68Ga-PSMA-11 PET/CT for the Diagnosis of Bone Metastases in Patients With Prostate Cancer and Biochemical Progression During Androgen Deprivation Therapy

Study Overview
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Brief Summary
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This phase II trial studies how well 68Ga-PSMA-11 positron emission tomography (PET)/computed tomography (CT) works in detecting the spread of cancer to the bones (bone metastasis) in patients with prostate cancer and increased PSA after treatment (biochemical recurrence) during androgen deprivation therapy. Diagnostic procedures, such as 68Ga-PSMA-11 PET/CT, may help find and diagnose prostate cancer and find out how far the disease has spread.

Detailed Description
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PRIMARY OBJECTIVE: I. To compare the per-patient detection rate of 68Ga-PSMA-11 PET/CT versus bone scan (BS)/CT for M1b in patients treated with androgen deprivation therapy (ADT) who are referred for the imaging evaluation of disease progression. SECONDARY OBJECTIVES: I. To compare the number of lesions rated as positive for bone metastases between the two imaging tests. II. To compare the detection rate of 68Ga-PSMA PET/CT versus BS/CT for all M1 disease (M1a or M1b or M1c). III. To compare the positive predictive value (PPV) per-patient in patients with lesion validation (follow-up imaging or biopsy). OUTLINE: Patients receive gallium Ga 68 gozetotide intravenously (IV). After 50-100 minutes, patients undergo whole body PET/CT.

Official Title
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Head-to-Head Comparison of 68Ga-PSMA-11 PET/CT With 99mTc-MDP Bone Scan and CT for Detection of M1b Disease in Prostate Cancer Patients With Biochemical Progression During ADT

Conditions
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Biochemically Recurrent Prostate Carcinoma, Metastatic Malignant Neoplasm in the Bone, Metastatic Prostate Carcinoma, Stage IV Prostate Cancer American Joint Committee on Cancer (AJCC) v8, Stage IVA Prostate Cancer AJCC v8, Stage IVB Prostate Cancer AJCC v8

Intervention / Treatment
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* Procedure: Computed Tomography
* Other: Gallium Ga 68 Gozetotide
* Procedure: Positron Emission Tomography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with biochemical progression during ADT or combination therapies including ADT who are referred for imaging evaluation (prostate specific antigen [PSA] level >= 1 ng/ml that has increased on at least 2 successive occasions at least 1 weak apart) Patients with bone scan scheduled or performed Within 30 days of the PSMA PET, without any new prostate cancer (PCa) therapy in between Bone scans performed at University of California, Los Angeles (UCLA) and external institutions are eligible if Digital Imaging and Communications in Medicine (DICOM) images can be obtained, imported, and anonymized Patients enrolled in other clinical trials are eligible if they satisfy all other criteria of eligibility Patients or their legal representatives must have the ability to read, understand and provide written informed consent Exclusion Criteria: Initiation of a new therapy between the PSMA PET/CT and the bone scans Inability to provide written informed consent Known inability to remain still and lie flat for duration of each imaging procedure (about 30 minutes)

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diagnostic (68Ga-PSMA-11 PET/CT)<br>Patients receive gallium Ga 68 gozetotide IV. After 50-100 minutes, patients undergo whole body PET/CT. | Procedure: Computed Tomography<br>* Undergo PET/CT<br>* Other names: tomography;Other: Gallium Ga 68 Gozetotide<br>* Given IV<br>* Other names: PSMA-HBED-CC GA-68;Procedure: Positron Emission Tomography<br>* Undergo PET/CT<br>* Other names: proton magnetic resonance spectroscopic imaging;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Per-patient detection rate of gallium Ga 68 gozetotide (68Ga-PSMA-11) positron emission tomography (PET)/computed tomography (CT) | 68Ga-PSMA-11 PET will be compared to bone scan/CT for M1b disease in prostate cancer patients progressing during androgen deprivation therapy. Patients who have at least one positive bone lesion will be rated positive. Patients will be treated as binary categorization. The analysis of the primary objective will utilize the McNemar's test to compare the detection rate between the imaging techniques. | Up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of lesions found by PSMA PET and bone scan + CT | Will be compared using a paired samples t-test. | Up to 4 years | 
| Rate of M1 detection | Will be compared between the two modalities, defined as the number of patients with positive finding(s) for M1 disease (M1a or M1b or M1c), will utilize the McNemar's test for paired proportions. | Up to 4 years | 
| Per-patient positive predictive value (PPV) | Per-patient PPV estimates (with 95% confidence interval), defined as the number true positive findings the total number of positive cases (TP + FP). The lesions will be considered true positive on the basis of biopsy information, follow-up imaging, or changes in prostate specific antigen (PSA) levels. This information will only be available in a small subset of patients. | Up to 4 years | 
| PSA progression-free survival (PFS) | Univariate Cox proportional hazards models for PFS will be constructed with models containing various patient characteristics as well as PSMA PET parameters and bone scan parameters. Hazard ratios with 95% confidence intervals as well as p-values will be tabulated. Next, will explore multivariate models (using LASSO variable selection) including terms for important baseline characteristics as well as PSMA parameters or bone scan parameters and will extract the survival concordance indices from each of these models and compare them. | Up to 4 years | 
| Overall survival (OS) | Univariate Cox proportional hazards models for OS will be constructed with models containing various patient characteristics as well as PSMA PET parameters and bone scan parameters. Hazard ratios with 95% confidence intervals as well as p-values will be tabulated. Next, will explore multivariate models (using LASSO variable selection) including terms for important baseline characteristics as well as PSMA parameters or bone scan parameters and will extract the survival concordance indices from each of these models and compare them. | Up to 4 years | 
| Incidence of adverse events | Assessed using Common Terminology Criteria for Adverse Events version 4.03. | Up to 4 years |