Metastatic Castration-resistant Prostate Cancer
Conditions
Keywords
FLT PET, CSE-MRI, active bone marrow, mCRPC
Brief summary
This study compares two different imaging procedures to each other, one using positron emission tomography (PET) with fluorothymidine F-18 (FLT) (FLT PET for short), and the other using chemical shift-encoded (CSE) magnetic resonance imaging (MRI) or CSE-MRI for short, to determine specifically if CSE-MRI is as accurate as FLT PET in telling the difference between active and inactive marrow. The best way to do the comparison between the two imaging procedures is if they are done at the same time on the same patient. This is possible with use of a scanner at the University of Wisconsin Hospitals and Clinics (UW Health), the GE SIGNA PET/MR scanner. The prediction is that CSE-MRI as accurate as FLT at telling the difference between active and inactive marrow in patients with metastatic prostate cancer, and that is the primary reason for this study. 15 participants will be enrolled and on study for up to 14 months.
Detailed description
This single-site, single-arm study will evaluate the accuracy of active bone marrow (ABM) segmentation with CSE-MRI by comparing to the established technique of FLT PET in patients with PSMA+ mCRPC who are scheduled to receive Lutetium-177 Prostate-Specific Membrane Antigen (177Lu-PSMA) (PLUVICTO®) Radiopharmaceutical Therapy (RPT) as standard of care. All standard of care testing, monitoring, and administration for 177Lu-PSMA RPT (PLUVICTO®) will be followed for this study. Participants will receive 177Lu-PSMA RPT (PLUVICTO®) for a total of 6 doses, or until disease progression or unacceptable toxicity. Doses of 177Lu-PSMA RPT will be given at least 6 weeks apart. At the discretion of the prescribing physician, standard of care PSMA PET/MRI will be performed at any time during cycles 2-4, and also within 6 months of the final administration of 177Lu-PSMA RPT; during these scans, the CSE-MRI will also be acquired. Participants will be followed for 6 months following the final administration of 177Lu-PSMA RPT. The primary endpoint is a calculation of the mean Dice similarity coefficient (DSC) between active bone marrow volumes derived from CSE-MRI and ¹⁸F-FLT PET across all enrolled patients. A mean DSC of ≥0.7 will indicate that CSE-MRI is a clinically acceptable alternative to FLT PET for identifying ABM. With the exception of the research-related CSE-MRI and FLT PET scans, all assessments, laboratory tests, RPT, and imaging scans are standard of care.
Interventions
DRUG3'-Deoxy-3'-[18F]-fluorothymidine
Within 29 days prior to 177Lu-PSMA RPT, participants will undergo 18F-FLT PET to assess proliferating bone marrow and CSE-MRI to generate a fat fraction map on a GE SIGNA PET/MR scanner. This is expected to last 2-3 hours. FLT injections will be administered one hour before imaging for tracer uptake. Participants will receive an IV injection of up to 10 mCi (370 MBq) of 18F-FLT. The patient will receive 1 CSE-MRI/FLT PET scan prior to the start of therapy.
DEVICEChemical-shift-encoded MRI
Within 29 days prior to 177Lu-PSMA RPT, participants will undergo 18F-FLT PET to assess proliferating bone marrow and CSE-MRI to generate a fat fraction map on a GE SIGNA PET/MR scanner. This is expected to last 2-3 hours. The patient will receive 1 CSE-MRI/FLT PET scan prior to the start of therapy. Up to 3 CSE-MRI scans will be completed as part of this study. At the physician's discretion, a single standard of care (SOC) mid-treatment PSMA PET/MRI can be performed any time during cycles 2-4, and a SOC post-treatment can be done within 6 months of final treatment. CSE-MRI will be acquired during these scans.
Sponsors
University of Wisconsin, Madison
GE Healthcare
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ability to understand and the willingness to sign a written informed consent document. * Patients must be informed of the experimental nature of the study and its potential risks, and must sign institutional review board (IRB) approved consent form indicating such understanding. * Individuals at least 18 years of age. * Patients must have histologically or cytologically confirmed prostate cancer. * Patients must be clinically deemed appropriate for standard of care Lu-177 PSMA RPT. * Eastern Cooperative Oncology Group (ECOG) performance 0-2 * Patients must be able to comply with all study procedures, including having both the ability and willingness to lie flat for ≥ 30 minutes during imaging.
Exclusion criteria
* Patients receiving any concurrent therapy known to impact bone marrow (either stimulate or suppress the marrow, for example G-CSF). * Patients treated with chemotherapy or 223Ra radiotherapy within 4 weeks. * All acute toxic effects of any prior therapy (including surgery, radiation therapy, chemotherapy) must have resolved to a grade ≤ 2 according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5 (CTCAE). * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements per treating physician discretion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Dice similarity coefficient (DSC) | up to 14 months | The mean Dice similarity coefficient (DSC) between active bone marrow volumes derived from CSE-MRI and ¹⁸F-FLT PET across all enrolled patients. A mean DSC of ≥0.7 will indicate that CSE-MRI is a clinically acceptable alternative to FLT PET for identifying ABM |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Mean Tumor Absorbed Dose (Gy) | up to 14 months | Difference in mean tumor absorbed dose (Gy) across three lesion-segmentation methods, with segmentation performance characterized by DSC relative to physician manual contours. |
| Variance in Tumor and Bone Marrow Volume | up to 14 months | Repeatability will be measured by variance in tumor and bone marrow volumes. |
| Variance in Tumor and Bone Marrow Doses | up to 14 months | Repeatability will be measured by variance in tumor and bone marrow doses |
| Difference in Mean Absorbed Dose (Gy) | up to 14 months | Difference in mean absorbed dose (Gy) between conventional and CSE-MRI-based ABM dosimetry methods |
Countries
United States
Contacts
CONTACTCancer Connect
PRINCIPAL_INVESTIGATORMichael Lawless, PhD
UW School of Medicine and Public Health
Outcome results
None listed