PET/CT Characterization of Treatment Resistance

Study Overview
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Brief Summary
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This study will use different types of medical imaging to assess how lesions from advanced prostate cancer become resistant to second-generation AR-targeted therapy, and how the different types of imaging compare in that assessment. Participants in this study have advanced prostate cancer and are either scheduled to start a second-generation androgen receptor (AR) targeted therapy (such as enzalutamide, abiraterone, or apalutamide) or are already being treated with one. Participants can expect to be in the study for at least 9 months, and up to 2 years.

Detailed Description
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There are two groups, or cohorts, in this study. Participants are assigned to Cohort A if they have advanced prostate cancer and are scheduled to start a second-generation AR-targeted therapy (such as enzalutamide, abiraterone, or apalutamide) or PSMA directed radiotherapy (e.g. Lu177-PSMA radio-ligand therapy. Participants are assigned to Cohort B if they have advanced prostate cancer, are already on a second-generation AR-targeted therapy, and have shown an increase in their PSA (prostate-specific antigen) levels. There are two medical imaging scans that will be done for research purposes in this study. One is called 18F-fluorodeoxyglucose positron emission tomography (FDG PET) and the other is prostate-specific membrane antigen positron emission tomography (PSMA PET). These scans are done simultaneously with computed tomography (CT) scanning. Participants will be scheduled to have 6 scans, 3 FDG PET/CT scans and 3 PSMA PET/CT scans.

Official Title
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PET/CT Characterization of Treatment Resistance of AR-targeted Therapies in mCRPC

Conditions
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Prostate Cancer

Intervention / Treatment
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* Diagnostic Test: F-fluorodeoxyglucose positron emission tomography (FDG PET)
* Diagnostic Test: prostate-specific membrane antigen positron emission tomography (PSMA PET)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven adenocarcinoma of the prostate. At least 1 radiographic metastases as seen on conventional CT imaging or bone scan Progressive prostate cancer as evident by at least two separate increase in PSA over nadir, and absolute PSA value at least 2 ng/ml (INTRINSIC RESISTANCE COHORT ONLY) Patients must be candidate for a second-generation androgen receptor (AR) inhibitor (e.g. enzalutamide, abiraterone, apalutamide), or Lu177-PSMA radioligand therapy (INTRINSIC RESISTANCE COHORT ONLY) Men of age >18 years. Patients must be able to comply with all study procedures, including having both the ability and willingness to lie flat for ≥ 30 minutes during imaging Patients must be informed of the exploratory nature of the study and its potential risks, and must sign IRB- approved consent form indicating such understanding. Life-expectancy at least 12 months Patients currently receiving a second-generation androgen receptor (AR) inhibitor (e.g. enzalutamide, abiraterone, apalutamide) and must have had 1) PSA decline on treatment and 2) now have PSA increase over nadir while still on treatment (patients must be registered within 12 weeks of first documented PSA increase) (ACQUIRED RESISTANCE COHORT ONLY) Exclusion Criteria: Must not have uncontrolled diabetes (fasting blood sugar > 200 mg/dL or inability to safely hold diabetes medication or fast 6 hours prior to FDG PET scan) Prior treatment with second-generation AR inhibitor for prostate cancer in the metastatic disease setting (prior second-generation AR inhibitor in the neoadjuvant or adjuvant setting is permitted unless patient developed progression while on treatment) (INTRINSIC RESISTANCE COHORT, AR-INHIBITOR GROUP ONLY) Pain or clinical symptoms from metastatic prostate cancer requiring opioid analgesics Known neuro-endocrine prostate cancer Prior radioisotope therapy for castration-resistant prostate cancer To avoid the possibility of unintended coercion, vulnerable populations such as incarcerated subjects, subjects unable to provide their own informed consent and non-English speaking patients will not be considered

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Intrinsic Resistance Cohort (Cohort A)<br>Participants assigned to Cohort A have advanced prostate cancer and are scheduled to start a second-generation AR-targeted (such as enzalutamide, abiraterone, or apalutamide) or PSMA directed (e.g. Lu177-PSMA) therapies . | Diagnostic Test: F-fluorodeoxyglucose positron emission tomography (FDG PET)<br>* Imaging scan<br>Diagnostic Test: prostate-specific membrane antigen positron emission tomography (PSMA PET)<br>* Imaging scan<br>|
| Other: Acquired Resistance Cohort (Cohort B)<br>Participants are assigned to Cohort B if they have advanced prostate cancer, are already on a second-generation AR-targeted therapy, and have shown an increase in their PSA (prostate-specific antigen) levels. | Diagnostic Test: F-fluorodeoxyglucose positron emission tomography (FDG PET)<br>* Imaging scan<br>Diagnostic Test: prostate-specific membrane antigen positron emission tomography (PSMA PET)<br>* Imaging scan<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize intrinsic resistance based on FDG and PSMA PET through change in individual lesion update levels. | Changes in individual lesion update levels (ΔiSUVtotal) will be calculated. SUVtotal is a metric of activity, for which less activity is better. | Baseline to 12 weeks | 
| Characterize change in intrinsic resistance based on FDG and PSMA PET. | Changes in individual lesion update levels (ΔiSUVtotal) will be calculated. SUVtotal is a metric of activity, for which a decrease in activity is better. | Baseline to 12 weeks | 
| Characterize change in intrinsic resistance based on FDG and PSMA PET. | Changes in individual lesion update levels (ΔiSUVtotal) will be calculated. SUVtotal is a metric of activity, for which a decrease in activity is better. | 12 weeks to 36 weeks | 
| Characterize change in intrinsic resistance based on FDG and PSMA PET. | Changes in individual lesion update levels (ΔiSUVtotal) will be calculated. SUVtotal is a metric of activity, for which a decrease in activity is better. | Baseline to 36 weeks | 
| Characterize acquired resistance at the time of progression | Percentage and absolute changes in individual lesion update levels (ΔiSUVtotal) will be calculated. | Baseline to 36 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlate amount of intrinsic resistance on FDG and PSMA PET to predict time to PSA progression | Analysis will be conducted to evaluate whether changes in lesion uptake values predict time to PSA progression. PSA progression will be 25% increase and >2 ng/mL above PSA nadir | Baseline to 36 weeks | 
| Correlate amount of intrinsic resistance on FDG and PSMA PET to predict time to radiographic progression | Analysis will be conducted to evaluate whether changes in lesion uptake values predict time to radiographic progression. Time to radiographic progression will be defined as the number of days to confirmed radiographic progression using Prostate Cancer WorkingGroup 3 (PCWG3) criteria. | Baseline to 36 weeks | 
| Correlate amount of intrinsic resistance on FDG and PSMA PET to predict time duration on treatment | Analysis will be conducted to evaluate whether changes in lesion uptake values predict duration of treatment. Duration of treatment will be defined as the time from treatment start, to treatment discontinuation (and reason for discontinuation) using PCWG3 criteria. | Up to 36 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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androgen receptor targeted therapy, imaging