Fluciclovine F18 or Ga68-PSMA PET/CT to Enhance Prostate Cancer Outcomes

Study Overview
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Brief Summary
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This phase II trial studies how well a positron emission tomography (PET)/computed tomography (CT) scan using fluciclovine F18 compared with a PET/CT scan with 68Ga-PSMA works in planning radiation treatments and enhancing outcomes in patients with prostate adenocarcinoma. Fluciclovine F18 and 68Ga-PSMA are types of tracers, called radiotracers, that are injected and can accumulate in tumor cells to develop images of them during a PET/CT scan. It is not yet known whether giving fluciclovine F18 or 68Ga-PSMA may work better in planning radiation treatments and enhancing outcomes in patients with prostate adenocarcinoma.

Detailed Description
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PRIMARY OBJECTIVES I. Improve the outcomes of post-prostatectomy radiotherapy prostate cancer patients via selection and treatment optimization with advanced molecular imaging with dose escalation. II. Establish the role of advanced molecular imaging with fluciclovine F18 (fluciclovine [18F]) and gallium Ga68-labeled prostate specific membrane antigen PSMA-11 (68Ga-PSMA) PET/CT in influencing post-prostatectomy radiotherapy decision-making. III. Establish the role of advanced molecular imaging with fluciclovine 18F or 68Ga-PSMA in altering radiotherapy treatment volumes. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive fluciclovine F18 intravenously (IV) and undergo a PET/CT over approximately 30 minutes. ARM II: Patients receive 68Ga-PSMA IV, wait 60 minutes, then undergo a PET/CT over approximately 30 minutes. After completion of study treatment, patients are followed up every 6 months for up to 5 years.

Official Title
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Advanced PET-CT Directed Post-Prostatectomy Radiotherapy to Enhance Prostate Cancer Outcomes

Conditions
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Prostate Adenocarcinoma

Intervention / Treatment
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* Procedure: Computed Tomography
* Drug: Fluciclovine F18
* Radiation: Gallium Ga68-labeled PSMA-11
* Procedure: Positron Emission Tomography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adenocarcinoma of the prostate, post radical-prostatectomy Detectable prostate-specific antigen (PSA) Eastern Cooperative Oncology Group (ECOG)/Zubrod performance status of 0-2 No definitive findings for skeletal metastasis on technetium 99-m methyl diphosphonate (MDP) or F-18 PET bone scan No definitive findings of systemic (extrapelvic) metastasis on CT and/or magnetic resonance (MR) scan of abdomen and pelvis Willingness to undergo pelvic radiotherapy Exclusion Criteria: Contraindications to radiotherapy (including active inflammatory bowel disease or prior pelvic radiotherapy) Inability to undergo fluciclovine or Ga-PSMA PET-CT Definitive findings of systemic metastasis on conventional imaging or biopsy Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years Severe acute co-morbidity, defined as follows: Unstable angina and/or congestive heart failure requiring hospitalization in the last 3 months Transmural myocardial infarction within the last 6 months Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration Acquired immune deficiency syndrome (AIDS) based upon current Center for Disease Control (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immunocompromised patients

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (fluciclovine F18, PET/CT)<br>Patients receive fluciclovine F18 IV and undergo positron emission tomography (PET)/computed tomography (CT) over 30 minutes. | Procedure: Computed Tomography<br>* Undergo PET/CT<br>* Other names: CAT scan;Drug: Fluciclovine F18<br>* Given IV<br>* Other names: Axumin;Procedure: Positron Emission Tomography<br>* Undergo PET/CT<br>* Other names: Proton magnetic resonance spectroscopic imaging;|
| Active Comparator: Arm II (68Ga-PSMA, PET/CT)<br>Patients receive gallium Ga68-labeled PSMA-11 IV, wait 60 minutes, then undergo positron emission tomography (PET)/computed tomography (CT) over 30 minutes. | Procedure: Computed Tomography<br>* Undergo PET/CT<br>* Other names: CAT scan;Radiation: Gallium Ga68-labeled PSMA-11<br>* Given IV<br>* Other names: 68Ga-PSMA-HBED-CC;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 |
| --- | --- | --- |
| Disease-free survival | A survival analysis will be conducted on disease-free survival (DFS). The survivor functions for DFS will be estimated with Kaplan and Meier method and plotted. The logrank test will be used to test the difference in DFS of (a) both arms in aggregate with the survivor function on our prior R01 trial and (b) between the two study arms. | Up to 2 years after study start | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decision to offer radiotherapy | Decision to offer radiotherapy or not between the initial (pre-fluciclovine F18 or 68Ga-PSMA) and final (post-fluciclovine F18 or 68Ga-PSMA) treatment decisions will be compared using the Clopper-Pearson (exact) binomial test. | Up to 5 years after study start | 
| Decision to treat pelvic nodes | Decision to provide treatment on pelvic nodes or not between the initial (pre-fluciclovine F18 or 68Ga-PSMA) and final (post-fluciclovine F18 or 68Ga-PSMA) treatment decisions will be compared using the Clopper-Pearson (exact) binomial test. | Up to 5 years after study start | 
| Decision to boost between the initial and final treatment decisions | Decision to boost or not between the initial (pre-fluciclovine F18 or 68Ga-PSMA) and final (post-fluciclovine F18 or 68Ga-PSMA) treatment decisions will be compared using the Clopper-Pearson (exact) binomial test. | Up to 5 years after study start | 
| Prostate bed clinical target volume (CTV) and planning target volume (PTV) | Paired t-test will be used to compare the target volumes (CTV and PTV) and the planned dose delivered to surrounding bladder, rectum, and penile bulb between the initial (pre-positron emission tomography [PET]) and final (post-PET) radiation treatment plans. | Up to 5 years after study start | 
| PTV of the rectum (V65, V40) | Spearman's correlation coefficient will be used to measure the correlations of the bladder and rectum dosimetric endpoints (V65, V40) with the grades (0, 1, 2, or 3) of acute genitourinary (GU) or gastrointestinal (GI) toxicity. A Wald test will be used to test the significance level of their correlations. A Cox model will be employed to assess the relationship between the time to late GU or GI toxicity (grade ≥ 2) and the bladder and rectum dosimetric endpoints (V65, V40), respectively. | Up to 5 years after study start | 
| PTV of the bladder (V65, V40) | Spearman's correlation coefficient will be used to measure the correlations of the bladder and rectum dosimetric endpoints (V65, V40) with the grades (0, 1, 2, or 3) of acute GU or GI toxicity. A Wald test will be used to test the significance level of their correlations. A Cox model will be employed to assess the relationship between the time to late GU or GI toxicity (grade ≥ 2) and the bladder and rectum dosimetric endpoints (V65, V40), respectively. | Up to 5 years after study start |