[18F]PT2385 PET/CT Scan for Kidney Cancer

Overseen By Kelli Key, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Orhan Kemal Oz

Must be taking: Belzutifan

Disqualifiers: Pregnancy, Claustrophobia, Weight limit, others

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

Compensation: Varies

Number of Visits: 1

35 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an exploratory study to assess \[18F\]PT2385 Positron Emission Tomography/Computed Tomography (PET/CT) in patients with renal cell carcinoma (RCC). This is an open-label, nontherapeutic trial. The main objective is to correlate hypoxia-inducible factor-2alpha (HIF2α) levels as determined by an investigational \[18F\]PT2385 PET/CT scan with the levels on subsequently obtained tissue by HIF2α immunohistochemistry (IHC). There will be three cohorts. The first pre-surgical cohort will have \[18F\]PT2385 PET/CT prior to nephrectomy. The uptake and retention on Positron Emission Tomography (PET), quantified as standardized uptake value (SUV) max and mean, abbreviated SUV henceforth will be correlated with HIF2α levels by IHC on the primary tumor. The second cohort will comprise patients with metastatic clear cell renal carcinoma (ccRCC). SUV will be correlated with HIF2α levels measured by IHC on a biopsy sample from a metastasis. Both low- and high-avidity sites will be biopsied and tracer uptake correlated with HIF2α IHC. A third cohort will include patients with Von Hippel-Lindau (VHL) syndrome and any of the following disease manifestations - RCC, central nervous system (CNS) hemangioblastoma, and/or pancreatic neuroendocrine tumor(s). Investigational imaging will evaluate HIF2α expression within a tumor type and across different tumor types. A biopsy is encouraged but not mandatory for this cohort.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are planning to start belzutifan as part of Cohort 3, you may need to discuss your current medications with the study team.

Is the [18F]PT2385 PET/CT scan safe for humans?

The safety of [18F]PT2385 PET/CT scans specifically is not directly addressed in the available research, but general safety concerns for similar procedures include potential kidney injury from contrast materials used in CT scans, especially in patients with pre-existing kidney issues. Radiopharmaceutical therapies, which are similar to [18F]PT2385, generally have low impact on kidney function, but precautions are taken to minimize any potential kidney damage. ^{1 2 3 4 5}

How does the [18F]PT2385 PET/CT scan treatment for kidney cancer differ from other treatments?

The [18F]PT2385 PET/CT scan is unique because it uses a specific radiotracer to visualize kidney cancer, potentially offering more precise imaging compared to traditional methods. This approach may help in better assessing the cancer's response to treatment, which is not typically possible with standard imaging techniques. ^{6 7 8 9 10}

Research Team

James Brugarolas, MD, PhD

Principal Investigator

UT Southwestern Medical Center

Eligibility Criteria

This trial is for patients with suspected or confirmed renal cell carcinoma (RCC). It includes those planned for surgery, with metastatic clear cell RCC, or Von Hippel-Lindau syndrome with related tumors. Participants must be able to lie still for PET/CT scans and women of childbearing potential need a negative pregnancy test. Exclusions include severe illnesses, pregnancy, nursing mothers, over the weight limit for PET/CT scanners (>440 pounds), claustrophobia, and unsuitable biopsy sites.

Inclusion Criteria

I can become pregnant and agree to take a pregnancy test before receiving [18F]PT2385.

I can stay still for up to an hour for a scan.

I have kidney cancer with metastasis or VHL syndrome and will undergo a biopsy or surgery for it.

Exclusion Criteria

You are claustrophobic or have other reasons that make it unsafe for you to have a PET/CT scan.

I cannot safely undergo a biopsy due to the location of my cancer.

Uncontrolled severe and irreversible intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging and Evaluation

Participants undergo [18F]PT2385 PET/CT imaging to assess HIF2α expression. Dynamic and whole-body scans are performed at various time points.

1-2 weeks

Multiple visits for imaging

Surgical and Biopsy Procedures

For the pre-surgical cohort, surgery is performed after imaging. For other cohorts, biopsies are conducted to correlate PET/CT results with HIF2α levels.

1-2 weeks

1-2 visits for procedures

Follow-up

Participants are monitored for safety and effectiveness after imaging and procedures. Repeat PET studies may be conducted.

4 weeks

Treatment Details

Interventions

• [18F]PT2385
• Biopsy
• Positron Emission Tomography/Computed Tomography

Trial Overview [18F]PT2385 PET/CT imaging is being tested to see how well it shows levels of HIF2α in kidney cancer compared to tissue tests after surgery or biopsy. The study has three groups: one getting scans before kidney removal; another with metastatic cancer where scan results are matched against biopsies; and a third group with VHL syndrome who may have different types of tumors.

Participant Groups

Group I: Pre-Surgical Experimental Treatment 2 Interventions

Patients with suspected RCC planned for surgery

Group II: Planned belzutifan treatment Experimental Treatment 2 Interventions

Patients with VHL syndrome with RCC, CNS hemangioblastoma, and/or pancreatic neuroendocrine tumor(s) planning to start belzutifan.

Group III: Metastatic or VHL Syndrome Experimental Treatment 3 Interventions

Patients with metastatic ccRCC or VHL syndrome and RCC

Who Is Running the Clinical Trial?

Orhan Kemal Oz

Lead Sponsor

Trials

2

Recruited

80+

Neil M Rofsky, MD, MHA

Lead Sponsor

Trials

2

Recruited

160+

Findings from Research

A study involving 25,184 cancer patients who underwent 46,593 contrast-enhanced CT scans developed a predictive model for contrast-associated acute kidney injury (CA-AKI), identifying key risk factors such as chronic kidney disease and certain medication use.

The model demonstrated that CA-AKI risk significantly increases with higher risk scores, allowing healthcare providers to implement preventive measures for patients identified as high risk, potentially improving patient safety during CT examinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and Validation of a Risk Model for Predicting Contrast-Associated Acute Kidney Injury in Patients With Cancer: Evaluation in Over 46,000 CT Examinations. Gupta, S., Motwani, SS., Seitter, RH., et al.[2023]

Radiopharmaceuticals, like peptide receptor radionuclide therapy (PRRT) using 90Y-DOTATOC, are designed to target cancer cells while minimizing damage to healthy tissues, but they can still pose risks to kidney function due to their clearance through the kidneys.

To reduce nephrotoxicity from PRRT, standard practices include amino acid co-infusion to inhibit kidney reabsorption of the drugs, along with hydration and personalized renal dosimetry, although more research is needed to fully understand the long-term effects on renal health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Impact of Radiopharmaceutical Therapy on Renal Function. Park, EA., Graves, SA., Menda, Y.[2022]

In a study of nearly 30 million inpatient visits, patients with cancer undergoing CT scans with iodinated contrast material (CM) showed a higher risk of acute renal adverse events (AEs) compared to those without cancer, with absolute risk increases ranging from 0.3% to 2.3% depending on cancer type.

Patients with chronic kidney disease (CKD) faced even greater risks, with absolute risks of acute renal AEs ranging from 4.1% to 9.7% when receiving CT scans with iodinated CM, highlighting the need for careful risk assessment in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of renal events following intravenous iodinated contrast material administration among inpatients admitted with cancer a retrospective hospital claims analysis. Ng, CS., Kalva, SP., Gunnarsson, C., et al.[2018]

In a study of 289 cancer patients undergoing iodinated contrast-enhanced CT scans, the use of contrast did not lead to an increase in kidney injury outcomes over a follow-up period of 4 months.

Key risk factors for kidney function deterioration included older age, female sex, and the presence of arterial hypertension, highlighting the importance of these factors in assessing kidney injury risk in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Administration of iodinated contrast: What is the risk in cancer patients? González Cervantes, JJ., Mascarós Martínez, JM., Arana, E.[2021]

A feasibility study involving 10 participants (5 adults and 5 children) demonstrated that using non-contrast kilovoltage (kV) radiographs for online kidney position verification during abdominal radiotherapy is possible and can provide better soft tissue contrast with lower radiation doses (0.1 cGy) compared to conventional megavoltage (MV) imaging (1.7 cGy).

Kidneys were well visualized in 60% of cases, indicating that the effectiveness of this imaging method may depend on individual anatomical factors, suggesting that tailored imaging approaches could enhance the accuracy of kidney positioning during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Online kidney position verification using non-contrast radiographs on a linear accelerator with on board KV X-Ray imaging capability. Willis, DJ., Kron, T., Hubbard, P., et al.[2016]

A 65-year-old man with a 10 cm renal mass and inferior vena cava thrombus underwent successful surgery, including right radical nephrectomy and IVC thrombectomy, with no evidence of cancer recurrence after one year.

Positron emission tomography (PET)/CT was effective in identifying the tumor and thrombus, highlighting its potential role in the evaluation and management of renal cell carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positron emission tomography enhancing tumor thrombus in patient with renal cell carcinoma. Snow, D., Cohen, D., Chapman, WC., et al.[2016]

In a study of 31 patients with renal cell carcinoma (RCC), dual-phase 18F-FDG-PET/CT imaging showed that uptake values and retention index were significantly lower in early-stage tumors compared to more advanced stages, indicating its potential to differentiate tumor aggressiveness.

The study found significant correlations between 18F-FDG uptake and cell proliferation markers, suggesting that dual-phase imaging may be more effective than single-phase imaging in predicting tumor growth and behavior in RCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of cell proliferation in renal cell carcinoma using dual-phase 18F-fluorodeoxyglucose PET/CT. Onishi, R., Noguchi, M., Kaida, H., et al.[2020]

Positron emission tomography-computerized tomography (PET/CT) shows lower sensitivity for diagnosing primary renal masses compared to enhanced computerized tomography, with sensitivity rates for renal cell carcinomas ranging from 31.5% to 77%, but it is more accurate for detecting metastases (94% vs 89%).

The use of (124)I-girentuximab, a targeted radiotracer for clear cell carcinomas, demonstrated a high sensitivity of 86.2% and specificity of 85.9%, indicating its potential for improved diagnosis and treatment selection in renal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic Challenges of Kidney Cancer: A Systematic Review of the Role of Positron Emission Tomography-Computerized Tomography. Gofrit, ON., Orevi, M.[2018]

In a study of 18 patients with renal cell carcinoma (RCC), [68 Ga]Ga-FAPI-04 PET/CT demonstrated significantly higher tumor-to-background ratios (TBR) compared to [18F]F-FDG PET/CT, indicating better imaging performance for detecting lesions (median TBR of 5.6 vs. 2.1, p < 0.001).

The results suggest that [68 Ga]Ga-FAPI-04 PET/CT could serve as a complementary imaging tool for RCC, potentially aiding in prognosis and theranostic applications, as 39% of patients had lesions with high SUVmax values (≥10).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of [68&#160;Ga]Ga-FAPI-04 PET/CT in renal cell carcinoma: a preliminary study. Civan, C., Kuyumcu, S., Has Simsek, D., et al.[2023]

Positron emission tomography (PET) is a valuable imaging tool for cancer, but its effectiveness in renal cell carcinoma (RCC) is limited due to the variable uptake of the common radiotracer, fluorodeoxyglucose (FDG).

Despite these challenges, the variable FDG uptake in RCC may help predict responses to certain targeted therapies, highlighting the potential for PET to aid in characterizing renal masses, staging RCC, and monitoring treatment responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positron emission tomography in renal cell carcinoma: an imaging biomarker in development. Khandani, AH., Rathmell, WK.[2022]

References

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

Development and Validation of a Risk Model for Predicting Contrast-Associated Acute Kidney Injury in Patients With Cancer: Evaluation in Over 46,000 CT Examinations. [2023]

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

The Impact of Radiopharmaceutical Therapy on Renal Function. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Risk of renal events following intravenous iodinated contrast material administration among inpatients admitted with cancer a retrospective hospital claims analysis. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Administration of iodinated contrast: What is the risk in cancer patients? [2021]

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

Online kidney position verification using non-contrast radiographs on a linear accelerator with on board KV X-Ray imaging capability. [2016]

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

Positron emission tomography enhancing tumor thrombus in patient with renal cell carcinoma. [2016]

7. Greece pubmed.ncbi.nlm.nih.gov

Assessment of cell proliferation in renal cell carcinoma using dual-phase 18F-fluorodeoxyglucose PET/CT. [2020]

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

Diagnostic Challenges of Kidney Cancer: A Systematic Review of the Role of Positron Emission Tomography-Computerized Tomography. [2018]

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

The role of [68&#160;Ga]Ga-FAPI-04 PET/CT in renal cell carcinoma: a preliminary study. [2023]

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

Positron emission tomography in renal cell carcinoma: an imaging biomarker in development. [2022]