Low-Count Quantitative SPECT for Men Treated With Radium-223

Overview

Internal radiotherapies (radiolabeled molecules that are systemically administered and localize to sites of disease) provide cancer-ablating doses to diseased cells while sparing adjacent normal tissues. \[223Ra\]RaCl2 (Xofigo) is the first FDA-approved alpha-particle emitting radiopharmaceutical therapy (αRPT), providing a survival benefit for men with bone metastatic castration-resistant prostate cancer. Systemically administered radiotherapies distribute throughout the patient, accumulating to unknown levels at sites of disease and in radiosensitive vital organs. The whole-body distribution means that absorbed doses in the patient extend far beyond a pre-defined treatment field. There is a lack of information about αRPT distribution and localization, and this confounds treatment monitoring, complicates dose and schedule personalization, and impedes drug development. Single-photon emission computed tomography (SPECT) imaging offers a mechanism to quantify uptake; however, αRPT administered activities are significantly lower than those used with diagnostic procedures, which presents a challenge for quantitation with conventional methods. Preliminary research shows that low-count quantitative SPECT (LC-QSPECT) imaging demonstrates reliable quantitation of regional uptake for αRPTs. The purpose of this study is to demonstrate the feasibility, tolerability and performance of LC-QSPECT imaging.

Interventions

• Device Low-count quantitative single-photon emission computed tomography imaging
  LC-QSPECT scans will be performed between 6 and 36 hours after administration of Xofigo during Cycles 1 and 3.

Primary outcome measures

• Spearman's correlation coefficient between the LC-QSPECT estimated uptake in the lesions and intestine with ex vivo activity sampling [Time frame: Through collection of ex vivo sample (estimated to be 3 months)]

Secondary outcome measures (12)

• LC-QSPECT related adverse events [Time frame: From start of LC-QSPECT imaging through 12 hours following LC-QSPECT imaging]
• Percentage of enrolled patients who withdraw from the study due to adverse events at least possibly related to LC-QSPECT (as chosen by patients or treating physician team) [Time frame: From start of LC-QSPECT imaging through 12 hours following LC-QSPECT imaging]
• Feasibility of conducting LC-QSPECT will be determined by percentage of SPECT scans that can be processed using the investigators' computational method [Time frame: Through completion of LC-QSPECT imaging (estimated to be 3 months)]
• Correlation between the LC-QSPECT measurements and PSA (Spearman Correlation Coefficient) [Time frame: Through completion of Xofigo treatment (estimated to be 6 months)]
• Correlation between the LC-QSPECT measurements and PSA doubling time (Spearman Correlation Coefficient) [Time frame: Through completion of Xofigo treatment (estimated to be 6 months)]
• Correlation between the LC-QSPECT measurements and bone-turnover markers (Spearman Correlation Coefficient) [Time frame: Through completion of Xofigo treatment (estimated to be 6 months)]
• Correlation between the LC-QSPECT measurements and Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire (Spearman Correlation Coefficient) [Time frame: Through completion of Xofigo treatment (estimated to be 6 months)]
• Correlation between the LC-QSPECT measurements and EuroQol-5 (EQ-5D-5L) questionnaire (Spearman Correlation Coefficient) [Time frame: Through completion of Xofigo treatment (estimated to be 6 months)]
• Correlation between the LC-QSPECT measurements and Brief Pain Inventory (BPI) questionnaire (Spearman Correlation Coefficient) [Time frame: Through completion of Xofigo treatment (estimated to be 6 months)]
• Correlation between the LC-QSPECT measurements and bone turnover (Spearman Correlation Coefficient) [Time frame: Through completion of Xofigo treatment (estimated to be 6 months)]
• Percentage of times that the use of the LC-QSPECT procedure resulted in any changes in treatment plans of the patients [Time frame: Through completion of Xofigo treatment (estimated to be 6 months)]
• Performance of the LC-QSPECT procedure using a no-gold-standard evaluation technique. [Time frame: Through completion of LC-QSPECT imaging (estimated to be 3 months)]

Eligibility criteria

Inclusion Criteria - Patients:

• Histologically or cytologically confirmed castration-resistant prostate cancer with symptomatic bone metastases.
• Minimum detectable skeletal lesion count of 3.
• Eligible to receive Xofigo.
• At least 18 years of age.
• ECOG performance status ≤ 3.
• Ability to understand and willingness to sign an IRB-approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.

Exclusion Criteria - Patients:

• Predominant visceral metastatic disease.
• Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial
• Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
• Concurrent alternative radiopharmaceuticals
• Inability to maintain stationary supine pose for 45-60 minutes

Eligibility Criteria - Physicians:

• Medical Oncologist or Radiation Oncologist at Siteman Cancer Center.
• Treating patients with prostate cancer.
• Willing to complete Physician Questionnaire during participation.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Diagnostic

Study locations

United States · 1 center

• Washington University School of Medicine — St Louis

Identifiers

NCT: NCT07221825 · 202506234 · R01EB031962

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗