The purpose of this study is to find out if having radiation therapy and continuing immunotherapy can improve the benefit of immunotherapy. There have been reports of patients who were treated with radiation therapy that not only caused the treated tumors to shrink or stop growing, but also resulted in tumors that had not been treated in other parts of the body to shrink or stop growing. This effect is thought to be brought about by cells in the body's immune system that become active as a result of the effects of radiation therapy. If radiation therapy can stimulate the immune system, it may be possible for immunotherapy to be helpful again in treating a cancer that the immunotherapy drug helped treat before. This study will also check if receiving immunotherapy at the end of radiation therapy has any effect on the side effects of radiation therapy or immunotherapy.
Stereotactic radiotherapy (SRT) will be delivered in up to 10 treatment fractions over 1 to 2 weeks. Patients will continue to receive the same FDA-approved programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor that they had been receiving at the time of disease progression through 52 weeks following completion of SRT. Correlative blood samples will be collected at baseline, prior to the second SRT fraction, after the last SRT fraction (on the same day), and at 8, 24, and 52 weeks after the last SRT fraction. These samples will be used to determine the mechanistic immunologic effects of therapy.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
5
Treatment will be planned to deliver a total of 18 to 60 Gy to the planning target volume (PTV) in 3 to 5 fractions over 1 to 2 weeks.
Standard of Care - patient will continue to be given the same PD-1 inhibitor they were receiving prior to study registration
Standard of Care - patient will continue to be given the same PD-L1 inhibitor they were receiving prior to study registration
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, United States
Number of Patients With Improved Disease Control
1. Number of patients with improved disease control at 24 weeks following RT \[Time Frame: up to 24 weeks following RT\] 1a. Number of participants with improved disease control (SD, PR or CR) at 24 weeks per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) 1b. For participants enrolled with brain metastases: number of participants with improved disease (SD, PR or CR) control at 24 weeks per per Response Assessment in Neuro-Oncology for Brain Metastases (RANO-BM)
Time frame: Up to 24 weeks following SRT
Number of Patients Alive and Free From Progression at 24 Weeks Following SRT Per Unidimensional Immune-related Response Criteria (irRC)
Number of participants alive and without progression (irSD+irPR+irCR) at 24 weeks post-RT per unidimensional immune-related response criteria (irRC) 1b. For participants enrolled with brain metastases: number of participants alive and without progression (SD+PR+CR) at 24 weeks post-RT per immune Response Assessment in Neuro-Oncology (iRANO)
Time frame: Up to 24 weeks following SRT
Number of Participants With Treatment Response in Irradiated Tumor Sites
Number of participants with treatment response in irradiated tumor sites at 24 weeks post-RT.
Time frame: Up to 24 weeks following SRT
Number of Participants With Treatment Response in Non-irradiated Tumor Sites
Number of participants with treatment response in non-irradiated tumor sites at 24 weeks post-RT
Time frame: Up to 24 weeks post-RT
Number of Patients Alive
Number of patients who are alive at 2 years after completion of SRT
Time frame: 2 years following SRT
Number of Participants With Grade 3 or Greater Toxicity
Number of participants with grade 3 or greater toxicity from the regimen through 8 weeks following RT
Time frame: Through 8 weeks following SRT
Number of Participants With Immune-related Toxicity From the Regimen
Number participants with immune-related AEs (irAEs) that require both checkpoint-inhibitor discontinuation and initiation of steroids reported per CTCAE v5.0
Time frame: Up to 2 years following RT
Radiobiological Signatures Associated With the Regimen
Number participants with samples collected and number of participants with samples analyzed for immunologic effects of the regimen
Time frame: Up to 52 weeks post SRT
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