Clinical trial NCT04429321: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Renal Cell Carcinoma
Renal Cell Carcinoma Stage IV
Lead sponsor: Abramson Cancer Center at Penn Medicine
Sponsor class: OTHER
First posted: 2020-06-12
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Rate of serious adverse events
timeFrame: Serious adverse events will be recorded from time of informed to consent to 100 days after the end of study intervention
Secondary outcomes:
measure: Objective response rate
timeFrame: Measured from baseline to 6 months post initiation
measure: Characterization of immune cells
timeFrame: From baseline to 12 weeks post initiation of therapy
measure: PD-L1
timeFrame: From baseline to 12 weeks post initiation of therapy
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Michale Soulen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Motzer RJ, Tannir NM, McDermott DF, Aren Frontera O, Melichar B, Choueiri TK, Plimack ER, Barthelemy P, Porta C, George S, Powles T, Donskov F, Neiman V, Kollmannsberger CK, Salman P, Gurney H, Hawkins R, Ravaud A, Grimm MO, Bracarda S, Barrios CH, Tomita Y, Castellano D, Rini BI, Chen AC, Mekan S, McHenry MB, Wind-Rotolo M, Doan J, Sharma P, Hammers HJ, Escudier B; CheckMate 214 Investigators. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med. 2018 Apr 5;378(14):1277-1290. doi: 10.1056/NEJMoa1712126. Epub 2018 Mar 21.
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