New Imaging Technique for Kidney Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Brian Shuch, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Jonsson Comprehensive Cancer Center

Must not be taking: PD-1, PD-L1, others

Disqualifiers: Residual disease, Non-renal malignancy, others

No Placebo Group

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This phase II trial compares the safety and effectiveness of 89Zr-DFO-GmAb positron emission tomography (PET)/computed tomography (CT) compared to contrast-enhanced CT after surgery in detecting clear cell renal cell cancer that has come back (recurrent). For some patients, the risk of recurrence after surgery remains high. Conventional CT methods, such as contrast-enhanced CT, may not detect small volume or micrometastatic disease. PET/CT with radiotracers, such as 89Zr-DFO-GmAb, may improve detection of tumor cells. Girentuximab (GmAb), a monoclonal antibody, is tagged with zirconium-89, a radioactive atom (which is also known as an isotope). The zirconium-89 (89Zr) isotope is attached to girentuximab with desferrioxamine (DFO) and this combined product is called 89Zr-DFO-girentuximab. 89Zr-DFO-girentuximab attaches itself to a protein on the surface of clear cell renal cell tumor cells called CAIX. PET is an established imaging technique that utilizes small amounts of radioactivity attached to very minimal amounts of tracer, in the case of this research, 89Zr-DFO-GmAb. Because some cancers, including clear cell renal cell cancer, take up 89Zr-DFO-GmAb it can be seen with PET. CT utilizes x-rays that traverse body from the outside. CT images provide an exact outline of organs and potential inflammatory tissue where it occurs in patient's body. Using contrast agents with CT scan to enhance the images (contrast-enhanced CT) is standard of care imaging. 89Zr-DFO-GmAb PET/CT may be safe and effective compared to contrast-enhanced CT in detecting recurrent clear cell renal cell cancer after surgery.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you have used certain kidney cancer treatments or experimental drugs recently, you may not be eligible.

What data supports the effectiveness of the drug Zirconium Zr 89 Girentuximab for kidney cancer?

The drug Zirconium Zr 89 Girentuximab has shown effectiveness in helping doctors diagnose clear cell renal cell carcinoma (ccRCC) by accurately identifying cancerous lesions in imaging tests. In one study, it helped change clinical management in 36% of patients and avoided repeat biopsies in 21% of cases, proving useful in guiding treatment decisions. ^{1 2 3 4 5}

Is the new imaging technique for kidney cancer safe for humans?

The imaging technique using Zirconium Zr 89 Girentuximab has been generally well tolerated in studies, with no serious side effects reported in imaging trials. However, a related treatment using a different radioactive label (Lutetium 177) caused some blood-related side effects in a separate study. ^{1 2 3 6 7}

What makes the drug Zirconium Zr 89 Girentuximab unique for kidney cancer?

Zirconium Zr 89 Girentuximab is unique because it uses a special imaging technique to detect kidney cancer by targeting a protein called carbonic anhydrase IX, which is found in most clear cell renal cell carcinomas. This helps doctors make better decisions about treatment by clearly identifying cancerous areas. ^{1 2 3 4 5}

Research Team

Brian Shuch, MD

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Eligibility Criteria

This trial is for individuals who have undergone surgery for clear cell renal cell cancer and are being monitored for possible recurrence of the disease. It's not specified who can't join, but typically, participants need to meet certain health standards.

Inclusion Criteria

Negative serum pregnancy tests in female patients of childbearing potential

My surgery was between 1 to 4 months ago.

My kidney cancer was confirmed by surgery.

Exclusion Criteria

Exposure to experimental diagnostic or therapeutic drug within 14 days from date of planned administration

Known hypersensitivity to girentuximab

I cannot stay still or lie flat during scans.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 89Zr-DFO-GmAb intravenously and undergo PET/CT and contrast-enhanced CT scans

1 week

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Follow-up visits at 8, 16, and 24 months

Treatment Details

Interventions

• Zirconium Zr 89 Girentuximab (Monoclonal Antibodies)

Trial Overview The study is testing a new scan called 89Zr-DFO-GmAb PET/CT against the standard contrast-enhanced CT to see if it's better at finding recurrent kidney cancer after surgery. The investigational scan uses a radioactive tracer that targets tumor cells.

Participant Groups

Group I: Diagnostic (89Zr-DFO-GmAb PET/CT) Experimental Treatment 7 Interventions

Patients receive 89Zr-DFO-GmAb IV over 3 minutes on day 0 then undergo whole body PET/CT and SOC diagnostic contrast-enhanced CT scan on day 7. Patients also blood sample collection on study. In addition, patients may undergo bone scan and CT or MRI of the brain on study as clinically indicated.

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

Dr. Aparna Bhaduri

Jonsson Comprehensive Cancer Center

Chief Medical Officer since 2024

MD

Dr. Michael A. Teitell

Jonsson Comprehensive Cancer Center

Chief Executive Officer since 2024

MD, PhD

Telix Pharmaceuticals (Innovations) Pty Limited

Industry Sponsor

Trials

23

Recruited

2,400+

Findings from Research

The phase I study involving 10 patients showed that [89Zr]Zr-DFO-girentuximab is safe and well tolerated, with no serious treatment-related adverse events reported, indicating its potential for clinical use.

89Zr-girentuximab PET/CT imaging effectively differentiated clear cell renal cell carcinoma (ccRCC) from non-ccRCC lesions in all patients, providing a quantitative assessment of tumor dosimetry, which is crucial for treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study to assess safety, biodistribution and radiation dosimetry for 89Zr-girentuximab in patients with renal cell carcinoma. Merkx, RIJ., Lobeek, D., Konijnenberg, M., et al.[2022]

The study involved 30 patients (16 with primary renal masses and 14 with a history of ccRCC) and demonstrated that 89Zr-labeled girentuximab PET/CT imaging is effective in accurately detecting clear cell renal cell carcinoma (ccRCC), guiding clinical decisions regarding surgery or active surveillance.

In cases of suspected recurrent or metastatic ccRCC, the imaging led to significant changes in clinical management for 36% of patients and helped avoid unnecessary repeat biopsies in 21% of cases, highlighting its utility in complex diagnostic situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positron Emission Tomography/Computed Tomography with 89Zr-girentuximab Can Aid in Diagnostic Dilemmas of Clear Cell Renal Cell Carcinoma Suspicion. Hekman, MCH., Rijpkema, M., Aarntzen, EH., et al.[2019]

In the ARISER trial involving 864 patients with high-risk clear cell renal cell carcinoma (ccRCC), girentuximab did not show a statistically significant improvement in disease-free survival (DFS) or overall survival (OS) compared to placebo, indicating it may not be an effective adjuvant treatment.

Despite the lack of clinical benefit, the study reported a median DFS of 71.4 months for the girentuximab group, suggesting that patients may have longer survival times than expected, which poses challenges for future drug development in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant Weekly Girentuximab Following Nephrectomy for High-Risk Renal Cell Carcinoma: The ARISER Randomized Clinical Trial. Chamie, K., Donin, NM., Klöpfer, P., et al.[2022]

In a study of 42 newly diagnosed patients with metastatic clear cell renal cell carcinoma (mccRCC), the combination of [89Zr]Zr-DFO-girentuximab-PET/CT and CT detected significantly more lesions (91%) compared to CT alone (56%), highlighting the enhanced efficacy of this imaging approach.

Both [89Zr]Zr-DFO-girentuximab-PET/CT and [18F]FDG-PET/CT were more effective than CT alone in identifying bone and soft tissue lesions, suggesting that these advanced imaging techniques can improve lesion detection in patients eligible for watchful waiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lesion detection by [89Zr]Zr-DFO-girentuximab and [18F]FDG-PET/CT in patients with newly diagnosed metastatic renal cell carcinoma. Verhoeff, SR., van Es, SC., Boon, E., et al.[2020]

The study demonstrated that dual-labeled girentuximab can specifically target clear cell renal cell carcinoma (ccRCC) tissue, allowing for effective visualization of tumors during surgery using both radionuclide and fluorescence imaging techniques.

In a trial involving seven human kidney specimens, the maximum uptake of girentuximab in tumor tissue was significantly higher (up to 0.33% of the injected dose per gram) compared to normal kidney tissue (up to 0.04% ID/g), confirming its potential for precise tumor detection in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Dual-Modality Imaging in Renal Cell Carcinoma: An Ex Vivo Kidney Perfusion Study. Hekman, MC., Boerman, OC., de Weijert, M., et al.[2018]

In a phase 2 trial involving 14 patients with metastatic clear cell renal cell carcinoma, lutetium 177-girentuximab radioimmunotherapy led to disease stabilization in 9 patients (64%), indicating its potential efficacy in treating this challenging condition.

While the treatment was generally well tolerated, it caused significant myelotoxicity, leading to prolonged low blood cell counts that prevented some patients from receiving retreatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 Study of Lutetium 177-Labeled Anti-Carbonic Anhydrase IX Monoclonal Antibody Girentuximab in Patients with Advanced Renal Cell Carcinoma. Muselaers, CH., Boers-Sonderen, MJ., van Oostenbrugge, TJ., et al.[2022]

This study demonstrated the safety and feasibility of using a dual-modality imaging approach with the antibody 111In-DOTA-girentuximab-IRDye800CW in 15 patients with clear cell renal cell carcinoma (ccRCC), with no serious adverse events reported.

The dual-modality imaging effectively localized ccRCC tumors during surgery, allowing for better tumor delineation and detection of surgical margins, which is crucial for successful tumor resection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor-targeted Dual-modality Imaging to Improve Intraoperative Visualization of Clear Cell Renal Cell Carcinoma: A First in Man Study. Hekman, MC., Rijpkema, M., Muselaers, CH., et al.[2019]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Phase I study to assess safety, biodistribution and radiation dosimetry for 89Zr-girentuximab in patients with renal cell carcinoma. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Positron Emission Tomography/Computed Tomography with 89Zr-girentuximab Can Aid in Diagnostic Dilemmas of Clear Cell Renal Cell Carcinoma Suspicion. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Adjuvant Weekly Girentuximab Following Nephrectomy for High-Risk Renal Cell Carcinoma: The ARISER Randomized Clinical Trial. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Lesion detection by [89Zr]Zr-DFO-girentuximab and [18F]FDG-PET/CT in patients with newly diagnosed metastatic renal cell carcinoma. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Targeted Dual-Modality Imaging in Renal Cell Carcinoma: An Ex Vivo Kidney Perfusion Study. [2018]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Phase 2 Study of Lutetium 177-Labeled Anti-Carbonic Anhydrase IX Monoclonal Antibody Girentuximab in Patients with Advanced Renal Cell Carcinoma. [2022]

7. Australia pubmed.ncbi.nlm.nih.gov

Tumor-targeted Dual-modality Imaging to Improve Intraoperative Visualization of Clear Cell Renal Cell Carcinoma: A First in Man Study. [2019]