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

Primary Purpose

Renal Cell Carcinoma

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

89Zr-DFO-Atezolizumab

Positron Emission Tomography/Computed Tomography

About this trial

This is an interventional diagnostic trial for Renal Cell Carcinoma focused on measuring renal cell carcinoma, atezolizumab, PET/CT

Eligibility Criteria

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

Inclusion Criteria:

Patients with suspected renal cell carcinoma with planned surgery or patients with metastatic RCC and a tissue diagnosis. (In standard clinical practice, biopsy is not routinely performed in patients who will be having surgery).
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 surgery 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 immuno-oncology (IO) therapy 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. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy; or
- Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).

Exclusion Criteria:

History of severe allergic, anaphylactic, or other hypersensitivity reactions to atezolizumab or any other chimeric or humanized antibodies.
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 ICI therapy would be contraindicated for other reasons. Patients with adverse reactions to ICI therapy may undergo second 89Zr-DFO-Atezolizumab injection and PET/CT at the discretion of the treating physician considering that the dose of antibody represents 1% of a single therapeutic dose and therefore unlikely to cause adverse events.
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).

Sites / Locations

UT Southwestern Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Cohort 1

Cohort 2

Arm Description

Patients with Localized RCC prior to nephrectomy.

Patients with Unresectable/Metastatic RCC prior to treatment with an immune checkpoint inhibitor.

Outcomes

Primary Outcome Measures

Correlation between 89Zr-DFO-Atezolizumab and PD-L1

Correlation between 89Zr-DFO-Atezolizumab PET/CT and PD-L1 expression at the time of nephrectomy in patients with localized kidney cancer.

Correlation between 89Zr-DFO-Atezolizumab and anti-PD1/PD-L1 therapy

Correlation between 89Zr-DFO-Atezolizumab PET/CT and response to anti-PD1/PD-L1 therapy.

Secondary Outcome Measures

Full Information

NCT ID

NCT04006522

First Posted

July 1, 2019

Last Updated

June 1, 2023

Sponsor

James Brugarolas

1. Study Identification

Unique Protocol Identification Number

NCT04006522

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Recruiting

Study Start Date

October 2, 2019 (Actual)

Primary Completion Date

July 15, 2024 (Anticipated)

Study Completion Date

July 15, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

James Brugarolas

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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. 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. This is an exploratory analysis correlating 89Zr-DFO-Atezolizumab uptake with PD-L1 immunohistochemical (IHC) analyses in locally advanced kidney cancer (cohort 1) and will evaluate 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.

6. Conditions and Keywords

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

Renal Cell Carcinoma

Keywords

renal cell carcinoma, atezolizumab, PET/CT

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1

Arm Type

Experimental

Arm Description

Patients with Localized RCC prior to nephrectomy.

Arm Title

Cohort 2

Arm Type

Experimental

Arm Description

Patients with Unresectable/Metastatic RCC prior to treatment with an immune checkpoint inhibitor.

Intervention Type

Drug

Intervention Name(s)

89Zr-DFO-Atezolizumab

Intervention Description

89Zr-DFO-Atezolizumab infusion

Intervention Type

Procedure

Intervention Name(s)

Positron Emission Tomography/Computed Tomography

Other Intervention Name(s)

PET/CT

Intervention Description

PET/CT scan 7 days (± 1 day) after infusion of 89Zr-DFO-Atezolizumab.

Primary Outcome Measure Information:

Title

Correlation between 89Zr-DFO-Atezolizumab and PD-L1

Description

Correlation between 89Zr-DFO-Atezolizumab PET/CT and PD-L1 expression at the time of nephrectomy in patients with localized kidney cancer.

Time Frame

Up to 5 years

Title

Correlation between 89Zr-DFO-Atezolizumab and anti-PD1/PD-L1 therapy

Description

Correlation between 89Zr-DFO-Atezolizumab PET/CT and response to anti-PD1/PD-L1 therapy.

Time Frame

Up to 5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients with suspected renal cell carcinoma with planned surgery or patients with metastatic RCC and a tissue diagnosis. (In standard clinical practice, biopsy is not routinely performed in patients who will be having surgery). 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: Patients with locally advanced RCC planned for surgery determined to be a high risk of recurrence, defined by presence of at least clinical T2 or TxN1, OR patients with metastatic RCC for whom treatment with cytoreductive nephrectomy and/or metastasectomy is planned by the treating physician. Patients with metastatic RCC for whom immuno-oncology (IO) therapy 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. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: Has not undergone a hysterectomy or bilateral oophorectomy; or Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months). Exclusion Criteria: History of severe allergic, anaphylactic, or other hypersensitivity reactions to atezolizumab or any other chimeric or humanized antibodies. 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 ICI therapy would be contraindicated for other reasons. Patients with adverse reactions to ICI therapy may undergo second 89Zr-DFO-Atezolizumab injection and PET/CT at the discretion of the treating physician considering that the dose of antibody represents 1% of a single therapeutic dose and therefore unlikely to cause adverse events. 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).

Central Contact Person:

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

Kelli Key, PhD

Phone

214-648-8152

Kelli.Key@UTSouthwestern.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

James Brugarolas, MD, PhD

Organizational Affiliation

UT Southwestern Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

UT Southwestern Medical Center

City

Dallas

State/Province

Texas

ZIP/Postal Code

75390

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Kelli Key, PhD

Phone

214-648-8152

Kelli.Key@UTSouthwestern.edu

First Name & Middle Initial & Last Name & Degree

James Brugarolas, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

36074149

Citation

Mulgaonkar A, Elias R, Woolford L, Guan B, Nham K, Kapur P, Christie A, Tcheuyap VT, Singla N, Bowman IA, Stevens C, Hao G, Brugarolas J, Sun X. ImmunoPET Imaging with 89Zr-Labeled Atezolizumab Enables In Vivo Evaluation of PD-L1 in Tumorgraft Models of Renal Cell Carcinoma. Clin Cancer Res. 2022 Nov 14;28(22):4907-4916. doi: 10.1158/1078-0432.CCR-22-1547.

Results Reference

derived

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

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