Description:
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.
Title
- Brief Title: Nivolumab + Ipilimumab With Immunostimulatory Embolization for Stage 4 Renal Cell Carcinoma With Unresected Primary
- Official Title: UPCC06820 Phase 1 Trial of Nivolumab + Ipilimumab With Immunostimulatory Embolization for Stage 4 Renal Cell Carcinoma With Unresected Primary
Clinical Trial IDs
- ORG STUDY ID:
UPCC 06820
- SECONDARY ID:
843082
- NCT ID:
NCT04429321
Conditions
- Renal Cell Carcinoma
- Renal Cell Carcinoma Stage IV
Interventions
Drug | Synonyms | Arms |
---|
Nivolumab | Opdivo | Ipilimumab +Nivolumab with Embolization |
Ipilimumab | Yervoy | Ipilimumab +Nivolumab with Embolization |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Ipilimumab +Nivolumab with Embolization | Experimental | Patients initiate ICI therapy with Nivolumab 3 mg/kg + ipilimumab 1/mg/kg IV every 3 weeks x 4 cycles, followed by nivolumab 480mg flat dose IV every four weeks for a total of 6 months of therapy unless stopped for confirmed progression or intolerable toxicities.
Patients will receive 2 cycles of systemic therapy followed by embolization of their primary tumor or metastatic lesion(s) and continue systemic therapy subsequently. | |
Eligibility Criteria
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Rate of serious adverse events |
Time Frame: | Serious adverse events will be recorded from time of informed to consent to 100 days after the end of study intervention |
Safety Issue: | |
Description: | SAE rate following embolization in patients |
Secondary Outcome Measures
Measure: | Objective response rate |
Time Frame: | Measured from baseline to 6 months post initiation |
Safety Issue: | |
Description: | Objective response rate by RECIST 1.1 |
Measure: | Characterization of immune cells |
Time Frame: | From baseline to 12 weeks post initiation of therapy |
Safety Issue: | |
Description: | Characterization of tumor-infiltrating leukocytes in primary and metastatic lesions before and after embolotherapy |
Measure: | PD-L1 |
Time Frame: | From baseline to 12 weeks post initiation of therapy |
Safety Issue: | |
Description: | Percentage of PD-L1 stain positivity in the primary tumor biopsy of participants |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Abramson Cancer Center of the University of Pennsylvania |
Last Updated
January 22, 2021