11C-YJH08 PET Imaging for the Detection of Glucocorticoid Receptor Expression in Patients With Metastatic Prostate Cancer
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
PRIMARY OBJECTIVES:
- 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:
- To determine the safety and determine average organ uptake of 11C-YJH08. (Cohort A and B)
- 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:
- 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort A: 11C-YJH08 with PET/MRI or PET/CT 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
Undergo CT imaging
Other Names:
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
Procedure: Positron Emission Tomography
Undergo PET imaging
Other Names:
Drug: 11C-YJH08
Given IV
Other Names:
|
| Experimental: Cohort B: 11C-YJH08 with additional PET/MRI, PET/CT at progression 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
Undergo CT imaging
Other Names:
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
Procedure: Positron Emission Tomography
Undergo PET imaging
Other Names:
Drug: 11C-YJH08
Given IV
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Sensitivity of 11C-YJH08 PET in metastatic lesion detection (Cohort A only) [Up to day 1 follow-up]
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.
- 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) [Up to 24 months]
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.
- 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) [Up to 24 months]
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.
Secondary Outcome Measures
- Incidence of adverse events [Up to day 1 follow-up]
As recorded by Common Terminology Criteria for Adverse Events Version 5.0 criteria and organ dosimetry of 11C-YJH08 PET. Will be descriptively reported.
- Descriptive patterns of intra-tumoral uptake of 11C-YJH08 on whole body PET [Up to 24 months]
Including by site of disease, uptake by tumor type, inter-tumoral and interpatient heterogeneity, and tumor-to-background signal.
- Association between baseline uptake on 11C-YJH08 PET and objective response rate (Cohort B only) [Up to 24 months]
Will be compared between dichotomized groups using the chi-squared test.
- Association between baseline uptake on 11C-YJH08 PET with progression-free survival (Cohort B only) [Up to 24 months]
The log rank test will be used to compare progression-free survival between dichotomized subgroups.
- Association between baseline uptake on 11C-YJH08 PET with prostate specific antigen (PSA50) response (Cohort B only) [Up to 24 months]
Will be compared between dichotomized groups using the chi-squared test.
Eligibility Criteria
Criteria
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
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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
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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.
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The subject is able and willing to comply with study procedures and provide signed and dated informed consent
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
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Age 18 years or older at the time of study entry
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Serum creatinine =< 1.5 x upper limit of normal (ULN) OR estimated creatinine clearance > 50 ml/min
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Total bilirubin =< 1.5 x ULN
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Hemoglobin >= 8.0 g/dL
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Platelet count >= 50,000/microliter
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Absolute neutrophil count >= 1000/microliter
Exclusion Criteria:
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Patients who because of age, general medical or psychiatric condition, or physiologic status cannot give valid informed consent
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Concurrent treatment with any dose of systemic glucocorticoids within 7 days prior to cycle 1 day 1 (C1D1)
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History of adrenal insufficiency requiring use of systemic glucocorticoid replacement
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History of Cushing's disease or Cushing's syndrome
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Any condition that, in the opinion of the principal investigator, would impair the patient's ability to comply with study procedures
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Contra-indication to MRI (e.g. pacemaker placement, severe claustrophobia) (applicable only for patients scheduled for PET/MRI)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of California San Francisco | San Francisco | California | United States | 94143 |
Sponsors and Collaborators
- Michael Evans
- U.S. Army Medical Research Acquisition Activity
- National Institute of Mental Health (NIMH)
Investigators
- Principal Investigator: Michael Evans, PhD, University of California, San Francisco
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 20926
- NCI-2021-04300
- 5R01MH115043-03