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

Renal Cell Carcinoma Clinical Trial

Official title:

UPCC06820 Phase 1 Trial of Nivolumab + Ipilimumab With Immunostimulatory Embolization for Stage 4 Renal Cell Carcinoma With Unresected Primary

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04429321
• Other study ID #: UPCC 06820
• Secondary ID: 843082
• Status: Terminated
• Phase: Phase 1
• Start date: August 26, 2020
• Est. completion date: January 31, 2024

Study information

• Verified date: April 2024
• Source: Abramson Cancer Center at Penn Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: January 31, 2024
• Est. primary completion date: January 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Renal Cell Carcinoma
• Renal Cell Carcinoma Stage IV

Intervention

Drug:
• Nivolumab
Nivolumab 3 mg/kg IV every four weeks, first in combination with capecitabine then alone
• Ipilimumab
ipilimumab 1/mg/kg IV every 3 weeks x 4 cycles, in combination with Nivolumab

Device:
• bland embolization
Lipiodol:ethanol embolization of their primary or target tumor

Locations

Country	Name	City	State
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Abramson Cancer Center at Penn Medicine

Country where clinical trial is conducted

United States, 

References & Publications (7)

den Brok MH, Sutmuller RP, Nierkens S, Bennink EJ, Frielink C, Toonen LW, Boerman OC, Figdor CG, Ruers TJ, Adema GJ. Efficient loading of dendritic cells following cryo and radiofrequency ablation in combination with immune modulation induces anti-tumour immunity. Br J Cancer. 2006 Oct 9;95(7):896-905. doi: 10.1038/sj.bjc.6603341. Epub 2006 Sep 5. — View Citation

Kato T, Iwasaki T, Uemura M, Nagahara A, Higashihara H, Osuga K, Ikeda Y, Kiyotani K, Park JH, Nonomura N, Nakamura Y. Characterization of the cryoablation-induced immune response in kidney cancer patients. Oncoimmunology. 2017 May 16;6(7):e1326441. doi: 10.1080/2162402X.2017.1326441. eCollection 2017. — View Citation

Mehta A, Oklu R, Sheth RA. Thermal Ablative Therapies and Immune Checkpoint Modulation: Can Locoregional Approaches Effect a Systemic Response? Gastroenterol Res Pract. 2016;2016:9251375. doi: 10.1155/2016/9251375. Epub 2016 Mar 8. — View 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. — View Citation

Sabel MS. Cryo-immunology: a review of the literature and proposed mechanisms for stimulatory versus suppressive immune responses. Cryobiology. 2009 Feb;58(1):1-11. doi: 10.1016/j.cryobiol.2008.10.126. Epub 2008 Oct 17. — View Citation

Swanson DA, Wallace S. Surgery of metastatic renal cell carcinoma and use of renal infarction. Semin Surg Oncol. 1988;4(2):124-8. — View Citation

Zielinski H, Szmigielski S, Petrovich Z. Comparison of preoperative embolization followed by radical nephrectomy with radical nephrectomy alone for renal cell carcinoma. Am J Clin Oncol. 2000 Feb;23(1):6-12. doi: 10.1097/00000421-200002000-00002. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of serious adverse events	SAE rate following embolization in patients	Serious adverse events will be recorded from time of informed to consent to 100 days after the end of study intervention
Secondary	Objective response rate	Objective response rate by RECIST 1.1	Measured from baseline to 6 months post initiation
Secondary	Characterization of immune cells	Characterization of tumor-infiltrating leukocytes in primary and metastatic lesions before and after embolotherapy	From baseline to 12 weeks post initiation of therapy
Secondary	PD-L1	Percentage of PD-L1 stain positivity in the primary tumor biopsy of participants	From baseline to 12 weeks post initiation of therapy