89Zr-girentuximab PET Imaging for Cancer

(STARBURST Trial)

No longer recruiting at 10 trial locations

Overseen By Kavita Vadali

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Telix Pharmaceuticals (Innovations) Pty Ltd

Disqualifiers: Pregnancy, Breastfeeding, Renal insufficiency, 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

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to detect the expression of a specific protein, CAIX, in certain solid tumors using a special PET scan with the compound 89Zr-girentuximab (a monoclonal antibody). The goal is to enhance how doctors view and understand tumors in conditions like cervical, lung, and ovarian cancers, among others. The trial seeks participants diagnosed with one of these cancers who have a measurable tumor outside the brain. Those meeting these criteria may find this trial suitable. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that 89Zr-girentuximab is likely to be safe for humans?

Research has shown that 89Zr-girentuximab is generally safe and well-tolerated for imaging use. In one study, patients who received 89Zr-girentuximab experienced no major side effects. The study examined the treatment's movement through the body and its safety. Results indicated that the treatment is safe at the administered doses. This suggests that 89Zr-girentuximab can be safely used in imaging techniques for certain cancers. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about 89Zr-girentuximab because it offers a unique approach to cancer imaging. Unlike traditional imaging methods that might not effectively target specific cancer cells, 89Zr-girentuximab is a radiolabeled antibody that specifically binds to carbonic anhydrase IX (CAIX), a protein often overexpressed in certain cancers. This targeted binding allows for more precise imaging of cancerous tissues, potentially leading to earlier and more accurate detection. This innovative mechanism could enhance the management and treatment planning for patients by providing clearer insights into the presence and extent of the disease.

What evidence suggests that 89Zr-girentuximab PET imaging is effective for cancer?

Research has shown that 89Zr-girentuximab, which participants in this trial will receive, effectively detects clear cell renal cell carcinoma (ccRCC) using PET/CT scans. Studies report a mean sensitivity of 86%, correctly identifying the disease 86% of the time, and a mean specificity of 87%, correctly identifying those without the disease 87% of the time. These results indicate that the imaging method accurately diagnoses ccRCC. Patients tolerate it well, and this accuracy can help guide treatment decisions. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Girentuximab

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.

How Is the Trial Designed?

Group I: 89Zr-TLX250 Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Telix Pharmaceuticals (Innovations) Pty Ltd

Lead Sponsor

Trials

3

Recruited

870+

Telix International Pty Ltd

Lead Sponsor

Trials

19

Recruited

1,300+

Telix Pharmaceuticals (Innovations) Pty Limited

Lead Sponsor

Trials

23

Recruited

2,400+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. asco.org asco.org/abstracts-presentations/ABSTRACT396010

Results from phase 3 study of 89Zr-DFO-girentuximab for ... Conclusions: This study confirms that TLX250-CDx PET/CT is well tolerated and can accurately and noninvasively identify ccRCC, with promising utility for ...

2. telixpharma.com telixpharma.com/news-views/highly-accurate-telixs-phase-iii-zircon-trial-for-kidney-cancer-imaging-published-in-the-lancet-oncology/

'Highly Accurate': Telix's Phase III ZIRCON Trial for Kidney ... Zr-girentuximab PET/CT imaging accurately detected ccRCC in patients with cT1 IRM (≤7cm), demonstrating a mean sensitivity of 86%, specificity ...

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

[89Zr]Zr-girentuximab for PET/CT Imaging of ccRCC Novel imaging approaches are urgently needed to refine diagnostic accuracy and guide patient management.

4. cancernetwork.com cancernetwork.com/view/developer-submits-bla-for-tlx250-cdx-kidney-cancer-imaging-in-ccrcc

Developer Submits BLA for TLX250-CDx Kidney Cancer ... The imaging product demonstrated a mean sensitivity of 85.5% (95% CI, 81.5%-89.6%) and a mean specificity of 87.0% (95% CI, 81.0%-93.1%). Per ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.4554

89Zr-DFO-girentuximab for PET/CT imaging of clear cell ... Of 284 evaluable patients, the average across all 3 readers for sensitivity and specificity was 86% [80%, 90%] and 87% [79%, 92%] resp. for ...

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

89Zr-TLX250 for PET/CT Imaging of ccRCC - ZIRCON-CP ... 89Zr-TLX250, is a chimeric monoclonal antibody (INN name: girentuximab) with specificity for the CAIX (carbonic anhydrase 9) antigen, radiolabelled with the ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39520979/

[89Zr]Zr-girentuximab PET-CT imaging to diagnose ... This imaging technique could be a promising tool that could revolutionize the management of small renal masses (SRMs) and ccRCC.

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33651116/

Phase I study to assess safety, biodistribution and radiation ... This study demonstrates that 89 Zr-girentuximab is safe and well tolerated for the administered activities and mass doses and allows quantitative assessment.

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

Zirconium-labelled Girentuximab (89Zr-TLX250-CDx) PET/CT ... Radiolabeling girentuximab with Zirconium (89Zr-DFO‑girentuximab, or TLX250-CDx) can be used for ccRCC detection by PET/CT imaging to differentiate ccRCC from ...

10. europeanurology.com europeanurology.com/article/S0302-2838(18)30332-4/fulltext

Positron Emission Tomography/Computed ... This clinical study explores the value of 89Zr-labeled girentuximab positron emission tomography/computed tomography (PET/CT) imaging in ...