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

Phase 1

Terminated

Conditions: Stage IVA Prostate Cancer AJCC v8
Stage IVB Prostate Cancer AJCC v8
Metastatic Castration-resistant Prostate Cancer
Castration-Resistant Prostate Carcinoma
Stage IV Prostate Cancer AJCC v8
Metastatic Prostate Carcinoma
Solid Tumor, Adult
Solid Tumor

Interventions: Procedure: Computed Tomography
Procedure: Magnetic Resonance Imaging
Procedure: Positron Emission Tomography
Drug: 11C-YJH08
Procedure: Optional Tumor Biopsy

Registration Number: NCT04927663

Lead Sponsor: Rahul Aggarwal

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 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.

Detailed 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 & Eligibility

Status: TERMINATED

Sex: Male

Target Recruitment: 2

Inclusion Criteria

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 Prostate Specific Antigen Working Group 3 (PSAWG3).
- COHORT C: Metastatic advanced solid tumor malignancy other than prostate adenocarcinoma with at least one metastasis on conventional imaging.
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.
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

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).

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort A: Any Solid Tumor (Dosimetry Cohort)	Computed Tomography	Participants with any solid tumor malignancy with evidence of one or more metastases will 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.
Cohort A: Any Solid Tumor (Dosimetry Cohort)	Magnetic Resonance Imaging	Participants with any solid tumor malignancy with evidence of one or more metastases will 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.
Cohort A: Any Solid Tumor (Dosimetry Cohort)	Positron Emission Tomography	Participants with any solid tumor malignancy with evidence of one or more metastases will 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.
Cohort A: Any Solid Tumor (Dosimetry Cohort)	Optional Tumor Biopsy	Participants with any solid tumor malignancy with evidence of one or more metastases will 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.
Cohort B: Metastatic CRPC	Computed Tomography	Participants with metastatic CRPC will 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 optional repeat scan at the time of progression.
Cohort B: Metastatic CRPC	Magnetic Resonance Imaging	Participants with metastatic CRPC will 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 optional repeat scan at the time of progression.
Cohort B: Metastatic CRPC	Positron Emission Tomography	Participants with metastatic CRPC will 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 optional repeat scan at the time of progression.
Cohort B: Metastatic CRPC	Optional Tumor Biopsy	Participants with metastatic CRPC will 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 optional repeat scan at the time of progression.
Cohort C: Solid Tumor Malignancy	Computed Tomography	Participants with any solid tumor malignancies other than prostate adenocarcinoma with one or more metastases on conventional imaging will 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 optional repeat scan at the time of progression.
Cohort C: Solid Tumor Malignancy	Magnetic Resonance Imaging	Participants with any solid tumor malignancies other than prostate adenocarcinoma with one or more metastases on conventional imaging will 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 optional repeat scan at the time of progression.
Cohort C: Solid Tumor Malignancy	Positron Emission Tomography	Participants with any solid tumor malignancies other than prostate adenocarcinoma with one or more metastases on conventional imaging will 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 optional repeat scan at the time of progression.
Cohort C: Solid Tumor Malignancy	Optional Tumor Biopsy	Participants with any solid tumor malignancies other than prostate adenocarcinoma with one or more metastases on conventional imaging will 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 optional repeat scan at the time of progression.
Cohort A: Any Solid Tumor (Dosimetry Cohort)	11C-YJH08	Participants with any solid tumor malignancy with evidence of one or more metastases will 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.
Cohort B: Metastatic CRPC	11C-YJH08	Participants with metastatic CRPC will 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 optional repeat scan at the time of progression.
Cohort C: Solid Tumor Malignancy	11C-YJH08	Participants with any solid tumor malignancies other than prostate adenocarcinoma with one or more metastases on conventional imaging will 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 optional repeat scan at the time of progression.

Primary Outcome Measures

Name	Time	Method
Median Percent Change From Baseline in Standardized Uptake Value (SUV)Max (Cohort B and C Only)	Up to 24 months	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.
Median Percent Change From Baseline at the Time of Progression in Standardized Uptake Value (SUV)Max-ave (Cohort B and C Only)	Up to 24 months	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.
Sensitivity of 11C-YJH08 PET in Metastatic Lesion Detection (Cohort A Only)	Up to day 1 follow-up	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.

Secondary Outcome Measures

Name	Time	Method
Median Intra-tumoral Uptake	Up to 24 months	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.
Association Between Baseline Uptake on 11C-YJH08 PET With Prostate Specific Antigen (PSA50) Response (Cohort B Only )	Up to 24 months	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
Number of Participants With Reported Treatment-emergent Adverse Events	Up to day 1 after injection	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.
Association Between Baseline Uptake on 11C-YJH08 PET and Objective Response Rate (Cohort B & C Only)	Up to 24 months	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)
Association Between Baseline Uptake on 11C-YJH08 PET and Clinical Benefit Rate (Cohort B & C Only)	Up to 24 months	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)
Median Progression-free Survival by Cohort (Cohort B & C Only)	Up to 24 months	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.