89Zr-girentuximab PET Imaging for Cancer

Recruiting in Palo Alto (17 mi)

+4 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Telix International Pty Ltd

Disqualifiers: Pregnancy, Breastfeeding, Renal insufficiency, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

A prospective, open-label, phase 2 study to explore CAIX expression through 89Zirconium-labelled girentuximab deferoxamine (89Zr-girentuximab) PET/CT imaging in patients with solid tumors.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have had any antineoplastic treatment (cancer treatment) within 14 days before starting the trial.

What data supports the effectiveness of the drug 89Zr-girentuximab for cancer?

The drug 89Zr-girentuximab is shown to be a valuable tool in diagnosing clear cell renal cell carcinoma (ccRCC), as it helps confirm or exclude the presence of this cancer type and guides clinical decisions, such as surgery or active surveillance, in cases where the diagnosis is unclear. ^{1 2 3 4 5}

Is 89Zr-girentuximab safe for use in humans?

In a phase I study, 89Zr-girentuximab was evaluated for safety in patients with suspected renal cell carcinoma, indicating it has been tested for safety in humans. ^{1 3 4 6 7}

How is 89Zr-girentuximab PET imaging different from other treatments for cancer?

89Zr-girentuximab PET imaging is unique because it uses a radioactive tracer combined with an antibody that specifically targets a protein found in most clear cell renal cell carcinomas (ccRCC). This allows for precise imaging to confirm or rule out ccRCC, helping doctors make better decisions about surgery or monitoring, and potentially avoiding unnecessary biopsies. ^{1 3 4 8 9}

Research Team

Eligibility Criteria

This trial is for adults with certain solid tumors who can follow the study plan. They must have a measurable tumor, agree to use double-barrier contraception, and not be in other studies from consent until the last visit. Pregnant or breastfeeding women, those allergic to girentuximab or its components, people recently treated with similar drugs or radionuclides, and patients with severe kidney issues are excluded.

Inclusion Criteria

I understand the study and can follow all its requirements.

I agree to use two forms of birth control for at least 42 days after treatment.

Written and voluntarily given Informed Consent

Exclusion Criteria

Exposure to murine or chimeric antibodies within the last 5 years

Clinically significant abnormalities detected during screening laboratory tests or physical exam that would adversely affect the participant's ability to participate in the study

I haven't had any radionuclide treatments recently.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Diagnostic Administration

Single diagnostic administration of 89Zr-girentuximab followed by a diagnostic scan

5 days ± 2 days

1 visit (in-person)

Imaging and Safety Evaluation

PET/CT imaging to assess 89Zr-girentuximab uptake and evaluation of safety parameters

7 days

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

Treatment Details

Interventions

• Girentuximab (Monoclonal Antibodies)

Trial Overview The study tests if a PET/CT scan using a tracer called 89Zr-girentuximab can show CAIX expression in various solid tumors. It's an open-label phase 2 trial where participants receive this radioactive diagnostic agent to help visualize their cancer more clearly on scans.

Who Is Running the Clinical Trial?

Telix International Pty Ltd

Lead Sponsor

Trials

19

Recruited

1,300+

Telix Pharmaceuticals (Innovations) Pty Limited

Lead 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 introduces a new imaging technique using (124)I-labeled chimeric monoclonal antibody G250, which helps accurately locate and confirm the extent of clear cell renal cell carcinoma (ccRCC) before and during surgery.

This innovative approach has the potential to enhance surgical outcomes by guiding complete tumor removal and improving diagnostic accuracy, operative planning, and monitoring for disease recurrence in ccRCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multimodal imaging and detection strategy with 124 I-labeled chimeric monoclonal antibody cG250 for accurate localization and confirmation of extent of disease during laparoscopic and open surgical resection of clear cell renal cell carcinoma. Povoski, SP., Hall, NC., Murrey, DA., et al.[2021]

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]

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 pilot study of 10 patients with therapy-refractory interstitial pneumonitis treated with rituximab, PET/CT imaging using [89Zr]Zr-rituximab showed increased lung activity in four patients, suggesting potential for this imaging technique to predict treatment response.

One patient experienced a severe allergic reaction to the initial rituximab infusion, but subsequent imaging with [89Zr]Zr-rituximab was well-tolerated, indicating that this imaging method may be safe even after adverse reactions to the full drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[89Zr]Zr-rituximab PET/CT activity in patients with therapy refractory interstitial pneumonitis: a feasibility study. Adams, H., van de Garde, EM., van Moorsel, CH., et al.[2020]

Girentuximab (cG250) effectively targets carbonic anhydrase IX (CAIX) on renal cancer cells, and its labeling with 177Lu for radioimmunotherapy has been optimized to maintain immunoreactivity, crucial for effective treatment.

In vivo studies showed that tumor uptake of the radiolabeled cG250 was less than 10% ID/g, attributed to factors like necrotic areas, heterogeneous CAIX expression, and low vascularity, which may limit the effectiveness of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Radiolabeled Girentuximab In Vitro and In Vivo. Basaco, T., Pektor, S., Bermudez, JM., et al.[2023]

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]

89Zr-immuno-PET imaging can help identify cancer patients who are likely to respond to targeted therapies, potentially improving treatment outcomes by ensuring that only those who will benefit receive these therapies.

The use of 89Zr-immuno-PET in conjunction with antibody-drug conjugates (ADCs) allows for better prediction of drug delivery to tumors and helps optimize dosing regimens, enhancing the efficacy and safety of cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of Immuno-PET in Antibody-Drug Conjugate Development. Carmon, KS., Azhdarinia, A.[2019]

89Zirconium-immuno-PET (89Zr-immuno-PET) can effectively assess tumor uptake of trastuzumab, showing that uptake increases with target concentration before plateauing, which is influenced by the total administered dose of the antibody.

The study highlights the importance of defining clinical target positivity cut-offs, as false-positive results can occur depending on the threshold used for immunohistochemistry scores, particularly when using a standard imaging dose of 50 mg of 89Zr-trastuzumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential and pitfalls of 89Zr-immuno-PET to assess target status: 89Zr-trastuzumab as an example. Huisman, MC., Menke-van der Houven van Oordt, CW., Zijlstra, JM., et al.[2021]

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

Multimodal imaging and detection strategy with 124 I-labeled chimeric monoclonal antibody cG250 for accurate localization and confirmation of extent of disease during laparoscopic and open surgical resection of clear cell renal cell carcinoma. [2021]

3. 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]

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

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

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

[89Zr]Zr-rituximab PET/CT activity in patients with therapy refractory interstitial pneumonitis: a feasibility study. [2020]

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

Evaluation of Radiolabeled Girentuximab In Vitro and In Vivo. [2023]

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

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

8. England pubmed.ncbi.nlm.nih.gov

Application of Immuno-PET in Antibody-Drug Conjugate Development. [2019]

9. Germany pubmed.ncbi.nlm.nih.gov

Potential and pitfalls of 89Zr-immuno-PET to assess target status: 89Zr-trastuzumab as an example. [2021]