Clinical trial NCT04927663: 11C-YJH08 PET Imaging for Detection of Glucocorticoid Receptor Expression
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: 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
Solid Tumor, Adult
Solid Tumor
Metastatic Castration-resistant Prostate Cancer
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: U.S. Army Medical Research Acquisition Activity
name: National Institute of Mental Health (NIMH)
First posted: 2021-06-16
Enrollment: 2
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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 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.
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).

Primary outcomes:
measure: Sensitivity of 11C-YJH08 PET in Metastatic Lesion Detection (Cohort A Only)
timeFrame: Up to day 1 follow-up
measure: Median Percent Change From Baseline in Standardized Uptake Value (SUV)Max (Cohort B and C Only)
timeFrame: Up to 24 months
measure: Median Percent Change From Baseline at the Time of Progression in Standardized Uptake Value (SUV)Max-ave (Cohort B and C Only)
timeFrame: Up to 24 months
Secondary outcomes:
measure: Number of Participants With Reported Treatment-emergent Adverse Events
timeFrame: Up to day 1 after injection
measure: Median Intra-tumoral Uptake
timeFrame: Up to 24 months
measure: Association Between Baseline Uptake on 11C-YJH08 PET With Prostate Specific Antigen (PSA50) Response (Cohort B Only )
timeFrame: Up to 24 months
measure: Association Between Baseline Uptake on 11C-YJH08 PET and Objective Response Rate (Cohort B & C Only)
timeFrame: Up to 24 months
measure: Association Between Baseline Uptake on 11C-YJH08 PET and Clinical Benefit Rate (Cohort B & C Only)
timeFrame: Up to 24 months
measure: Median Progression-free Survival by Cohort (Cohort B & C Only)
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Rahul Aggarwal, MD
role: PRINCIPAL_INVESTIGATOR
References: