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

April 25, 2024 updated by: Abramson Cancer Center at Penn Medicine

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

1

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Hospital of the University of Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: Nivolumab
Nivolumab 3 mg/kg IV every four weeks, first in combination with capecitabine then alone
Other Names:
  • Opdivo
Drug: Ipilimumab
ipilimumab 1/mg/kg IV every 3 weeks x 4 cycles, in combination with Nivolumab
Other Names:
  • Yervoy
Device: bland embolization
Lipiodol:ethanol embolization of their primary or target tumor
Other Names:
  • trans-arterial embolization

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of serious adverse events
Time Frame: Serious adverse events will be recorded from time of informed to consent to 100 days after the end of study intervention
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate
Time Frame: Measured from baseline to 6 months post initiation
Objective response rate by RECIST 1.1
Measured from baseline to 6 months post initiation
Characterization of immune cells
Time Frame: From baseline to 12 weeks post initiation of therapy
Characterization of tumor-infiltrating leukocytes in primary and metastatic lesions before and after embolotherapy
From baseline to 12 weeks post initiation of therapy
PD-L1
Time Frame: From baseline to 12 weeks post initiation of therapy
Percentage of PD-L1 stain positivity in the primary tumor biopsy of participants
From baseline to 12 weeks post initiation of therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Abramson Cancer Center at Penn Medicine

Investigators

  • Principal Investigator: Michale Soulen, MD, University of Pennsylvania

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 26, 2020

Primary Completion (Actual)

January 31, 2024

Study Completion (Actual)

January 31, 2024

Study Registration Dates

First Submitted

June 9, 2020

First Submitted That Met QC Criteria

June 9, 2020

First Posted (Actual)

June 12, 2020

Study Record Updates

Last Update Posted (Actual)

April 26, 2024

Last Update Submitted That Met QC Criteria

April 25, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UPCC 06820
  • 843082 (Other Identifier: University of Pennsylvania IRB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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