11C-YJH08 PET Imaging for Detection of Glucocorticoid Receptor Expression

Solid Tumor 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, 2025

Study information

• Verified date: May 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 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. Systemic 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. (Cohorts B & C). SECONDARY OBJECTIVES: I. To determine the safety and determine average organ uptake of 11C-YJH08. 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. 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. (Cohorts B & C) 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: Participants are assigned to 1 of 3 arms. Cohort A (Dosimetry): Participants 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. **Enrollment in Cohorts B & C will enroll after dosimetry has been established in Cohort A** Cohort B: Participants with mCRPC receive 11C-YJH08 and undergo either PET/MRI or PET/CT at baseline and at time of progression. Cohort C: Participants with solid tumors receive 11C-YJH08 and undergo either PET/MRI or PET/CT at baseline and at time of progression. Participants are assessed the day of the scan for safety follow-up, and up to 24 months for non-interventional clinical outcomes. An optional metastatic tumor biopsy may be performed within 14 days of the initial scan.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 26
• Est. completion date: October 31, 2025
• Est. primary completion date: October 31, 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Disease characteristics by cohort, as defined by:

• COHORT A: Histologically confirmed metastatic solid tumor malignancy.
• COHORT B: Metastatic castration-resistant prostate cancer with progression on systemic therapies by PCWG3.
• COHORT C: Metastatic advanced solid tumor malignancy other than prostate adenocarcinoma with at least one metastasis on conventional imaging.

2. The subject is able and willing to comply with study procedures and provide signed and dated informed consent.

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

4. Age 18 years or older at the time of study entry.

5. Adequate organ function, as defined by:

1. Serum creatinine =< 1.5 x upper limit of normal (ULN) OR estimated creatinine clearance > 50 ml/min

2. Total bilirubin =< 1.5 x ULN

3. Hemoglobin >= 8.0 g/dL

4. Platelet count >= 50,000/microliter

5. Absolute neutrophil count >= 1000/microliter

Exclusion Criteria:

1. Patients who because of age, general medical or psychiatric condition, or physiologic status cannot give valid informed consent.

2. Concurrent treatment with any dose of systemic glucocorticoids within 7 days prior to cycle 1 day 1 (C1D1).

3. History of adrenal insufficiency requiring use of systemic glucocorticoid replacement.

4. History of Cushing's disease or Cushing's syndrome.

5. Any condition that, in the opinion of the principal investigator, would impair the patient's ability to comply with study procedures.

6. 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 Castration-resistant Prostate Cancer
• Metastatic Prostate Carcinoma
• Neoplasms
• Prostatic Neoplasms
• Solid Tumor
• Solid Tumor, Adult
• 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

Procedure:
• Optional Tumor Biopsy
Optional procedure to obtain tumor tissue

Locations

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

Sponsors (3)

Lead Sponsor	Collaborator
Rahul Aggarwal	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)	Using as a cut-off to define a positive lesion on PET as a lesion with SUV at least 1.5 times higher than mediastinal blood pool, the sensitivity (probability that a test will indicate recurrent disease among those with recurrent disease (True Positive / (True Positive + False Negative)) 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	Median percent change from baseline in standardized uptake value (SUV)max (Cohort B and C only)	The median percent change from baseline, and range of SUVmax (across all metastatic lesions per patient) will be descriptively reported using mediastinal blood pool and normal organ as background uptake values.	Up to 24 months
Primary	Median percent change from baseline at the time of progression in standardized uptake value (SUV)max-ave (Cohort B and C only)	The median percent change from baseline, and range of SUVmax-ave (in each study cohort) will be descriptively reported using mediastinal blood pool and normal organ as background uptake values.	Up to 24 months
Secondary	Number of participants with reported treatment-emergent adverse events	The frequency and severity of adverse events following 11C-YJH08 injection will be descriptively reported, using NCI Common Terminology Criteria for Adverse Events Version 5.0 criteria.	Up to day 1 after injection
Secondary	Median intra-tumoral uptake	The median and range for intra-tumoral SUVmax within metastatic lesions will be descriptively reported to asses for intra-tumoral heterogeneity and differences in uptake by site of disease.	Up to 24 months
Secondary	Association between baseline uptake on 11C-YJH08 PET with prostate specific antigen (PSA50) response (Cohort B only )	The association between baseline and percent change from baseline in SUVmax-ave with the cohort will be dichotomized above and below the median will be compared to the PSA response rate using Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria	Up to 24 months
Secondary	Association between baseline uptake on 11C-YJH08 PET and objective response rate (Cohort B & C only)	The association between baseline and percent change from baseline in SUVmax-ave with the cohort will be dichotomized above and below the median will be compared to the objective response rate (in subset of measurable tumors by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1)	Up to 24 months
Secondary	Association between baseline uptake on 11C-YJH08 PET and clinical benefit rate (Cohort B & C only)	The association between baseline and percent change from baseline in SUVmax-ave with the cohort will be dichotomized above and below the median will be compared to the clinical benefit rate (in subset of measurable tumors by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1)	Up to 24 months
Secondary	Median progression-free survival by cohort (Cohort B & C only)	The association between baseline and percent change from baseline in SUVmax-ave with the cohort will be dichotomized above and below the median and median progression-free survival will be reported by group.	Up to 24 months