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

Primary Purpose

Renal Cell Carcinoma, Renal Cell Carcinoma Stage IV

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Nivolumab

Ipilimumab

bland embolization

About this trial

This is an interventional treatment trial for Renal Cell Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

Hospital of the University of PennsylvaniaRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ipilimumab +Nivolumab with Embolization

Arm 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.

Outcomes

Primary Outcome Measures

Rate of serious adverse events

SAE rate following embolization in patients

Secondary Outcome Measures

Objective response rate

Objective response rate by RECIST 1.1

Characterization of immune cells

Characterization of tumor-infiltrating leukocytes in primary and metastatic lesions before and after embolotherapy

PD-L1

Percentage of PD-L1 stain positivity in the primary tumor biopsy of participants

Full Information

NCT ID

NCT04429321

First Posted

June 9, 2020

Last Updated

October 6, 2023

Sponsor

Abramson Cancer Center at Penn Medicine

1. Study Identification

Unique Protocol Identification Number

NCT04429321

Brief Title

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

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

August 26, 2020 (Actual)

Primary Completion Date

November 2023 (Anticipated)

Study Completion Date

December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Abramson Cancer Center at Penn Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Yes

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Renal Cell Carcinoma, Renal Cell Carcinoma Stage IV

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

22 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Ipilimumab +Nivolumab with Embolization

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Nivolumab

Other Intervention Name(s)

Opdivo

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Ipilimumab

Other Intervention Name(s)

Yervoy

Intervention Description

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

Intervention Type

Device

Intervention Name(s)

bland embolization

Other Intervention Name(s)

trans-arterial embolization

Intervention Description

Lipiodol:ethanol embolization of their primary or target tumor

Primary Outcome Measure Information:

Title

Rate of serious adverse events

Description

SAE rate following embolization in patients

Time Frame

Serious adverse events will be recorded from time of informed to consent to 100 days after the end of study intervention

Secondary Outcome Measure Information:

Title

Objective response rate

Description

Objective response rate by RECIST 1.1

Time Frame

Measured from baseline to 6 months post initiation

Title

Characterization of immune cells

Description

Characterization of tumor-infiltrating leukocytes in primary and metastatic lesions before and after embolotherapy

Time Frame

From baseline to 12 weeks post initiation of therapy

Title

PD-L1

Description

Percentage of PD-L1 stain positivity in the primary tumor biopsy of participants

Time Frame

From baseline to 12 weeks post initiation of therapy

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Michael Soulen, MD

Phone

855-216-0098

michael.soulen@pennmedicine.upenn.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michale Soulen, MD

Organizational Affiliation

University of Pennsylvania

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hospital of the University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Michael C Soulen, MD, FSIR

Phone

855-216-0098

michael.soulen@uphs.upenn.edu

First Name & Middle Initial & Last Name & Degree

Michael C Soulen, MD, FSIR

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

29562145

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.

Results Reference

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PubMed Identifier

10683065

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.

Results Reference

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PubMed Identifier

3293153

Citation

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

Results Reference

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PubMed Identifier

19007768

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.

Results Reference

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PubMed Identifier

16953240

Citation

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.

Results Reference

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PubMed Identifier

27051417

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.

Results Reference

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PubMed Identifier

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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.

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

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