This is an open label single arm phase 2 clinical trial in patients with metastatic solid malignancy of any histology who have previously experienced limited progression in at least 1 and up to 5 lesions while on immune checkpoint inhibitors monotherapy.
All potential subjects are required to undergo screening evaluation to determine eligibility within 28 days of study enrollment. Eligible subjects will continue the same immune checkpoint inhibitors on which they experienced limited progression and will also receive radiation therapy. radiation therapy for all subjects will consist of treating one tumor of the treating physician's preference, and after a 1-week interval during which immune checkpoint inhibitor is continued alone, radiation therapy will be given to a second and separate tumor. No additional radiation therapy will be delivered. immune checkpoint inhibitors will be continued until disease progression or unacceptable toxicity. Diagnostic imaging studies will be performed to determine treatment response at baseline/screening, 8 weeks after initiation of radiation therapy to the first lesion and every 8 weeks thereafter. Peripheral blood mononuclear cell composition will be evaluated at various time points within 14 days of starting radiation therapy, on Day 8 (1 week after starting radiation therapy to the first lesion), Day 23 (1 week after starting radiation therapy to the second lesion), and 8 weeks after treatment initiation. A total of 52 subjects will be enrolled on this trial. The expected rate of accrual is 2 patients per month at a single institution over 26 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Radiation therapy for all subjects will consist of treating one tumor of the treating physician's preference (40 Gray (Gy) in 5 fractions), and after a 1-week interval during which ICI is continued alone, radiation therapy will be given to a second and separate tumor (30 Gy in 5 fractions).
Miami Cancer Institute at Baptist Health South Florida
Miami, Florida, United States
Change in Overall Response Rate (ORR) According to RECIST 1.1 Criteria
ORR is defined as the percent of participants who have a partial response (PR) or complete response (CR) to therapy of non-irradiated lesions according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria assessed on CT imaging. CR is defined as the disappearance of all target and non-target lesions. PR is defined as at least a 30% decrease from baseline in the sum of the longest diameters of target lesions AND for non-target lesions, no progression of existing lesions or appearance of new lesions.
Time frame: 6 months
Number of Treatment Related Adverse Events
Treatment related adverse events are defined as those possibly, probably, or definitely related to the study treatment. These events will be tabulated and reported by grade of severity.
Time frame: through study completion, an average of 1 year
Change in Immune-related ORR (irORR) According to Immune-related Response Criteria (irRC)
irORR is the percent of patients with best overall response of irCR or irPR from the start of the study until 6 months later. Only index and measurable new lesions are taken into account in irRC and response is defined over at least 4 weeks. irCR is defined as the disappearance of all lesions in two observations at least 4 weeks apart. irPR is defined as at least 50% decrease in tumor burden compared with baseline in two observations at least 4 weeks apart.
Time frame: 6 month
Duration of Response
Duration of response is defined as the time from when CR or PR is first determined until the first date of documented progressive disease (PD) or death, whichever occurs first.
Time frame: 6 month
Overall Survival (OS)
OS is defined as the percent of participants who are alive at the end of the study. Death due to any cause will be considered.
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Time frame: 2 years
Progression-free Survival (PFS)
PFS is defined as the amount of time from first treatment to disease progression or death from any cause.
Time frame: 6 month