Comparison Study of PET/CT or PET/MRI Imaging to Magnetic Resonance Imaging (MRI) Alone in Men With Prostate Cancer

Study Overview
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Brief Summary
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This is a study primarily comparing Magnetic Resonance Imaging (MRI) alone to Positron Emission Tomography (PET)/MRI using an experimental tracer, 68Ga-PSMA-HBED-CC, among men with prostate cancer or prostatic cancer recurrence/metastasis. It is hypothesized that this comparison will demonstrate that PET using the tracer, 68Ga-PSMA-HBED-CC, is more sensitive than MRI alone. Potential subjects who cannot undergo MRI may undergo PET/CT instead.

Detailed Description
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This is a multi-reader methodological study comparing the diagnostic value of 68Ga-PSMA-HBED-CC PET/CT or 68Ga-PSMA-HBED-CC PET/MRI over MRI alone, using histologic confirmation or serial follow-up for up to 2 years as the gold standard for determination of primary prostate cancer or prostatic cancer recurrence/metastasis. It is hypothesized that this will demonstrate the superiority of 68Ga-PSMA-HBED-CC PET to MRI for sensitivity, and the non-inferiority of 68Ga-PSMA-HBED-CC PET to MRI for specificity.This is a paired, case-control design that is appropriate to statistically evaluate the difference in sensitivity and specificity between the two imaging modalities. Therefore, the estimation of population prevalence is not a study objective, and estimation of clinical utility through calculation of positive and negative predictive values is not appropriate. Imaging studies and follow up subject scans will be organized so that a panel of independent readers will evaluate the MRI and PET studies to assess the level of suspicion for prostate cancer.

Official Title
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A Phase 2 Comparison Study of 68Ga-PSMA-HBED-CC Positron Emission Tomography (PET)/CT or PET/MRI Imaging to Magnetic Resonance Imaging (MRI) Alone in Men With Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: PET/MRI with Gallium-68 labeled PSMA-HBED-CC
* Drug: Multiple PET/MRI with Gallium-68 labeled PSMA-HBED-CC
* Drug: PET/CT with Gallium-68 labeled PSMA-HBED-CC


Participation Criteria
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Eligibility Criteria
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Male aged 21 years or older. Ability to provide signed informed consent and willingness to comply with protocol requirements. Pathologic confirmation of adenocarcinoma of the prostate gland or high clinical suspicion (PSA > 4 ng/mL, or PSA density > 0.15 ng/mL2, or PSA doubling time < 2 years). Meet one of the following 5 criteria Planned for surgical extirpation, which may or may not include lymph node dissection (high risk primary disease) Planned for targeted biopsy of primary lesion Conventional imaging equivocal or suggestive of prostate cancer metastasis/es Planned focal therapy (with or without radiation therapy) with serial follow-up Elevated PSA with no conventional imaging suggestive of metastatic or recurrent disease a. If part of PET/MRI cohort, subject will undergo clinically indicated MRI imaging prior to treatment. Or b. If part of PET/CT cohort, subject will have had clinically indicated MRI within 3 months prior to treatment. Participants must agree to use an acceptable form of birth control throughout the study period. Participants must use condoms for a period of seven days after each injection, if engaged in sexual activity. Exclusion Criteria: Clinical and/or technical factors that would compromise statistical analysis of the PET and/or MRI. If part of PET/MRI cohort and patient cohort 3 or 5, subject does not plan to have a prescribed abdomen and pelvis MRI If part of PET/MRI cohort and patient cohort 1, 2 or 4, subject does not plan to have a prescribed pelvis MRI If part of PET/CT cohort and patient cohort 3 or 5, subject does not have previous MR imaging of abdomen and pelvis If part of PET/CT cohort and patient cohort 1, 2 or 4, subject does not have previous MR imaging of pelvis If part of PET/CT cohort, investigator review determines that previous MR images do not meet institutional quality standards If part of PET/MRI cohort, contraindications to MRI Contraindications to PSMA IV administration Other unspecified reasons that, in the opinion of investigators, make the subject unsuitable for enrollment

Ages Eligible for Study
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Minimum Age: 21 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: Screening
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects may be assigned to one of three groups, each with a different intervention in terms of either mode or frequency
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PET/MRI<br>PET/MRI with Gallium-68 labeled PSMA-HBED-CC: Subjects will have one visit during which they will undergo a PET/MRI after being injected with the study drug, Gallium-68 labeled PSMA-HBED-CC. | Drug: PET/MRI with Gallium-68 labeled PSMA-HBED-CC<br>* Subjects have one visit, during which they will undergo one PET/MRI with the study drug, Gallium-68 labeled PSMA-HBED-CC, a radiopharmaceutical<br>|
| Experimental: Multiple PET/MRI<br>Multiple PET/MRI with Gallium-68 labeled PSMA-HBED-CC: Subjects will be invited to participate in two visits within two years, the second being an optional visit. During each visit, subjects will undergo a PET/MRI after being injected with the study drug, Gallium-68 labeled PSMA-HBED-CC. This arm will be restricted to subjects who plan to undergo focal therapy. | Drug: Multiple PET/MRI with Gallium-68 labeled PSMA-HBED-CC<br>* Subjects have two visits (the second visit being optional) within two years. During each visit, they will undergo one PET/MRI with the study drug, Gallium-68 labeled PSMA-HBED-CC, a radiopharmaceutical<br>|
| Experimental: PET/CT<br>PET/CT with Gallium-68 labeled PSMA-HBED-CC: Subjects will have one visit during which they will undergo a PET/CT after being injected with the study drug, Gallium-68 labeled PSMA-HBED-CC. PET/CT occurs if a) an MRI can't be performed concurrently; or b) the participant already had an MRI of the abdomen/pelvis or pelvis only. | Drug: PET/CT with Gallium-68 labeled PSMA-HBED-CC<br>* Subjects have one visit, during which they will undergo one PET/CT with the study drug, Gallium-68 labeled PSMA-HBED-CC, a radiopharmaceutical<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Pathologic Lesions Detected by PSMA PET and PET/CT Compared to MP MRI | A scan was considered positive if the clinical interpretation was suspicious based on the clinical judgement of the reader. | At each visit, immediately after administration of the study drug, approximately 2-3 hours; with up to two visits within 2 years or less | 
| Number of Pathological Lesions Detected by PSMA PET/MRI and PET/CT Compared to MP MRI in Prostate Cancer Patients With Biochemical Recurrence by Anatomical Region Stratified by PSA Level | Patients were divided into subgroups based on their PSA levels and primary treatment modality. The primary treatment modality subgroups were post radical prostatectomy, post radiation therapy, and post radical prostatectomy and radiation therapy. 109 subjects out of 273 enrolled have data reported. Multiple patients sought care elsewhere and a small number of subjects had 2-year follow-up. This lead to a smaller analysis. | At each visit, immediately after administration of the study drug, approximately 2-3 hours; with up to two visits within 2 years or less | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Pathological Lesions Detected by PSMA PET/MRI and PET/CT Compared to MP MRI in Prostate Cancer Patients With Biochemical Recurrence by Anatomical Region | True positive rates for detecting lesions between PSMA PET/MRI and MP MRI in various anatomical locations were compared, including prostate/prostatic bed, N1 lymph nodes, N2 lymph nodes, and osseous lesions. Other anatomical sites are other than bone, node, and prostate. | At each visit, immediately after administration of the study drug, approximately 2-3 hours; with up to two visits within 2 years or less | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prostate cancer