Renal Cell Carcinoma, Renal Cell Carcinoma Stage IV
Conditions
Brief summary
This single center phase 1 trial will study the combination of nivolumab+ipilimumab with embolization in participants with renal cell carcinoma. The study will evaluate the safety of embolotherapy in patients with metastatic RCC receiving nivolumab+ipilimumab. The hypothesis is that the number of serious adverse events will be no greater than the number of serious adverse events for both therapies combined.
Detailed description
Previously untreated subjects with stage 4 RCC and unresected primary tumor or metastasis amenable to embolization will undergo two cycles of combination immune checkpoint inhibition (ICI) therapy, embolization of the target tumor, then resume ICI therapy. Study ends with safety and efficacy assessment at 6 months. Correlative blood and tissue specimens will be obtained.
Interventions
DRUGNivolumab
Nivolumab 3 mg/kg IV every four weeks, first in combination with capecitabine then alone
DRUGIpilimumab
ipilimumab 1/mg/kg IV every 3 weeks x 4 cycles, in combination with Nivolumab
DEVICEbland embolization
Lipiodol:ethanol embolization of their primary or target tumor
Sponsors
Abramson Cancer Center at Penn Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Metastatic renal cell carcinoma with unresected primary tumor or with metastasis amenable to embolization. 2. No prior immune checkpoint therapy 3. Primary tumor or metastasis amenable to percutaneous embolization per review by the treating interventional oncologist · Patent feeding artery to tumor \> 2 mm diameter without macroscopic arteriovenous fistula/shunt 4. Additional metastatic site \> 1 cm assessable for response by RECIST 1.1 5. Adequate organ function by screening laboratory studies within 30 days of embolization * platelets \> 50K, correctable by transfusion * INR \< 1.5, correctable by transfusion * creatinine \< 2.0 6. ECOG performance status 0-2 7. Age ≥ 18 years 8. Have signed the current approved informed consent form and be willing and able to comply with this protocol 9. Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 5 months after the last dose of study drug 10. Women of childbearing potential must have a negative serum or urine pregnancy test 11. Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose
Exclusion criteria
1. Untreated CNS metastasis 2. Autoimmune disorder; subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment 3. Immunodeficiency syndrome 4. Glucocorticoid (\> 10 mg daily prednisone equivalents) or immunosuppressant therapy 5. Active infection requiring systemic therapy 6. Any other medical or personal condition that, in the opinion of the site investigator, may potentially compromise the safety or compliance of the patient, or may preclude the patient's successful completion of the clinical trial. 7. Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection 8. Contrast allergy not mitigated by usual prophylaxis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of serious adverse events | Serious adverse events will be recorded from time of informed to consent to 100 days after the end of study intervention | SAE rate following embolization in patients |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate | Measured from baseline to 6 months post initiation | Objective response rate by RECIST 1.1 |
| Characterization of immune cells | From baseline to 12 weeks post initiation of therapy | Characterization of tumor-infiltrating leukocytes in primary and metastatic lesions before and after embolotherapy |
| PD-L1 | From baseline to 12 weeks post initiation of therapy | Percentage of PD-L1 stain positivity in the primary tumor biopsy of participants |
Countries
United States
Outcome results
None listed