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

NCT04429321 | Terminated Phase 1 FDA Drug FDA Device

• 2 other identifiers: UPCC 06820843082
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Renal Cell Carcinoma; Renal Cell Carcinoma Stage IV

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Objective response rate

  Measured from baseline to 6 months post initiation

• Characterization of immune cells

  From baseline to 12 weeks post initiation of therapy

• PD-L1

  From baseline to 12 weeks post initiation of therapy

Study Arms (1)

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.

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

Interventions

Nivolumab DRUG

Nivolumab 3 mg/kg IV every four weeks, first in combination with capecitabine then alone

Also known as: Opdivo

Ipilimumab +Nivolumab with Embolization

Ipilimumab DRUG

ipilimumab 1/mg/kg IV every 3 weeks x 4 cycles, in combination with Nivolumab

Also known as: Yervoy

Ipilimumab +Nivolumab with Embolization

bland embolization DEVICE

Lipiodol:ethanol embolization of their primary or target tumor

Also known as: trans-arterial embolization

Ipilimumab +Nivolumab with Embolization

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Metastatic renal cell carcinoma with unresected primary tumor or with metastasis amenable to embolization.
• No prior immune checkpoint therapy
• 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
• Additional metastatic site \> 1 cm assessable for response by RECIST 1.1
• 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
• ECOG performance status 0-2
• Age ≥ 18 years
• Have signed the current approved informed consent form and be willing and able to comply with this protocol
• 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
• Women of childbearing potential must have a negative serum or urine pregnancy test
• 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

You may not qualify if:

• Untreated CNS metastasis
• 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
• Immunodeficiency syndrome
• Glucocorticoid (\> 10 mg daily prednisone equivalents) or immunosuppressant therapy
• Active infection requiring systemic therapy
• 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.
• Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
• Contrast allergy not mitigated by usual prophylaxis

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead

Study Sites (1)

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (7)

• 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.

  PMID: 29562145 BACKGROUND

• 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.

  PMID: 10683065 BACKGROUND

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

  PMID: 3293153 BACKGROUND

• 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.

  PMID: 19007768 BACKGROUND

• 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.

  PMID: 16953240 BACKGROUND

• 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.

  PMID: 27051417 BACKGROUND

• 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.

  PMID: 28811963 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Michale Soulen, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2020
• First Posted: June 12, 2020
• Study Start: August 26, 2020
• Primary Completion: January 31, 2024
• Study Completion: January 31, 2024
• Last Updated: April 26, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)