Ignite Creation Date:
2024-07-17 @ 11:33 AM
Last Modification Date:
2024-10-26 @ 3:32 PM
Study NCT ID:
NCT06470971
Status:
RECRUITING
Last Update Posted:
2024-07-03
First Post:
2024-06-17
Brief Title:
Siltuximab for the Prevention of Severe Immune-Related Adverse Events During Immune Checkpoint Inhibitor Rechallenge in Patients With Advanced Cancer CIRES Trial
Sponsor:
Yuanquan Yang
Organization:
Ohio State University Comprehensive Cancer Center
Study Overview
Official Title:
Immune Checkpoint Inhibitor Rechallenge in Combination With Siltuximab Prophylaxis for Patients Who Had Prior Immune-Related Adverse Event CIRES Trial
Status:
RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase II trial studies how well giving siltuximab during the reintroduction rechallenge of immune checkpoint inhibitor ICI therapy works in preventing severe immune-related adverse events irAEs in patients with cancer that may have spread from where it first started to nearby tissue lymph nodes or distant parts of the body advanced Immune checkpoint inhibitors such as anti-PD1 and anti-PD-L1 monoclonal antibodies may help the bodys immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread The use of ICI therapy may lead to severe irAEs that can affect essentially any organ system in the body Severe irAEs may lead to the early stopping of life saving treatment Most patients that stop ICI therapy early will eventually progress and require additional treatment Sometimes the decision is made to rechallenge with ICI therapy Many patients who developed severe irAEs during initial ICI therapy are at risk for developing severe irAEs again during the rechallenge Siltuximab is a monoclonal antibody that binds to receptors for a protein called interleukin-6 IL-6 This may help lower the bodys immune response and reduce inflammation Giving siltuximab during ICI rechallenge may help prevent severe irAEs in patients with advanced cancer
Detailed Description:
PRIMARY OBJECTIVE
I To determine whether siltuximab prophylaxis reduces rates of de novo or recurrent severe irAE within 24 weeks of anti-PD-1PD-L1 therapy rechallenge
SECONDARY OBJECTIVE
I To assess the preliminary anti-tumor activity of this combination including overall response rate ORR progression-free survival PFS and overall survival OS
EXPLORATORY OBJECTIVES
I To evaluate potential predictive biomarkers such as baseline serum IL-6 level C-reactive protein CRP suppression level tissue IL-6 expression stool microbiome and antibody clearance rate
II To assess changes in immune cell infiltration of irAE site pre- and post-treatment by multiomics profiling
III To assess patient-reported outcomes by Patient-Reported Outcomes Measurement Information System PROMIS instruments
IV To correlate circulating tumor deoxyribonucleic acid ctDNA levels with treatment responses
OUTLINE
Patients receive anti-PD1 or anti-PD-L1 monoclonal antibody therapy either every 3 or 6 weeks or every 2 or 4 weeks per physicians choice Patients also receive siltuximab intravenously IV over 1 hour on day 1 of each cycle prior to the administration of anti-PD1 or anti-PD-L1 therapy Treatment repeats either every 3 weeks for up to 8 doses or every 4 weeks for up to 6 doses in the absence of disease progression or unacceptable toxicity Patients may undergo biopsy and bone scan on study as well as blood sample collection and computed tomography CT or magnetic resonance imaging MRI throughout the study
After completion of study treatment patients are followed up at day 28 every 12 weeks for up to 2 years and then every 6 months until 5 years following registration
I To determine whether siltuximab prophylaxis reduces rates of de novo or recurrent severe irAE within 24 weeks of anti-PD-1PD-L1 therapy rechallenge
SECONDARY OBJECTIVE
I To assess the preliminary anti-tumor activity of this combination including overall response rate ORR progression-free survival PFS and overall survival OS
EXPLORATORY OBJECTIVES
I To evaluate potential predictive biomarkers such as baseline serum IL-6 level C-reactive protein CRP suppression level tissue IL-6 expression stool microbiome and antibody clearance rate
II To assess changes in immune cell infiltration of irAE site pre- and post-treatment by multiomics profiling
III To assess patient-reported outcomes by Patient-Reported Outcomes Measurement Information System PROMIS instruments
IV To correlate circulating tumor deoxyribonucleic acid ctDNA levels with treatment responses
OUTLINE
Patients receive anti-PD1 or anti-PD-L1 monoclonal antibody therapy either every 3 or 6 weeks or every 2 or 4 weeks per physicians choice Patients also receive siltuximab intravenously IV over 1 hour on day 1 of each cycle prior to the administration of anti-PD1 or anti-PD-L1 therapy Treatment repeats either every 3 weeks for up to 8 doses or every 4 weeks for up to 6 doses in the absence of disease progression or unacceptable toxicity Patients may undergo biopsy and bone scan on study as well as blood sample collection and computed tomography CT or magnetic resonance imaging MRI throughout the study
After completion of study treatment patients are followed up at day 28 every 12 weeks for up to 2 years and then every 6 months until 5 years following registration
Study Oversight
Has Oversight DMC:
None
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?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2024-04853 | REGISTRY | None | None |