Castration-Resistant Prostate Carcinoma, Metastatic Castration-resistant Prostate Cancer, Metastatic Prostate Carcinoma, Solid Tumor, Solid Tumor, Adult, Stage IVA Prostate Cancer AJCC v8, Stage IVB Prostate Cancer AJCC v8, Stage IV Prostate Cancer AJCC v8
Conditions
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.
Interventions
PROCEDUREComputed Tomography
Undergo CT imaging
PROCEDUREMagnetic Resonance Imaging
Undergo MRI
PROCEDUREPositron Emission Tomography
Undergo PET imaging
DRUG11C-YJH08
Given IV
PROCEDUREOptional Tumor Biopsy
Optional procedure to obtain tumor tissue
Sponsors
U.S. Army Medical Research Acquisition Activity
National Institute of Mental Health (NIMH)
Rahul Aggarwal
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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. |
| 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. |
| 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 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 |
Countries
United States
Participant flow
Pre-assignment details
Only 2 participants were enrolled to Cohort A. The study was closed for slow accrual before enrollment in Cohort B or Cohort C could begin
Participants by arm
| Arm | Count |
|---|---|
| Cohort A: Any Solid Tumor (Dosimetry Cohort) 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. | 2 |
| Cohort B: Metastatic CRPC 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. | 0 |
| Cohort C: Solid Tumor Malignancy 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. | 0 |
| Total | 2 |
Baseline characteristics
| Characteristic | Total | Cohort A: Any Solid Tumor (Dosimetry Cohort) |
|---|---|---|
| Age, Customized 70-79 years | 1 Participants | 1 Participants |
| Age, Customized 80-89 years | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants |
| Region of Enrollment United States | 2 participants | 2 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 2 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 2 | 0 / 0 | 0 / 0 |
Outcome results
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.
Time frame: Up to 24 months
Population: No participants were enrolled in Cohort B or C
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.
Time frame: Up to 24 months
Population: No participants were enrolled in Cohort B or C.
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.
Time frame: Up to day 1 follow-up
Population: Data not collected. Per the pre-specified statistical analysis plan outlined in the study protocol, a sample size of approximately 6 patients for Cohort A is required to collect sufficient data to ensure adequate organ dosimetry and determination of the optimal uptake time following administration of 11C-YJH08.
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)
Time frame: Up to 24 months
Population: No participants were enrolled in Cohorts B or C
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)
Time frame: Up to 24 months
Population: No participants were enrolled in Cohort B or C
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
Time frame: Up to 24 months
Population: No participants were enrolled in Cohort B
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.
Time frame: Up to 24 months
Population: Data not collected. Per the pre-specified statistical analysis plan outlined in the study protocol, a sample size of approximately 6 patients for Cohort A is required to collect sufficient data to ensure adequate organ dosimetry and determination of the optimal uptake time following administration of 11C-YJH08.
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.
Time frame: Up to 24 months
Population: No participants were enrolled in Cohort B or C
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.
Time frame: Up to day 1 after injection
Population: No participants were enrolled in Cohort B or C
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A: Any Solid Tumor (Dosimetry Cohort) | Number of Participants With Reported Treatment-emergent Adverse Events | 0 Participants |
| Cohort C: Solid Tumor Malignancy | Number of Participants With Reported Treatment-emergent Adverse Events | 0 Participants |
| Cohort C: Solid Tumor Malignancy | Number of Participants With Reported Treatment-emergent Adverse Events | 0 Participants |