Ignite Creation Date:
2025-12-24 @ 7:58 PM
Ignite Modification Date:
2026-01-02 @ 1:37 AM
Study NCT ID:
NCT03203304
Status:
TERMINATED
Last Update Posted:
2021-06-10
First Post:
2017-06-26
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Stereotactic Body Radiotherapy (SBRT) Followed by Immunotherapy in Liver Cancer
Sponsor:
University of Chicago
Organization:
Study Overview
Official Title:
Phase I Study of Stereotactic Body Radiotherapy (SBRT) Followed by Nivolumab or Ipilimumab With Nivolumab in Unresectable Hepatocellular Carcinoma
Status:
TERMINATED
Status Verified Date:
2021-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Study stopped due to poor accrual.
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
External beam photon stereotactic body radiotherapy (SBRT) using a linear accelerator to a total dose of 40 Gy in 5 fractions delivered once daily with at least 48 hours between each fraction. SBRT treatment will be completed within a 21-day window. Starting within 14 days after completion of SBRT, intravenous nivolumab 240 mg will be given every 2 weeks as monotherapy or in combination with ipilimumab 1 mg/kg IV every 6 weeks.
Detailed Description:
1.1 Primary Objective \& Hypothesis Determine the safety and tolerability of SBRT followed by nivolumab or ipilimumab with nivolumab for hepatocellular carcinoma by establishing the rates of toxicity that occur within 6 months from start of SBRT. Hypothesis: SBRT followed by nivolumab or nivolumab and ipilimumab will have similar toxicity to historical controls of SBRT or nivolumab monotherapy.
1.2 Secondary Objectives and Hypotheses Estimate the investigator determined best overall response rate. Hypothesis: Combining radiation and nivolumab or nivolumab and ipilimumab will improve the best overall response rate compared to historical controls with SBRT or nivolumab alone.
Estimate the rates of long-term adverse events (after 6 months) from the end of SBRT. Hypothesis: Long-term toxicity from SBRT with nivolumab or nivolumab and ipilimumab will be comparable to that observed with nivolumab monotherapy.
Summarize the distant disease control, progression-free survival, and overall survival. Hypothesis: Disease control and survival will be comparable to (or better than) that observed with nivolumab monotherapy.
Summarize the local control of the SBRT treated lesion. Hypothesis: Combining SBRT and nivolumab or nivolumab and ipilimumab will have similar (or better) local control rates as observed in SBRT only series.
1.3 Exploratory Objectives Explore changes in inflammatory biomarkers (including, but not limited to CD8/Treg ratio, total CD4 counts, total lymphocyte count) in pretreatment and on-treatment serially collected peripheral blood samples. Hypothesis: Changes in inflammatory biomarkers after radiation therapy may correlate with a more favorable response to immunotherapy.
Explore changes in the tumor microenvironment induced by radiation on pre and post treatment biopsies. Hypothesis: Changes in the tumor microenvironment after radiation therapy will be observed that may correlate with a more favorable response to immunotherapy.
1.2 Secondary Objectives and Hypotheses Estimate the investigator determined best overall response rate. Hypothesis: Combining radiation and nivolumab or nivolumab and ipilimumab will improve the best overall response rate compared to historical controls with SBRT or nivolumab alone.
Estimate the rates of long-term adverse events (after 6 months) from the end of SBRT. Hypothesis: Long-term toxicity from SBRT with nivolumab or nivolumab and ipilimumab will be comparable to that observed with nivolumab monotherapy.
Summarize the distant disease control, progression-free survival, and overall survival. Hypothesis: Disease control and survival will be comparable to (or better than) that observed with nivolumab monotherapy.
Summarize the local control of the SBRT treated lesion. Hypothesis: Combining SBRT and nivolumab or nivolumab and ipilimumab will have similar (or better) local control rates as observed in SBRT only series.
1.3 Exploratory Objectives Explore changes in inflammatory biomarkers (including, but not limited to CD8/Treg ratio, total CD4 counts, total lymphocyte count) in pretreatment and on-treatment serially collected peripheral blood samples. Hypothesis: Changes in inflammatory biomarkers after radiation therapy may correlate with a more favorable response to immunotherapy.
Explore changes in the tumor microenvironment induced by radiation on pre and post treatment biopsies. Hypothesis: Changes in the tumor microenvironment after radiation therapy will be observed that may correlate with a more favorable response to immunotherapy.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: