11C-YJH08 PET Imaging for the Detection of Glucocorticoid Receptor Expression in Patients With Metastatic Prostate Cancer

Study Overview
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Brief Summary
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This phase I trial studies if positron emission tomography (PET) imaging using 11C-YJH08 can be useful for detecting certain cell receptor expression in tumor cells in patients with prostate cancer that has spread to other parts of the body (metastatic). 11C-YJH08 is a small-molecule radiotracer that binds to receptors on cells (glucocorticoid receptor) so that they show up better on the PET scan. Anti-hormone therapy (including enzalutamide) can cause more glucocorticoid receptors to be produced in tumor cells, which can make the tumor cells resist hormone therapies. If researchers can find a better way to detect whether glucocorticoid receptors are increasing during therapy, it may lead to more successful therapies using glucocorticoid receptor antagonists.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine the feasibility of metastatic lesion detection in enzalutamide/apalutamide-resistant metastatic castration-resistant prostate cancer (mCRPC) using 11C-YJH08 PET. (Cohort A) II. To determine the mean percent change from baseline at the time of progression on enzalutamide or apalutamide in standardized uptake value (SUV)max-ave on paired 11C-YJH08 PET on a per-patient and per-lesion basis. (Cohort B) SECONDARY OBJECTIVES: I. To determine the safety and determine average organ uptake of 11C-YJH08. (Cohort A and B) II. To descriptively report the patterns of intra-tumoral uptake of 11C-YJH08 on whole body PET, including by site of disease, uptake by tumor type, inter-tumoral and inter-patient heterogeneity, and tumor-to-background signal. (Cohort A and B) III. To determine whether baseline uptake on 11C-YJH08 PET is associated with subsequent clinical outcomes including objective response rate, progression-free survival, and prostate specific antigen (PSA50) response. (Cohort B) EXPLORATORY OBJECTIVE: I. To determine the association between uptake on 11C-YJH08 PET with glucocorticoid receptor (GR) expression and transcriptional signature scores on paired metastatic tumor biopsies. OUTLINE: Patients are assigned to 1 of 2 arms. ARM I: Patients receive 11C-YJH08 intravenously (IV) over 1-2 minutes and 10-60 minutes later, undergo either PET/magnetic resonance imaging (MRI) or PET/computed tomography (CT) over 90 minutes at baseline. ARM II: Patients receive 11C-YJH08 IV over 1-2 minutes and 10-60 minutes later, undergo either PET/MRI or PET/CT over 90 minutes at baseline and at time of disease progression. After completion of study treatment, patients are followed up on day 1.

Official Title
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A First-in-Human, Phase I PET Imaging Study of 11C-YJH08, a Selective Glucocorticoid Receptor-Targeting Agent, in Patients With Advanced Solid Tumor Malignancies

Conditions
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Castration-Resistant Prostate Carcinoma, Metastatic Prostate Carcinoma, Stage IV Prostate Cancer AJCC v8, Stage IVA Prostate Cancer AJCC v8, Stage IVB Prostate Cancer AJCC v8

Intervention / Treatment
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* Procedure: Computed Tomography
* Procedure: Magnetic Resonance Imaging
* Procedure: Positron Emission Tomography
* Drug: 11C-YJH08


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: COHORT A: Histologically-confirmed progressive metastatic castration resistant prostate cancer with evidence of progression by the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) on current enzalutamide, apalutamide, or darolutamide treatment at the time of study entry COHORT B: Metastatic castration-resistant prostate cancer with planned treatment with enzalutamide, apalutamide, or or darolutamide as next line of systemic therapy at the time of study entry. Patients must not have received first dose of enzalutamide, apalutamide, or or darolutamide prior to baseline 11C-YJH08 PET Patients in Cohort A and B must have serum testosterone level < 50 ng/dL and must remain on luteinizing hormone-releasing hormone (LHRH) analog therapy for the duration of study participation, in the absence of prior bilateral orchiectomy. If testosterone level is pending at the time of baseline Positron Emission Tomography (PET), it is permissible to proceed with baseline PET, provided there is documentation of continuous Luteinizing hormone-releasing hormone (LHRH) analog treatment in the preceding 3 months. The subject is able and willing to comply with study procedures and provide signed and dated informed consent Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Age 18 years or older at the time of study entry Serum creatinine =< 1.5 x upper limit of normal (ULN) OR estimated creatinine clearance > 50 ml/min Total bilirubin =< 1.5 x ULN Hemoglobin >= 8.0 g/dL Platelet count >= 50,000/microliter Absolute neutrophil count >= 1000/microliter Exclusion Criteria: Patients who because of age, general medical or psychiatric condition, or physiologic status cannot give valid informed consent Concurrent treatment with any dose of systemic glucocorticoids within 7 days prior to cycle 1 day 1 (C1D1) History of adrenal insufficiency requiring use of systemic glucocorticoid replacement History of Cushing's disease or Cushing's syndrome Any condition that, in the opinion of the principal investigator, would impair the patient's ability to comply with study procedures Contra-indication to MRI (e.g. pacemaker placement, severe claustrophobia) (applicable only for patients scheduled for PET/MRI)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A: 11C-YJH08 with PET/MRI or PET/CT<br>Patients receive approximately 20 millicurie (mCi) of 11C-YJH08 IV over 1-2 minutes and 10-60 minutes later, undergo either PET/MRI or PET/CT over 90 minutes at baseline. | Procedure: Computed Tomography<br>* Undergo CT imaging<br>* Other names: CT Scan;Procedure: Magnetic Resonance Imaging<br>* Undergo MRI<br>* Other names: Nuclear Magnetic Resonance Imaging;Procedure: Positron Emission Tomography<br>* Undergo PET imaging<br>* Other names: proton magnetic resonance spectroscopic imaging;Drug: 11C-YJH08<br>* Given IV<br>* Other names: Radioactive Label;|
| Experimental: Cohort B: 11C-YJH08 with additional PET/MRI, PET/CT at progression<br>Patients receive approximately 20 mCi of 11C-YJH08 IV over 1-2 minutes and 10-60 minutes later, undergo either PET/MRI or PET/CT over 90 minutes at baseline and at time of disease progression. | Procedure: Computed Tomography<br>* Undergo CT imaging<br>* Other names: CT Scan;Procedure: Magnetic Resonance Imaging<br>* Undergo MRI<br>* Other names: Nuclear Magnetic Resonance Imaging;Procedure: Positron Emission Tomography<br>* Undergo PET imaging<br>* Other names: proton magnetic resonance spectroscopic imaging;Drug: 11C-YJH08<br>* Given IV<br>* Other names: Radioactive Label;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity of 11C-YJH08 PET in metastatic lesion detection (Cohort A only) | Will be descriptively reported on a lesion-per-lesion basis, using as reference standard staging scans including computed tomography or magnetic resonance imaging of the chest/abdomen/pelvis. | Up to day 1 follow-up | 
| Mean percent change from baseline at the time of progression in standardized uptake value (SUV)max-ave on paired 11C-YJH08 PET per-patient basis (Cohort B only) | Will be descriptively reported along with range on a per-patient basis. Wilcoxon signed rank test will be used to compare the follow up to baseline PET scan values at patient level. | Up to 24 months | 
| Mean percent change from baseline at the time of progression in standardized uptake value (SUV)max-ave on paired 11C-YJH08 PET per-lesion (Cohort B only) | Will be descriptively reported along with range on a per-lesion basis. Wilcoxon signed rank test will be used to compare the follow up to baseline PET scan values at lesion level. | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events | As recorded by Common Terminology Criteria for Adverse Events Version 5.0 criteria and organ dosimetry of 11C-YJH08 PET. Will be descriptively reported. | Up to day 1 follow-up | 
| Descriptive patterns of intra-tumoral uptake of 11C-YJH08 on whole body PET | Including by site of disease, uptake by tumor type, inter-tumoral and interpatient heterogeneity, and tumor-to-background signal. | Up to 24 months | 
| Association between baseline uptake on 11C-YJH08 PET and objective response rate (Cohort B only) | Will be compared between dichotomized groups using the chi-squared test. | Up to 24 months | 
| Association between baseline uptake on 11C-YJH08 PET with progression-free survival (Cohort B only) | The log rank test will be used to compare progression-free survival between dichotomized subgroups. | Up to 24 months | 
| Association between baseline uptake on 11C-YJH08 PET with prostate specific antigen (PSA50) response (Cohort B only) | Will be compared between dichotomized groups using the chi-squared test. | Up to 24 months |