasibility and outcomes of this approach.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
26
-Radiation will be delivered by this machine
-60Gy in 15 fractions
-50 mg/m\^2 intravenous
-2 mg/mL/min intravenous over 30 minutes
-10 mg/kg
Washington University School of Medicine
St Louis, Missouri, United States
Safety lead-in only: Number of participants with dose limiting toxicities (DLTs)
* Safety of hypofractionated MRI-guided adaptive radiotherapy (60Gy/15 fractions) with concurrent chemotherapy (carboplatin and paclitaxel) and consolidation durvalumab is defined as \<2/6 participants experiencing dose limiting toxicities * DLT is defined as any possibly, probably, or definitely related to concurrent chemoradiation grade 3 toxicity that cannot be managed with maximal supportive care within 2 weeks, or any grade \> 4 toxicity that occurs during treatment * The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for all toxicity reporting.
Time frame: Through 6 months after completion of concurrent chemoradiation (estimated to be 6 months and 3 weeks)
Local control rate (Phase II only)
-Clinical and/or radiographic evidence of progression of disease at the primary (local) site
Time frame: Through 2 years after start of chemoradiation (estimated to be 2 years and 3 weeks)
Regional control rate (Phase II only)
-Clinical and/or radiographic evidence of progression of disease at the previously involved or uninvolved hilar and/or mediastinal nodal (regional) sites
Time frame: Through 2 years after start of chemoradiation (estimated to be 2 years and 3 weeks)
Number of acute toxicities
-Only those that are considered possibly/probably/definitely related to radiation therapy or chemoradiation
Time frame: From start of chemoradiation through 60 days
Number of late toxicities
-Only those that are considered possibly/probably/definitely related to radiation therapy or chemoradiation
Time frame: From 61 days after start of chemoradiation through 2 years after the start of chemoradiation
Tumor response rate
-Tumor response is defined as achieving a partial or complete response per RECIST criteria.
Time frame: Through completion of treatment (estimated to be 12 months and 3 weeks)
Distant recurrence rate
-Distant recurrence is defined as development of metastatic, non-local, and non-regional disease.
Time frame: Through 2 years after start of chemoradiation (estimated to be 2 years and 3 weeks)
Incidence of brain metastases
-Defined as development of brain metastasis.
Time frame: Through 2 years after start of chemoradiation (estimated to be 2 years and 3 weeks)
Progression-free survival (PFS)
* Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). * PFS is defined as survival with no evidence of disease progression (local, regional, or distant) or death
Time frame: Through 2 years after start of chemoradiation (estimated to be 2 years and 3 weeks)
Disease-free survival
Disease-free survival is defined as survival with no evidence of recurrent (local, regional or distant) disease or death
Time frame: Through 2 years after start of chemoradiation (estimated to be 2 years and 3 weeks)
Overall survival
-Defined as survival with no evidence of death.
Time frame: Through 2 years after start of chemoradiation (estimated to be 2 years and 3 weeks)
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