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Prostate CancerPhase 1LUTACTNCT07054346

Comparison of 177Lu-PSMA-617 and 225Ac-PSMA-617

A Phase 1 study testing 177 Lutetium Prostate-Specific Membrane Antigen 617, Actinium-225 Prostate-Specific Membrane Antigen 617 and Non-investigational, Prostatectomy in people with Prostate Cancer and Prostate Cancer (Diagnosis), run by Thomas Hope at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

There is evidence that Actinium-225 Prostate-Specific Membrane Antigen (225Ac-PSMA) has a potentially higher level of efficacy than 177 Lutetium Prostate-Specific Membrane Antigen (177Lu-PSMA) as a radioligand therapy. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
177 Lutetium Prostate-Specific Membrane Antigen 617, Actinium-225 Prostate-Specific Membrane Antigen 617 and Non-investigational, Prostatectomy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
1 siteUnited States
Study dates
8 Jul 2025to 30 Apr 2028
Phase
Phase 1
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
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥18 years.
  • Histologically confirmed prostate adenocarcinoma.
  • High-risk disease as defined as meeting 1 or more of the 3 following criteria:
  • Gleason score of 4+4 disease or higher, Or Gleason 4+3 with large cribriform component (defined as >0.25 mm in short diameter)
  • Pelvic nodal metastases on PSMA PET.
  • Extracapsular extension or seminal vesicle invasion on MRI or PSMA PET.
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  • No evidence of distant metastatic disease as determined by PSMA PET. Nodal disease at or below the iliac bifurcation (clinical stage N1) is allowed.
  • Maximum Standardized Uptake Value (SUVmax) in the primary tumor greater than 10 on PSMA PET using Gallium-68 (68Ga)-PSMA-11 or piflufolastat F 18 (18F-DCFPyL).
  • Note: this applies to treatment cohorts only; there are no SUV requirements for tissue-only cohorts (Control Group).
  • Target tumor in the prostate measuring greater than 1.0 cm on MRI.
  • Willing to undergo prostatectomy with or without lymph node dissection, and candidate for prostatectomy as determined by urologic oncology.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%),
  • Demonstrates adequate organ function as defined below:
  • Platelets ≥100,000/mcL, independent of transfusions or growth factors within 3 months of treatment start.
  • Hemoglobin ≥10 g/dL, independent of transfusions or growth factors within 3 months of treatment start.
  • Absolute Neutrophil Count (ANC) ≥1,500/microliter (mcL).
  • Creatinine clearance Glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m^2 , calculated using the Cockcroft-Gault equation.
  • Albumin ≥2.5 g/dL.
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3.0 x ULN.
  • Total bilirubin (TBIL) ≤2 x the institutional upper limit of normal (ULN). For participants with known Gilbert's Syndrome ≤3 x ULN is permitted.
  • Note: this applies to treatment cohorts only; there are no requirements for tissue-only cohorts (Control Group)
  • Ability to understand and the willingness to sign a written informed consent document.
  • Participants must provide consent to comply to recommended radioprotection precautions during study.
  • Participants must use adequate contraception and not donate sperm while on study drug and for at least 14 weeks after the last study treatment.

Who cannot join

  • Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. However, participants with a prior history of malignancy that has been adequately treated and who have been disease- free, treatment- free for more than 3 years prior to randomization, or participants with adequately treated non-melanoma skin cancer, superficial bladder cancer are eligible.
  • Individuals with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
  • Concurrent and serious (as determined by the principal investigator) medical conditions, including, but not limited to New York Heart Association class III or IV congestive heart failure, history of congenital prolonged QT syndrome, uncontrolled infection, known active hepatitis B or C or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation.
  • Has received prior prostate cancer therapy.
  • Prior 5-alpha reductase inhibitors (e.g. finasteride, dutasteride) allowed if discontinued at least 3 weeks prior to treatment start.
  • Has participated in a study of an investigational therapeutic product and received study treatment or used an investigational device within four weeks of the first dose of treatment.
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  • Prior external beam radiation therapy (EBRT) to the prostate or prostate bed.
  • Dry mouth that impacts the eating of food (i.e., requiring fluids prior to eating)
  • Additional exclusion criteria applicable only to participants undergoing intraarterial administration of PSMA RLT:
  • Severe allergy to iodinated contrast.
  • Severe atherosclerosis from prior CT imaging study, or greater than 10 pack-year smoking history if no prior imaging available.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Maya Aslam contact

(415) 514-8987

Maya.Aslam@ucsf.edu

United States1 site, 1 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

    Recruiting

Other trials in United States

About this study

Official title: Comparison of 177Lu-PSMA-617 and 225Ac-PSMA-617 in a Prostatectomy Model (LUTACT Trial)

There is evidence that Actinium-225 Prostate-Specific Membrane Antigen (225Ac-PSMA) has a potentially higher level of efficacy than 177 Lutetium Prostate-Specific Membrane Antigen (177Lu-PSMA) as a radioligand therapy. This single center, pilot study will compare differences in the mechanisms of actinium-225 and lutetium-177 radioligand therapies (RLT) in participants with high or very high risk localized or locoregional prostate cancer planning on undergoing a prostatectomy.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Compare the tumor absorbed dose between 177Lu-PSMA-617 and 225Ac-PSMA-617.
  2. Compare the immunologic priming of 177Lu-PSMA-617 and 225Ac-PSMA-617 with controls in prostatectomy specimens.

SECONDARY OBJECTIVES:

  1. Determine the safety and tolerability of neoadjuvant 177Lu-PSMA-617 and 225Ac-PSMA-617 in participants with high or very high-risk prostate cancer planning to undergo radical prostatectomy.
  2. Estimate PSA response for 177Lu-PSMA-617 and 225Ac-PSMA-617 treatment.
  3. Estimate the rate of pathologic response in participants treated with 177Lu-PSMA-617 and 225Ac-PSMA-617.

EXPLORATORY OBJECTIVES:

  1. Determine the relationship between percent cell necrosis and tumor absorbed dose for both 177Lu-PSMA-617 and 225Ac-PSMA-617.
  2. Compare the heterogeneity of cell necrosis for 177Lu-PSMA-617 and 225Ac-PSMA-617.
  3. Compare messenger ribonucleic acid (mRNA) expression profiles of tumor treated with 177Lu-PSMA-617, 225Ac-PSMA-617, and controls.
  4. Compare mRNA expression profiles of tumors in participants who achieve a PSA50 response and those that do not.
  5. Compare mRNA expression profiles of tumors from archival tissue and at time of prostatectomy.
  6. Compare the percent cell necrosis between participants receiving a single cycle of PSMA RLT versus participants receiving two cycles of PSMA RLT.
  7. Compare the change in uptake on PSMA Positron Emission Tomography (PET) to PSA response and percent cell necrosis.
  8. Descriptively evaluate cell necrosis at the tumor margins.
  9. Evaluate changes in peripheral immune activation markers following radioligand therapy.
  10. Compare the kidney absorbed dose (in Gray) between patients receiving 177Lu-PSMA-617 and those receiving 225Ac-PSMA-617, using post-treatment SPECT imaging acquired 7 days after administration of the first dose.
  11. Evaluate feasibility of PET for imaging actinium-225.

OUTLINE:

Participants will be assigned to 1 of 2 cohorts to receive 177Lu-PSMA-617 or 225Ac-PSMA-617. Additional participants undergoing prostatectomy without RLT will be enrolled as a control group. Participants enrolled in the RLT cohorts will receive 1 to 2 cycles of PSMA radioligand therapy up to 6 weeks apart before a scheduled, non-investigational, prostatectomy four weeks after PSMA radioligand therapy. Participants receiving RLT will be followed up for a safety assessment 6 weeks after surgery and for up to 60 months after prostatectomy for long term follow-up. Participants in the prostatectomy only cohort will have safety and long-term follow-up performed as part of clinical care up to 24 months after surgery.

Being tested
177 Lutetium Prostate-Specific Membrane Antigen 617, Actinium-225 Prostate-Specific Membrane Antigen 617, Non-investigational, Prostatectomy, Prostate Tissue Collection, Single-photon emission computed tomography (SPECT)/Computerized tomography (CT)
Keywords
Radioligand Therapy
Medical subject headings
Prostatic Neoplasms, Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 177 Lutetium Prostate-Specific Membrane Antigen 617Drug

    Also called 177Lu-PSMA-617, Pluvicto, lutetium Lu 177 vipivotide tetraxetan

    Given intravenously (IV) or intra-arterially (IA)

  • Actinium-225 Prostate-Specific Membrane Antigen 617Drug

    Also called 225Ac-PSMA-617, Radioligand 225Ac-PSMA-617

    Given IV or IA

  • Non-investigational, ProstatectomyProcedure or surgery

    Also called Prostatectomy

    Undergo non-investigational surgical procedure to remove prostate.

  • Prostate Tissue CollectionProcedure or surgery

    Also called Biospecimen Collection

    Whole prostate tissue will be collected for correlative research at time of prostatectomy.

  • Single-photon emission computed tomography (SPECT)/Computerized tomography (CT)Procedure or surgery

    Also called SPECT/CT

    Imaging procedure

  • Blood Sample CollectionProcedure or surgery

    Also called Blood Specimen

    Blood samples will be obtained for research purposes

Study groups in NCT07054346
Study groupRoleWhat they receive
Cohort 1 (177Lu-PSMA-617)ExperimentalFive participants will receive a single dose of 177Lu-PSMA-617 radioligand therapy intravenously (IV), five participants will receive a single dose of 177Lu-PSMA-617 intra-arterially (IA), and five participants will receive two doses over 6 weeks intravenously. In participants receiving two doses, the dose will be divided so that the cumulative dose will be equivalent to participants receiving a single dose. All participants will undergo prostatectomy four weeks after completing radioligand therapy and will be followed up 6 weeks after surgery for safety assessments and at 3, 6, 12, 36, 48, and 60 months for long-term outcomes.
Receives: Drug: 177 Lutetium Prostate-Specific Membrane Antigen 617; Procedure: Non-investigational, Prostatectomy; Procedure: Prostate Tissue Collection; Procedure: Single-photon emission computed tomography (SPECT)/Computerized tomography (CT); Procedure: Blood Sample Collection
Cohort 2 (225Ac-PSMA-617)ExperimentalFive participants will receive a single dose of 225Ac-PSMA-617 radioligand therapy IV, five participants will receive a single dose of 225Ac-PSMA-617 IA, and five participants will receive two doses over 6 weeks IV. In participants receiving two doses, the dose will be divided so that the cumulative dose will be equivalent to participants receiving a single dose. All participants will undergo prostatectomy four weeks after completing radioligand therapy and will be followed up 6 weeks after surgery for safety assessments and at 3, 6, 12, 36, 48, and 60 months for long-term outcomes.
Receives: Drug: Actinium-225 Prostate-Specific Membrane Antigen 617; Procedure: Non-investigational, Prostatectomy; Procedure: Prostate Tissue Collection; Procedure: Single-photon emission computed tomography (SPECT)/Computerized tomography (CT); Procedure: Blood Sample Collection
Control Group (Prostatectomy only)OtherParticipants will obtain a non-investigational prostatectomy. Tumor tissue obtained at the time of surgery will be utilized for comparisons with the cohorts receiving study therapies. All participants will undergo prostatectomy four weeks after completing radioligand therapy and will be followed up 6 weeks after surgery for safety assessments and up to 24 months after surgery.
Receives: Procedure: Non-investigational, Prostatectomy; Procedure: Prostate Tissue Collection; Procedure: Blood Sample Collection

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mean of tumor absorbed dose (Cohorts 1 and 2)

    The mean tumor absorbed dose on post-treatment SPECT imaging within 7 days of the first radioligand treatment (RLT) will be obtained by using MIM Software to measure absorbed dose and researchers will manually segment activity in the dominant prostate tumor while carefully excluding any activity within the bladder using a threshold of 5 Gray. Using this segmented volume, the mean dose within the tumor in Gray for each participant and standard deviation will be calculated and reported descriptively for Cohorts 1 and 2. A two-sample t-test comparing the dose between Cohort 1 and Cohort 2 and Analysis of Variance (ANOVA) model to compare the dose between different treatment/fractionation modalities within each cohort will be performed.

    Measured: 1 week

  2. Rate of Cluster of differentiation 3 positive (CD3+) T cell infiltration

    Immunohistochemistry will be performed using standard methods, and stained slides will be scanned using an automated microscope scanner. Five randomly selected fields (0.25 mm^2) from each participant's primary tumor will be captured. Using color-specific algorithms, CD3+ cell counts will be determined, and the mean of each of the five quantified fields will be used. We will use a two-sample t-test or ANOVA model comparing the CD3+ cell counts between Cohort 1 and Cohort 2 with participants who have not undergone prostatectomy enrolled in the biospecimen protocol, respectively.

    Measured: 1 day, at time of prostatectomy

Secondary outcomes (5)

  1. Proportion of participants with reported treatment-emergent adverse events (Cohorts 1 and 2)

    The proportion of participants with treatment-emergent adverse events, as classified by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5 (NCI CTCAE v5.0) will be reported for participants receiving RLT.

    Measured: Up to 6 weeks after last PSMA RLT administration

  2. Proportion of participants with perioperative complications

    The Clavien-Dindo classification is a widely used system for grading and classifying surgical complications. The Proportion of participants with documented perioperative complications following prostatectomy per the Clavien-Dindo classification will be reported.

    Measured: Up to 6 weeks after prostatectomy

  3. Median scores on the xerostomia-quality-of-life-scale (XeQoLS)

    The XeQoLS questionnaire measures the effects of salivary gland dysfunction and xerostomia on the four major domains of oral health-related quality of life: physical, pain, personal, and social. The questionnaire consists of 15 items, each rated on a 0-to-4 point Likert scale, with higher scores indicating more severe symptom burden. Median scores for each domain and global score and interquartile ranges will be reported.

    Measured: Up to 12 months after prostatectomy

  4. Proportion of participants with 50% decrease in level of prostate specific antigen (PSA50)

    The proportion of participants who achieve a greater than 50% decline from baseline PSA drawn prior to Cycle 1 Day 1 (C1D1), up to the day of prostatectomy, will be descriptively reported along with 95% binomial confidence interval. It will be compared between the two treatment Cohorts using a Fischer's test.

    Measured: Up to 8 weeks

  5. Proportion of participants with complete pathologic response

    Using the prostatectomy specimen, a board certified pathologies will determine pathologic complete response for each participant at time of prostatectomy. The pathologic response to the treatment in the prostate will be evaluated by percentage (0%, <10%, 10-25%, 50-75%, 75-100%) of viable tumor in the formalin-fixed paraffin embedded specimen. Complete pathologic response will be defined as no viable tumor (0%), and minimal residual disease will be defined as <10% of viable tumor. The number of participants in Cohorts 1 and 2 with complete pathologic response or minimal residual disease will be counted and the number of participants between the two cohorts will be compared using a Fisher's exact test. The proportion of complete pathologic response and minimal residual disease will be descriptively reported along with 95% binomial confidence interval.

    Measured: 1 day, at time of prostatectomy

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jul 2025
  2. Study start8 Jul 2025
  3. Primary completion30 Apr 2027 (estimated)
  4. Study completion30 Apr 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
45 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07054346
Sponsor's protocol ID
25922
Other IDs
NCI-2025-04497
Acronym
LUTACT
Status last verified
Aug 2026
First submitted
28 Jun 2025
Last updated
28 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: De-identified data may be shared with study collaborators during the course of the study.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 177 Lutetium Prostate-Specific Membrane Antigen 617, Actinium-225 Prostate-Specific Membrane Antigen 617 and Non-investigational, Prostatectomy in people with Prostate Cancer and Prostate Cancer (Diagnosis), run by Thomas Hope at 1 site 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 24 inclusion and 11 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 28 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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 of tumor absorbed dose (Cohorts 1 and 2) (time frame: 1 week). 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?

On the ClinicalTrials.gov record for NCT07054346.

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 28 Aug 2026.

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