This phase II trial compares the effect of FDG-positron emission tomography (PET)-guided metastasis directed radiation therapy (MDRT) in combination with standard treatments to standard treatments alone in treating patients with prostate cancer that is sensitive to androgen-deprivation therapy (ADT) and has spread from where it first started (primary site) to other places in the body (metastatic). Prostate cancer is the second leading cause of cancer death among men in the United States, despite the approval of several life-prolonging treatments by the Food and Drug Administration. However, over the past 10 years, there have been significant improvements in prolonging the lives of those with metastatic hormone sensitive prostate cancer, specifically by adding treatments to standard therapy, such as ADT. More recently, trials have demonstrated a benefit of using radiotherapy (high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors) to delay the progression of cancer and prolong life for patients with metastatic disease. Imaging scans with FDG-PET may be able to identify cancer sites that remain active despite standard treatment. Giving MDRT plus standard treatment to patients with FDG-PET-identified cancer sites may work better than standard treatment alone in treating metastatic hormone sensitive prostate cancer.
Patients must have metastatic prostate cancer on conventional imaging (CT scan, MRI, and/or bone scan).
Note; Patients who had metastatic disease on conventional imaging prior to beginning ADT, but which has now resolved, are still eligible if they meet remaining eligibility criteria
Patients must be ≥ 18 years of age at the time of informed consent.
Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-3.
Patients with prostate cancer that is castration resistant, which is defined as two consecutive rising PSA values despite testosterone level < 50 ng/dL.
Patients who started androgen deprivation therapy (ADT) more than 26 weeks +/- 26 weeks (1 year) prior to enrollment.
Note: ADT is defined as luteinizing hormone-releasing hormone (LHRH) agonist (e.g. leuprolide, goserelin) or antagonist (e.g. degarelix, relugolix) or surgical castration. Bicalutamide 50 mg daily does not count as ADT.
Note: Patients will not be excluded if they were previously on intermittent therapy, as long as the current "on" period started within one year of enrollment.
Parallel
Antiandrogen Therapy
DrugUndergo SOC ADT
Bone Scan
Procedure/SurgeryUndergo bone scan
Computed Tomography
Procedure/SurgeryUndergo CT
Cytotoxic Chemotherapy
DrugReceive SOC cytotoxic chemotherapy
FDG-Positron Emission Tomography
Procedure/SurgeryUndergo FDG-PET
Radiation Therapy
RadiationUndergo MDRT
6
Treatment groupsSee each treatment group below.
Progression free survival (PFS) (Cohort 1)
Will be estimated using the method of Kaplan-Meier and compared between treatment arms (Arms 1A and 1B) using the log-rank test. PFS rate at 18 months following randomization will be estimated and reported with the corresponding confidence intervals.
Complete response rate (Cohort 2)
Will be estimated as the proportion of patients who demonstrate response based on fludeoxyglucose F-18-positron emission tomography (FDG-PET)-2 as compared to baseline (FDG-PET-1), and will be reported with the corresponding Clopper-Pearson confidence intervals. Response rates will be compared between Arms 2A and 2B using Fisher's exact test.
Radiographic PFS (rPFS) (Cohort 1)
Will be estimated using the method of Kaplan-Meier and compared between treatment arms (Arms 1A and 1B) using the log-rank test. rPFS rate at 18 months following randomization will be estimated and reported with the corresponding confidence intervals.
Proportions of patients with metastatic hormone sensitive prostate cancer (mHSPC) who achieve a serum PSA level < 0.4 ng/mL and < 0.01 ng/mL (Cohort 1)
Will be compared using the Fisher's exact test, and estimates by arm will be reported with the corresponding Clopper-Pearson confidence intervals.
Proportion of patients with Skeletal Related Events (SRE) (Cohort 1)
Will be compared using the Fisher's exact test, and estimates by arm will be reported with the corresponding Clopper-Pearson confidence intervals.
Incidence of adverse events (AEs) of metastasis directed radiation therapy (MDRT) (Cohort 1)
Will be summarized by arm using the Common Terminology Criteria in Adverse Events (CTCAE) version (v) 5.0 system organ class and term. For each subject, highest AE grade across multiple occurrences of the same event will be recorded, and the number of patients will be summarized by AE type and grade.
Click on the lead sponsor to view all of their trials.
Northwestern University
Lead sponsor
National Cancer Institute (NCI)
Collaborator
