The purpose of this study is to look for markers of how Ra-223 improves the lives of men with prostate cancer. This study makes use of Ra-223 in the standard FDA-approved way, but adds non-standard testing in an attempt to gain insight about how the drug works and how best to track patients who are receiving the drug.
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied. This research study is designed to examine a treatment strategy that is standard but still relatively new. Ra-223 consists of a series of six infusions given once every 4 weeks. It was FDA approved in 2013 for the treatment of prostate cancer that has spread to bone and has grown despite ADT ("hormonal therapy"). Ra-223 was approved because it was shown to improve the length of the lives of the men with prostate cancer who received it. Despite that important benefit, it is not known to improve other standard markers of prostate cancer such as PSA blood tests (a blood marker that is used to track cancer activity in men who have prostate cancer) and standard imaging scans such as bone scans and computed tomography (CT) scans. If participants and their doctors do not have good markers of whether or not the cancer is responding to therapy, it is harder to make decisions about whether to continue that therapy. This is a current problem. This study makes use of Ra-223 in the standard FDA-approved way, but adds non-standard testing in an attempt to gain insight about how the drug works and how best to track patients who are receiving the drug.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
22
Blood will be drawn for standard and nonstandard testing on day one, day 4, and weeks 5, 9, 13, 17, 21, 25, 37, and 93.
Standard CT scans will be carried out prior to treatment, week 9, and week 25.
Approximately half of the study patients (n=10) will undergo experimental FACBC PET/MRI testing at 2 time points each: (1) prior to therapy, and (2) week 9.
Massachusetts General Hospital
Boston, Massachusetts, United States
Bone Scan Index
Automated bone scan index (aBSI) is an imaging prognostic biomarker used to quantitatively assess effect of therapy. aBSI expresses the tumor burden in bone as a percent of the total skeletal mass. An aBSI value of 1.0 indicates the tumor(s) to be present in 1% of the entire skeleton (arms and legs included).
Time frame: Baseline to 2 Months
Percentage of Skeletal Mass Occupied by a Lesion, Stratified by 18 Month Survival Status
Mean change in automated bone scan index (aBSI) at 2 months (i.e. approximately week 9) as assessed by aBSI will be described by 18 month survival status. In other words, decline in aBSI at 2 months on therapy will be evaluated as a predictive biomarker of survival at 18 months.
Time frame: Baseline and 2 months
Circulating Tumor Cell (CTC) Number
The presence of circulating tumor cells (CTCs) in the peripheral blood, will be assessed by by the FDA-approved assay CELLSEARCH® CTC Test, is associated with decreased progression-free survival and decreased overall survival in patients treated for metastatic prostate cancer.
Time frame: Baseline/Day 1, Day 30, Day 60
Circulating Biomarkers of the Tumor Microenvironment
Bone turnover markers (i.e., serum bone specific alkaline phosphatase and N-telopeptide) and plasma biomarkers of inflammation and angiogenesis will be assessed serially. Our analyses of circulating biomarkers of the tumor microenvironment were more limited than originally planned due to a freezer malfunction that compromised our frozen samples that had been saved for later batched analyses. The reported values within the table below reflect CTCm score which is a previously described analysis that uses droplet digital PCR to assess gene expression from circulating tumor cells (CTCs) isolated using the microfluidic CTC-iChip. CTCm score, by published convention, does not have units and does not have a normal range. In the present study, the normalized CTCm score was calculated as described previously using weighting coefficients. It is considered better to have a lower CTCm score. The table contains \[mean (standard deviation)\] of CTCm score for each group at the specified timepo
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 at a dose of 50 kBq/kg body weight by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments.
Standard bone scans will be carried out prior to treatment, week 9, and week 25.
Time frame: Baseline/Day 1, Day 30, Day 60
Baseline Pain Score Evaluation as a Predictor of Survival
Pain and narcotic analgesic use was assessed by the 4-item Brief Pain Inventory (BPI). This instrument contains 4 items, with each item reported on a scale of 0-10, meaning that total possible range is 0-40. For each question's 0-10 response scale, 0 meant no pain/interference and 10 meant worst pain imaginable/complete interference. Overall survival (OS) was defined as the interval between the start of therapy and the date of death or censor. For the analysis presented in the table, the algorithm of Contal-O'Quigley was applied to the data using leave-one-out jack-knife resampling to determine the optimal division points according to pain score on 4-item BPI at baseline. Each iteration of the algorithm produced an estimate of the "best" division point based on the data. With this method, optimal cut-point for this cohort was baseline total BPI score \< 8 vs ≥8. Median survival for each sub-group is reported as months (with range in parentheses).
Time frame: Baseline through study completion, up to approximately 5 years
Baseline Global Health Score Evaluation as a Predictor of Survival
Baseline Global Health Score was reported by participants on a scale of 0 ("The worst health you can imagine") to 100 ("The best health you can imagine"). Overall survival (OS) was defined as the interval between the start of therapy and the date of death or censor, expressed here in months. For the analysis presented in the table, the algorithm of Contal-O'Quigley was applied to the data using leave-one-out jack- knife resampling to determine the optimal division points according to Global Health Score at baseline. Each iteration of the algorithm produced an estimate of the "best" division point based on the data. With this method, optimal cut-point for this cohort was baseline Global Health Score ≥95 or \<95. Median survival for each sub-group is reported as months (with range in parentheses).
Time frame: Baseline through study completion, up to approximately 5 years.