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

NCT ID: NCT04429321

Last Updated: 2024-04-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

1 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-08-26

Study Completion Date

2024-01-31

Brief Summary

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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

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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.

Conditions

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Renal Cell Carcinoma Renal Cell Carcinoma Stage IV

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Ipilimumab +Nivolumab with Embolization

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.

Group Type EXPERIMENTAL

Nivolumab

Intervention Type DRUG

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

Ipilimumab

Intervention Type DRUG

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

bland embolization

Intervention Type DEVICE

Lipiodol:ethanol embolization of their primary or target tumor

Interventions

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Nivolumab

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

Intervention Type DRUG

Ipilimumab

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

Intervention Type DRUG

bland embolization

Lipiodol:ethanol embolization of their primary or target tumor

Intervention Type DEVICE

Other Intervention Names

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Opdivo Yervoy trans-arterial embolization

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Abramson Cancer Center at Penn Medicine

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michale Soulen, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

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Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 29562145 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10683065 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 3293153 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19007768 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16953240 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27051417 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28811963 (View on PubMed)

Other Identifiers

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843082

Identifier Type: OTHER

Identifier Source: secondary_id

UPCC 06820

Identifier Type: -

Identifier Source: org_study_id

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