New Imaging Technique for Kidney Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Jonsson Comprehensive Cancer Center

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

Disqualifiers: Residual disease, Non-renal malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 10

Duration: 1 week

91 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new imaging method, using a special radioactive tracer called Zirconium Zr 89 Girentuximab, can better detect kidney cancer that has returned after surgery. The current standard method might miss small cancer spots, so the trial tests whether the new method is more effective. People who have had kidney cancer surgery and are at high risk of recurrence might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to potentially groundbreaking advancements in cancer detection.

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 prior data suggests that this imaging technique is safe for detecting recurrent kidney cancer?

Research has shown that the 89Zr-DFO-girentuximab PET/CT scan is generally safe for people. Several studies have found that patients tolerate it well. For instance, one study highlighted that this imaging method is safe. Another study supported this by noting that patients with suspected kidney cancer tolerate it well. Overall, the evidence suggests that using 89Zr-DFO-girentuximab for PET/CT scans is safe and does not cause significant side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the new imaging technique for kidney cancer because it uses Zirconium Zr 89 Girentuximab, a novel radiolabeled antibody. Unlike traditional imaging methods, this technique targets a specific protein on kidney cancer cells, potentially offering more precise tumor visualization. This could lead to better diagnosis, monitoring, and treatment decisions, ultimately improving patient outcomes.

What evidence suggests that this imaging technique is effective for detecting recurrent kidney cancer?

Research has shown that 89Zr-DFO-girentuximab PET/CT imaging, which participants in this trial will undergo, accurately identifies clear cell renal cell carcinoma, a type of kidney cancer. This method uses a special antibody that attaches to a protein on cancer cells, making them visible on PET scans. Studies indicate it is safe and detects cancer more precisely than some older methods. This imaging technique may better find small or hidden tumors compared to standard contrast-enhanced CT scans. Overall, evidence suggests this method could help detect cancer recurrences earlier. ^{1 2 3 6 7}

Who Is on the Research Team?

Brian Shuch, MD

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Zirconium Zr 89 Girentuximab

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.

How Is the Trial Designed?

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.

Zirconium Zr 89 Girentuximab is already approved in United States, European Union for the following indications:

Approved in United States as TLX250-CDx for:

• Detection and characterization of clear-cell renal cell carcinoma

Approved in European Union as TLX250-CDx for:

• Detection and characterization of clear-cell renal cell carcinoma

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

Telix Pharmaceuticals (Innovations) Pty Limited

Industry Sponsor

Trials

23

Recruited

2,400+

Published Research Related to This Trial

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11322881/

Evaluation of PET/CT imaging with [89Zr]Zr-DFO-girentuximab This study demonstrates that [ 89 Zr]Zr-DFO-girentuximab administered to Japanese patients with suspected RCC has a favorable safety profile and is well ...

2. jnm.snmjournals.org jnm.snmjournals.org/content/64/supplement_1/p257

Zirconium-labelled Girentuximab (89Zr-TLX250-CDx) PET/CT ... 89Zr-DFO-girentuximab PET/CT imaging can accurately detect clear cell renal cell carcinoma primary and secondary lesions in patients with renal masses at conven ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06750419?term=telix&page=1&viewType=Table&rank=4

NCT06750419 | 89Zr-TLX250 for PET/CT Imaging of ccRCC The study is designed to evaluate the safety, tolerability, sensitivity and specificity of 89Zr-TLX250 Positron Emission Tomography/Computed Tomography (PET/CT) ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39270701/

[89Zr]Zr-girentuximab for PET-CT imaging of clear-cell ... We aimed to evaluate [89Zr]Zr-girentuximab PET-CT imaging for detection and characterisation of clear-cell renal cell carcinoma. Methods: ZIRCON ...

5. urotoday.com urotoday.com/actionable-clinical-data/zircon-trial.html

ZIRCON Phase III Study: [89Zr]Zr-girentuximab for PET/CT ... ZIRCON Phase III Study: [89Zr]Zr-girentuximab for PET/CT Imaging of ccRCC · Functional Renal Imaging and Advances in Kidney Cancer Detection - Shankar Siva.

6. urotoday.com urotoday.com/conference-highlights/asco-gu-2023/asco-gu-2023-kidney-cancer/142594-asco-gu-2023-zircon-results-from-phase-3-study-of-89zr-dfo-girentuximab-for-pet-ct-imaging-of-clear-cell-renal-cell-carcinoma.html

ZIRCON: Results from Phase 3 Study of 89Zr-DFO ... The favorable safety and tolerability profile of 89Zr-DFO-girentuximab was confirmed. Dr. Shuch's take home points are as follows: 89Zr-DFO ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02883153

Zirconium-89-girentuximab PET/CT Imaging in Renal Cell ... The aim of the present study is to show the impact of the Zr-89-girentuximab PET/CT on the clinical management of ccRCC patients. Detailed Description. More ...