[18F]PT2385 PET/CT in Patients With Renal Cell Carcinoma
Study Details
Study Description
Brief Summary
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 two 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
HIF2α is an emerging therapeutic target in RCC. Proof-of-principle experiments in mice have demonstrated the feasibility of PET/CT imaging with novel radiotracers, [11C] and [18F]PT2385, to assess HIF2α expression in RCC. [18F]PT2385 has been proposed in this study for practical imaging of HIF2α.
This is a non-therapeutic research study. Patients with localized or metastatic RCC will undergo imaging with [18F]PT2385. Patients will have the opportunity to ask questions regarding the procedure. A peripheral intravenous line will be placed for [18F]PT2385 administration. Patients will be injected with [18F]PT2385 intravenously and evaluated by PET/CT.
Up to 10 subjects will undergo a dynamic PET scanning and multi-time point whole body imaging to determine the intratumoral tracer kinetics, the optimal time point for whole body imaging, as well as to calculate human dosimetry. In the first 3 subjects, a dynamic scan over the kidneys will be performed for approximately 25 minutes. Upon completion of the dynamic scan, a whole-body scan will be acquired to yield a whole body distribution at approximately 35 minutes. These 3 subjects will be asked to return for delayed whole body images at 120 and 240 minutes post injection. In up to 7 additional subjects, a dynamic scan will be acquired for 55 minutes followed by an immediate whole body scan to yield whole body distribution at approximately 65 minutes. Additional whole-body images will be acquired at 120 and 240 minutes post-injection.
The pre-surgical cohort of 20 subjects will receive one PET/CT scan at the optimal time point determined from the first 10 subjects. Subsequently, surgery will be performed and SUV from the PET scans will be correlated with HIF2α levels by IHC on the surgical specimen.
A second cohort of 20 subjects with metastatic RCC will be evaluated. Patients with metastatic disease should all have a previous tissue diagnosis, and this cohort will focus on ccRCC patients. Subjects with metastatic ccRCC will be injected with [18F]PT2385 by intravenous (IV) push and will have a whole-body [18F]PT2385 PET/CT at a time considered optimal based on imaging studies performed in cohort 1. A mandatory biopsy will be performed, and up to 4 suitable core tissue samples will be obtained.
Following dosimetry studies, a subset of patients may undergo repeat [18F]PT2385 PET studies.
Patients in both cohorts will receive standard or experimental treatment for RCC at the discretion of the treating physician.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Pre-Surgical Patients with suspected RCC planned for surgery |
Drug: [18F]PT2385
[18F]PT2385 infusion
Procedure: Positron Emission Tomography/Computed Tomography
PET/CT scan after [18F]PT2385 infusion
Other Names:
|
| Experimental: Metastatic Patients with metastatic ccRCC |
Drug: [18F]PT2385
[18F]PT2385 infusion
Procedure: Positron Emission Tomography/Computed Tomography
PET/CT scan after [18F]PT2385 infusion
Other Names:
Procedure: Biopsy
CT-guided tumor biopsy
|
Outcome Measures
Primary Outcome Measures
- Correlation between [18F]PT2385 and HIF2α [Up to 5 years]
Correlation between [18F]PT2385 PET avidity and HIF2α expression in primary tumors
- Correlation between [18F]PT2385 and HIF2α IHC [Up to 5 years]
Correlation between [18F]PT2385 PET avidity and HIF2α expression by IHC
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients with suspected primary RCC with planned surgery (cohort 1) or patients with tissue-confirmed metastatic ccRCC with a site accessible for biopsy (cohort 2). (In standard clinical practice, biopsy is not routinely performed in patients who will be having surgery).
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Ability to understand and the willingness to sign a written informed consent that includes study interventions (PET/CT and, if cohort 2, mandatory biopsy).
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Ability to lie still for a 30- to 60-minute PET/CT scan.
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One of the following:
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Cohort 1. Patients with suspected RCC planned for surgery.
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Cohort 2. Patients with metastatic ccRCC.
- Women of child-bearing potential must agree to undergo and have documented a negative pregnancy test on the day of [18F]PT2385 administration. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or celibate by choice) who meets the following criteria:
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Has not undergone a hysterectomy or bilateral oophorectomy; or
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Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
Exclusion Criteria:
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Uncontrolled severe and irreversible intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements.
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Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
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Claustrophobia or other contraindications to PET/CT.
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Subjects must not weigh more than the maximum weight limit for the table for the PET/CT scanner where the study is being performed (>200 kilograms or 440 pounds).
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For cohort 2 patients, lack of suitable sites for mandatory biopsy. For example, patients with metastatic disease restricted to the lungs that would require percutaneous biopsies with associated risk of bleeding and pneumothorax will be excluded.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UT Southwestern Medical Center | Dallas | Texas | United States | 75390 |
Sponsors and Collaborators
- Neil M Rofsky, MD, MHA
Investigators
- Principal Investigator: James Brugarolas, MD, PhD, UT Southwestern Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- STU-2021-0592