Understanding resistance to PSMA-targeted radioligand therapy in prostate cancer

Mechanisms of Resistance to PSMA Radioligand Therapy: Radiation Resistance Versus Dose

This study is trying to understand why some men with prostate cancer don’t respond to a specific radiation therapy and how different factors might affect their treatment outcomes.

Quick facts

• Study type: Observational
• Enrollment: 125 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of California, San Francisco (Academic / other)
• Drugs / interventions: Radiation
• Locations: 3 sites (Los Angeles, California and 2 other locations)
• Trial ID: NCT05435495 on ClinicalTrials.gov

What this trial studies

This multicenter observational study aims to explore the mechanisms of resistance to Lutetium-based prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (177Lu-PSMA-RLT) in patients with prostate cancer. The study will assess the relationship between the absorbed radiation dose and treatment response, as well as the significance of the Post-Operative Radiation Therapy Outcomes Score (PORTOS) in predicting outcomes. Participants will undergo biopsies and blood draws before treatment, along with SPECT/CT imaging after the first and fourth treatment cycles to evaluate their response. Additionally, the study seeks to develop a novel signature of radiation sensitivity and understand the biological mechanisms behind treatment resistance.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older who are initiating treatment with Lutetium-based PSMA-targeted RLT and have accessible PSMA-avid lesions for biopsy.

Not a fit: Patients who do not have PSMA-avid lesions or are unable to undergo biopsy may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved treatment strategies for prostate cancer patients undergoing PSMA-targeted radioligand therapy.

How similar studies have performed: Other studies have explored PSMA-targeted therapies, but this specific approach to understanding resistance mechanisms is novel.

Eligibility criteria

Inclusion Criteria:

1. Initiating treatment with Lutetium based PSMA-targeted RLT.
2. Participants must have a PSMA-avid lesion that is accessible to biopsy. Biopsy of newly emerging radiographic metastases is desired and preferable to the biopsy of previously existing lesions whenever possible. Newly emerging lesions are defined as those that are absent on a previous scan, or those demonstrating unequivocal progression since initiation of the last treatment. Biopsies will be performed according to local institutional standards.
3. Patients on warfarin, aspirin, or other anti-coagulants are eligible provided they are deemed able to tolerate discontinuation of anti-coagulation for at least five days prior to the biopsy. Conversion to low molecular weight heparin prior to biopsy is permitted per local standard operating procedures, provided there is approval by the interventional radiologist or the PI.
4. Age \>=18 years.
5. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. Patients with significant congenital or acquired bleeding disorders (eg von Wildebrand's disease, acquired bleeding factor inhibitors).
2. Patients who are not able to undergo additional study related imaging procedures.

Where this trial is running

Los Angeles, California and 2 other locations

• University of California, Los Angeles — Los Angeles, California, United States (Recruiting)
• University of California, San Francisco — San Francisco, California, United States (Recruiting)
• Memorial Sloan Kettering — New York, New York, United States (Recruiting)

Study contacts

• Principal investigator: Thomas Hope, MD — University of California, San Francisco
• Study coordinator: Maya Aslam

Conditions Prostate Cancer; Radioligand Therapy