Nivolumab + Ipilimumab With Immunostimulatory Embolization for Stage 4 Renal Cell Carcinoma With Unresected Primary

Abramson Cancer Center at Penn Medicine

Status and phase: Terminated; Phase 1

Conditions: Renal Cell Carcinoma Stage IV; Renal Cell Carcinoma

Treatments: Drug: Nivolumab; Drug: Ipilimumab; Device: bland embolization

Study type: Interventional

Funder types: Other

Identifiers

NCT04429321

UPCC 06820

843082 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1 patient

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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1 participants in 1 patient group

Ipilimumab +Nivolumab with Embolization

Experimental group

Description:

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.

Treatment:

Device: bland embolization

Drug: Ipilimumab

Drug: Nivolumab