Clinical Trials /

89Zr-DFO-Atezolizumab ImmunoPET/CT in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma

NCT04006522

Description:

This is an exploratory clinical trial to assess the potential of 89Zr-DFO-Atezolizumab Positron Emission Tomography/Computed Tomography (PET/CT) scans in patients with locally advanced or metastatic renal cell carcinoma (RCC). This open label, nontherapeutic trial will test the correlation of 89Zr-DFO-Atezolizumab immunoPET/CT with programmed death-ligand 1 (PD-L1) expression and the response to immune checkpoint inhibitor therapy in patients with RCC. There will be two cohorts, one made up of patients with localized RCC who will undergo 89Zr-DFO-Atezolizumab PET/CT prior to nephrectomy and a second cohort of patients with metastatic RCC who will undergo 89Zr-DFO-Atezolizumab PET/CT prior to treatment with an immune checkpoint inhibitor.

Related Conditions:
  • Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 89Zr-DFO-Atezolizumab ImmunoPET/CT in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma
  • Official Title: An Exploratory Study of 89Zr-DFO-Atezolizumab ImmunoPET/CT in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: STU-2019-0714
  • NCT ID: NCT04006522

Conditions

  • Renal Cell Carcinoma

Interventions

DrugSynonymsArms
89Zr-DFO-AtezolizumabCohort 1

Purpose

This is an exploratory clinical trial to assess the potential of 89Zr-DFO-Atezolizumab Positron Emission Tomography/Computed Tomography (PET/CT) scans in patients with locally advanced or metastatic renal cell carcinoma (RCC). This open label, nontherapeutic trial will test the correlation of 89Zr-DFO-Atezolizumab immunoPET/CT with programmed death-ligand 1 (PD-L1) expression and the response to immune checkpoint inhibitor therapy in patients with RCC. There will be two cohorts, one made up of patients with localized RCC who will undergo 89Zr-DFO-Atezolizumab PET/CT prior to nephrectomy and a second cohort of patients with metastatic RCC who will undergo 89Zr-DFO-Atezolizumab PET/CT prior to treatment with an immune checkpoint inhibitor.

Detailed Description

      PD-L1 expression in tissue of a variety of tumor types has both prognostic and predictive
      significance for patients treated with immune checkpoint inhibitors. A number of efforts are
      underway to better identify patients who will benefit from immune checkpoint inhibition.
      Among these efforts are the use of radiolabeled antibodies against PD-L1. While under
      investigation in a number of tumor types, to our knowledge this is the first such effort in
      renal carcinoma, despite the clear evidence of clinical efficacy of immune checkpoint
      inhibitors in kidney cancer. Our primary aim with this study is to explore
      89Zr-DFO-Atezolizumab as a positron emission tomography (PET) tracer in patients with RCC.

      The study involves 40 patients distributed across two different groups. The first group is
      made up of patients with high risk localized disease that will be having surgery.
      89Zr-DFO-Atezolizumab PET/CT prior to surgery will be correlated with PD-L1. The second group
      is made up of patients with unresectable or metastatic RCC that will receive an
      anti-programmed death 1 (PD1)/programmed death-ligand 1 antibody (alone or in combination).
      89Zr-DFO-Atezolizumab PET uptake at site of diseases will be evaluated within and across
      patients and correlated with treatment responsiveness in exploratory analyses. Each cohort
      will be comprised of 15-25 patients. Patients will be followed for signs of recurrence or
      progression of their cancer and repeat 89Zr-DFO-Atezolizumab PET scans will be offered at
      that time. Biopsy after subsequent PET/CT will be strongly encouraged.

      Subjects will have data collected during the course of routine clinical care including
      response to immune checkpoint inhibitor therapy, and toxicities developed during immune
      checkpoint inhibitor therapy.

      Co-primary endpoints will be an exploratory analysis correlating 89Zr-DFO-Atezolizumab uptake
      with PD-L1 immunohistochemical (IHC) analyses in locally advanced kidney cancer (cohort 1)
      and an investigation of whether 89Zr-DFO-Atezolizumab uptake across metastatic sites of
      kidney cancer correlates with known radiographically evident metastatic sites of disease,
      PD-L1 expression, and response to anti-PD1/PD-L1 immunotherapy treatment.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1ExperimentalPatients with Localized RCC prior to nephrectomy.
  • 89Zr-DFO-Atezolizumab
Cohort 2ExperimentalPatients with Unresectable/Metastatic RCC prior to treatment with an immune checkpoint inhibitor.
  • 89Zr-DFO-Atezolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with suspected renal cell carcinoma with planned surgery or patients with
             metastatic RCC and a tissue diagnosis.

          -  Ability to understand and the willingness to sign a written informed consent.

          -  Patient must be able to lie still for a 30 to 60 minute PET/CT scan.

          -  One of the following:

               1. Patients with locally advanced RCC planned for nephrectomy determined to be a
                  high risk of recurrence, defined by presence of at least clinical T2 or
                  thioredoxin 1 (TxN1), OR patients with metastatic RCC for whom treatment with
                  metastasectomy is planned by the treating physician.

               2. Patients with metastatic RCC for whom checkpoint inhibitor therapy including an
                  anti-PD1/PD-L1 agent is planned.

          -  Women of child-bearing potential must agree to undergo and have documented a negative
             pregnancy test on the day of 89Zr-DFO-Atezolizumab administration.

        Exclusion Criteria:

          -  History of severe allergic, anaphylactic, or other hypersensitivity reactions to
             atezolizumab or any other chimeric or humanized antibodies.

          -  Concurrent use of an immune checkpoint inhibitor.

          -  Uncontrolled severe and irreversible intercurrent illness or psychiatric
             illness/social situations that would limit compliance with study requirements.

          -  Subjects must not be pregnant or nursing due to the potential for congenital
             abnormalities and the potential of this regimen to harm nursing infants.

          -  Significant autoimmune disease requiring treatment with either prednisone (or steroid
             equivalent) at a dose > 10 mg/day or other immunosuppressive agents. (Replacement
             steroid therapy is acceptable).

          -  Any patient for whom immune checkpoint inhibitor therapy would be contraindicated for
             other reasons.

          -  Subjects unable to provide informed consent.

          -  Subjects who are claustrophobic or have other contraindications to PET/CT.

          -  Subjects must not weigh more than the maximum weight limit for the table for the
             PET/CT scanner where the study is being performed. (>200 kg or 440 lbs).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Correlation between 89Zr-DFO-Atezolizumab and PD-L1
Time Frame:Up to 5 years
Safety Issue:
Description:Correlation between 89Zr-DFO-Atezolizumab PET/CT and PD-L1 expression at the time of nephrectomy in patients with localized kidney cancer.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Orhan Kemal Oz

Trial Keywords

  • renal cell carcinoma
  • atezolizumab
  • PET/CT

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