Prostate CancerNCT05435495
Mechanisms of Resistance to PSMA Radioligand Therapy
An observational study of Prostate Cancer, run by University of California, San Francisco at 3 sites in United States.
Trial summary
This is a multicenter, correlative study to existing Lutetium based prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) trials and uses. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Single-photon emission computed tomography, Blood Draw and Tumor Biopsy
- Type of treatment
- Surgery or procedure
- How many people
- 125 participants
- Where
- 3 sitesUnited States
- Study dates
- 21 Oct 2021to 31 Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites, 3 recruiting
- Recruiting
University of California, Los Angeles
Los Angeles, California, 90095
Johannes Czernin, MD
Matthew Rettig, MD
- Recruiting
Memorial Sloan Kettering
New York, New York, 10065
Lisa Bodei, MD
Michael Morris, MD
- Recruiting
University of California, San Francisco
San Francisco, California, 94143
Maya Aslam, 415-514-8987, Maya.Aslam@ucsf.edu
877-827-3222, cancertrials@ucsf.edu
About this study
Official title: Mechanisms of Resistance to PSMA Radioligand Therapy: Radiation Resistance Versus Dose
This is a multicenter, correlative study to existing Lutetium based prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) trials and uses.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- Conditions
- Prostate Cancer
- Being tested
- Single-photon emission computed tomography, Blood Draw, Tumor Biopsy
- Keywords
- Radioligand Therapy
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Single-photon emission computed tomographyProcedure or surgery
Also called SPECT/CT
Imaging procedure
Blood DrawProcedure or surgery
Blood draw for future research tests (45-60 mL).
Tumor BiopsyProcedure or surgery
Also called Biopsy
Guided biopsy of lesion
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: Single-photon emission computed tomography; Procedure: Blood Draw; Procedure: Tumor Biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: Up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2022
- Study start21 Oct 2021
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 125 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Prostate Cancer Foundation
- Responsible party
- Sponsor
- Investigators
- Thomas Hope, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05435495
- Sponsor's protocol ID
- 19553
- Other IDs
- R01CA235741-03
- Status last verified
- Mar 2026
- First submitted
- 22 Jun 2022
- Last updated
- 18 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Resistance to PSMA Radioligand Therapy: Radiation Resistance Versus Dose
- ClinicalTrials.gov ID
- NCT05435495
- Acronym / sponsor ID
- 19553
- Conditions
- Prostate Cancer
- Keywords
- Radioligand Therapy
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 125 participants (estimated)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Prostate Cancer Foundation
- Study start
- 21 Oct 2021 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 28 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Participants undergoing 177Lu-PSMA-617 treatment | – | Procedure: Single-photon emission computed tomography, Procedure: Blood Draw, Procedure: Tumor BiopsyParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Single-photon emission computed tomographyAlso: SPECT/CTImaging procedure | Procedure or surgery | Participants undergoing 177Lu-PSMA-617 treatment |
| Blood DrawBlood draw for future research tests (45-60 mL). | Procedure or surgery | Participants undergoing 177Lu-PSMA-617 treatment |
| Tumor BiopsyAlso: BiopsyGuided biopsy of lesion | Procedure or surgery | Participants undergoing 177Lu-PSMA-617 treatment |
Primary outcome
Mean whole body tumor absorbed dose (WB Dose) across all metastatic lesions
Time frame: Up to 6 months
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).
Median PORTOS score
Time frame: Up to 6 months
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Thomas Hope, MD principal investigator
University of California, San Francisco
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Prostate Cancer, run by University of California, San Francisco at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Maya Aslam ((415) 514-8987, Maya.Aslam@ucsf.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean whole body tumor absorbed dose (WB Dose) across all metastatic lesions (time frame: Up to 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2026.