Clinical Trials /

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

NCT04429321

Description:

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.

Related Conditions:
  • Renal Cell Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: 843082
  • NCT ID: NCT04429321

Conditions

  • Renal Cell Carcinoma
  • Renal Cell Carcinoma Stage IV

Interventions

DrugSynonymsArms
NivolumabOpdivoIpilimumab +Nivolumab with Embolization
IpilimumabYervoyIpilimumab +Nivolumab with Embolization

Purpose

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 will undergo two
      cycles of combination immune checkpoint inhibition (ICI) therapy, embolization of the primary
      tumor, then resume ICI therapy. Study ends with safety and efficacy assessment at 6 months.
      Correlative blood and tissue specimens will be obtained.
    

Trial Arms

NameTypeDescriptionInterventions
Ipilimumab +Nivolumab with EmbolizationExperimentalPatients receive ICI therapy with Nivolumab 3 mg/kg + ipilimumab 1/mg/kg IV every 3 weeks x 4 cycles, followed by nivolumab 3 mg/kg 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 Lipiodol:ethanol embolization of their primary tumor and continue systemic therapy subsequently.
  • Nivolumab
  • Ipilimumab

Eligibility Criteria

        Inclusion Criteria:

          1. Metastatic renal cell carcinoma with unresected primary tumor

          2. No prior immune checkpoint therapy

          3. Primary tumor amenable to percutaneous embolization

          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. 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. Known history of testing positive for human immunodeficiency virus (HIV) or known
             acquired immunodeficiency syndrome (AIDS)

          9. Contrast allergy not mitigated by usual prophylaxis
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:SAE rate following embolization in patients

Secondary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Pennsylvania

Last Updated

June 9, 2020