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

Metastatic Prostate Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04927663
• Other study ID #: 20926
• Secondary ID: NCI-2021-043005R
• Status: Recruiting
• Phase: Phase 1
• Start date: August 10, 2021
• Est. completion date: October 31, 2024

Study information

• Verified date: January 2024
• Source: University of California, San Francisco
• Contact: Khadija Siddiqua
• Phone: (310) 794-7329
• Email: khadija.siddiqua[@]ucsf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 25
• Est. completion date: October 31, 2024
• Est. primary completion date: October 31, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Carcinoma
• Castration-Resistant Prostate Carcinoma
• Metastatic Prostate Carcinoma
• Prostatic Neoplasms
• Stage IV Prostate Cancer AJCC v8
• Stage IVA Prostate Cancer AJCC v8
• Stage IVB Prostate Cancer AJCC v8

Intervention

Procedure:
• Computed Tomography
Undergo CT imaging
• Magnetic Resonance Imaging
Undergo MRI
• Positron Emission Tomography
Undergo PET imaging

Drug:
• 11C-YJH08
Given IV

Locations

Country	Name	City	State
United States	University of California San Francisco	San Francisco	California

Sponsors (3)

Lead Sponsor	Collaborator
Michael Evans	National Institute of Mental Health (NIMH), U.S. Army Medical Research Acquisition Activity

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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