Mechanisms of Resistance to PSMA Radioligand Therapy

NCT05435495 | Recruiting

• 2 other identifiers: 19553R01CA235741-03
• Study Type: observational
• Target: 125
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Prostate Cancer

Keywords

Radioligand Therapy

Outcome Measures

Primary Outcomes (2)

• 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).

  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.

  Up to 6 months

Study Arms (1)

Participants undergoing 177Lu-PSMA-617 treatment

Participants undergoing PSMA targeted radioligand therapy with at least four cycles of treatment planned will undergo the following: SPECT/CTs will be performed 24 hours after the first treatment and after the fourth treatment, a tumor biopsy will be performed prior to the first 177Lu-PSMA radioligand therapy, a blood will be drawn prior to treatment for future research, and an optional tumor biopsy and blood draw for future research, may also be obtained at time of progression.

Procedure: Single-photon emission computed tomography; Procedure: Blood Draw; Procedure: Tumor Biopsy

Interventions

Single-photon emission computed tomography PROCEDURE

Imaging procedure

Also known as: SPECT/CT

Participants undergoing 177Lu-PSMA-617 treatment

Blood Draw PROCEDURE

Blood draw for future research tests (45-60 mL).

Participants undergoing 177Lu-PSMA-617 treatment

Tumor Biopsy PROCEDURE

Guided biopsy of lesion

Also known as: Biopsy

Participants undergoing 177Lu-PSMA-617 treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Participants will be selected from patients enrolled on Lutetium based PSMA-RLTs and expected to receiving at least four cycles of PSMA-RLT

You may qualify if:

• Initiating treatment with Lutetium based PSMA-targeted RLT.
• 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.
• 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.
• Age \>=18 years.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

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

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Cancer Institute (NCI): collaborator
• Prostate Cancer Foundation: collaborator

Study Sites (3)

University of California, Los Angeles

Los Angeles, California, 90095, United States

RECRUITING

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

Memorial Sloan Kettering

New York, New York, 10065, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Tissue and blood samples will be obtained.

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Blood Specimen Collection; Biopsy

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical

Study Officials

• Thomas Hope, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maya Aslam

CONTACT

(415) 514-8987; Maya.Aslam@ucsf.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2022
• First Posted: June 28, 2022
• Study Start: October 21, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)