Actively Recruiting
Siltuximab for the Prevention of Severe Immune-Related Adverse Events During Immune Checkpoint Inhibitor Rechallenge in Patients With Advanced Cancer, CIRES Trial
Led by Yuanquan Yang · Updated on 2026-01-20
40
Participants Needed
1
Research Sites
338 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
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 body's 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 body's immune response and reduce inflammation. Giving siltuximab during ICI rechallenge may help prevent severe irAEs in patients with advanced cancer.
CONDITIONS
Official Title
Siltuximab for the Prevention of Severe Immune-Related Adverse Events During Immune Checkpoint Inhibitor Rechallenge in Patients With Advanced Cancer, CIRES Trial
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Males or females aged 18 years or older
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- Patients with advanced cancer types who may benefit from anti-PD1 or anti-PD-L1 therapy rechallenge
- Prior severe immune-related adverse event requiring treatment stop and prednisone over 0.5 mg/kg/day followed by tapering for at least 4 weeks
- Recovery from prior immune adverse events to grade 1 or less
- Taking prednisone 10 mg/day or less (or equivalent)
- Hemoglobin between 7 and 17 g/dL
- Absolute neutrophil count of at least 1000 per mm3
- Platelet count of at least 75 x 10^9/L
- Serum bilirubin no greater than 1.5 times institutional upper limit of normal
- AST and ALT no greater than 3 times institutional upper limit of normal, or 5 times if liver metastases present
- Creatinine clearance of at least 30 mL/min, except patients on hemodialysis
- At least 2 weeks since prior systemic therapy, radiotherapy, or surgery before first study treatment
- Estimated life expectancy of at least 12 weeks
- Negative pregnancy test for those who can bear children
- Willingness to abstain or use highly effective contraception during and 3 months after study
- Not breastfeeding during study and for 3 months after last study dose
- Ability to understand and sign informed consent
You will not qualify if you...
- Women who are pregnant or breastfeeding
- Grade 3 or higher immune-related adverse events where risks outweigh benefits
- Active autoimmune disease or requiring systemic treatment with steroids above 10 mg prednisone daily or other immunosuppressants
- Less than 2 weeks since high dose systemic corticosteroids (prednisone > 0.5 mg/kg/day)
- Concurrent anticancer therapy except palliative radiation and hormone therapy
- Known HIV infection with detectable viral load or CD4 count below 300/mL in past 3 months
- Detectable hepatitis B or C viral load if history of active infection
- High risk for bowel perforation such as severe diverticulitis or active ulcers
- Solid organ transplant (except corneal transplant older than 3 months) or allogeneic bone marrow or stem cell transplant
- Uncontrolled serious illnesses like severe heart failure, recent heart attack, uncontrolled arrhythmia or seizures, or severe hypertension
- Current severe infection
- Allergies or intolerance to monoclonal antibodies or related proteins
- Prior failure of interleukin-6 or its receptor targeted therapies
- Use of any investigational drug within 30 days before study start
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 1 location
1
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210
Actively Recruiting
Research Team
T
The Ohio State University Comprehensive Cancer Cener
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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