RecruitingObservational

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

NCT ID: NCT05435495Sponsor: University of California, San FranciscoLast updated: 2026-03-18

Summary

This is a multicenter, correlative study to existing Lutetium based prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) trials and uses.

Detailed description

PRIMARY OBJECTIVES: I. To determine the relationship between whole body tumor absorbed dose and response Lutetium based prostate-specific membrane antigen-targeted radioligand therapy (177Lu-PSMA-RLT). II. To determine the relationship between Post-Operative Radiation Therapy Outcomes Score (PORTOS) score and response to 177Lu-PSMA-RLT. III. To determine the relative importance of radiation dose (whole body tumor absorbed dose) and radiation sensitivity (PORTOS score) as a marker of response to 177Lu-PSMA-RLT. EXPLORATORY OBJECTIVES: I. To develop novel signature of radiation sensitivity. II. To evaluate tumor biopsies to understand mechanisms of resistance. III. To understand utility of post-cycle 4 single-photon emission computed tomography (SPECT/CT) to evaluate treatment response. Study participants will undergo a biopsy and blood draw prior to the initiation of planned therapy, as well as SPECT/CT imaging performed after the first and fourth treatments. One SPECT/CT scan will be performed 24 (+/- 6) after the first treatment, and after the fourth treatment, a 24 +/- 6-hour post-treatment SPECT/CT will be performed. Additionally, study participants may choose to undergo optional biopsy and blood draw at time of progression.

Arms & interventions

ProcedureSingle-photon emission computed tomography
Imaging procedure
ProcedureBlood Draw
Blood draw for future research tests (45-60 mL).
ProcedureTumor Biopsy
Guided biopsy of lesion

Outcome measures

Primary

Mean whole body tumor absorbed dose (WB Dose) across all metastatic lesions
The unit density sphere model will be implemented using OLINDA, a second-generation personal computer software for internal dose assessment in nuclear medicine to measure mean dose across all metastatic lesions. This approach uses the three time-point SPECT/CTs to create a whole-body dose map, which can then be segmented. Using OLINDA, the total dose to each tumor will be calculated as the integral of activity over time estimated out to 500 hours. Dose will be calculated in gray (Gy).
Time frame: Up to 6 months
Median PORTOS score
PORTOS is a gene signature that predicts salvage radiation success. A PORTOS score of zero (called a "low" PORTOS) means it predicts no benefit from salvage radiotherapy. A PORTOS greater than zero (called a "high" PORTOS score) predicts a benefit from salvage radiation.
Time frame: Up to 6 months

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

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.

Study locations (3)

University of California, Los Angeles

Los Angeles, California, 90095

Recruiting

Johannes Czernin, MD · Principal Investigator

Matthew Rettig, MD · Principal Investigator

University of California, San Francisco

San Francisco, California, 94143

Recruiting

Maya Aslam · Contact

415-514-8987 Maya.Aslam@ucsf.edu

· Contact

877-827-3222 cancertrials@ucsf.edu

Thomas Hope, MD · Principal Investigator

Memorial Sloan Kettering

New York, New York, 10065

Recruiting

Lisa Bodei, MD · Principal Investigator

Michael Morris, MD · Principal Investigator