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

NCT ID: NCT07054346

Last Updated: 2025-12-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

45 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-07-08

Study Completion Date

2028-04-30

Brief Summary

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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.

Detailed Description

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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.

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.

Conditions

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Prostate Cancer Prostate Cancer (Diagnosis) High-risk Prostate Cancer Localized Prostate Carcinoma Very High Risk Prostate Carcinoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort 1 (177Lu-PSMA-617)

Five 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, and 60 months for long-term outcomes.

Group Type EXPERIMENTAL

177 Lutetium Prostate-Specific Membrane Antigen 617

Intervention Type DRUG

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

Non-investigational, Prostatectomy

Intervention Type PROCEDURE

Undergo non-investigational surgical procedure to remove prostate.

Prostate Tissue Collection

Intervention Type PROCEDURE

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

Single-photon emission computed tomography (SPECT)/Computerized tomography (CT)

Intervention Type PROCEDURE

Imaging procedure

Blood Sample Collection

Intervention Type PROCEDURE

Blood samples will be obtained for research purposes

Cohort 2 (225Ac-PSMA-617)

Five 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, and 60 months for long-term outcomes.

Group Type EXPERIMENTAL

Actinium-225 Prostate-Specific Membrane Antigen 617

Intervention Type DRUG

Given IV or IA

Non-investigational, Prostatectomy

Intervention Type PROCEDURE

Undergo non-investigational surgical procedure to remove prostate.

Prostate Tissue Collection

Intervention Type PROCEDURE

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

Single-photon emission computed tomography (SPECT)/Computerized tomography (CT)

Intervention Type PROCEDURE

Imaging procedure

Blood Sample Collection

Intervention Type PROCEDURE

Blood samples will be obtained for research purposes

Control Group (Prostatectomy only)

Participants 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.

Group Type OTHER

Non-investigational, Prostatectomy

Intervention Type PROCEDURE

Undergo non-investigational surgical procedure to remove prostate.

Prostate Tissue Collection

Intervention Type PROCEDURE

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

Blood Sample Collection

Intervention Type PROCEDURE

Blood samples will be obtained for research purposes

Interventions

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177 Lutetium Prostate-Specific Membrane Antigen 617

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

Intervention Type DRUG

Actinium-225 Prostate-Specific Membrane Antigen 617

Given IV or IA

Intervention Type DRUG

Non-investigational, Prostatectomy

Undergo non-investigational surgical procedure to remove prostate.

Intervention Type PROCEDURE

Prostate Tissue Collection

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

Intervention Type PROCEDURE

Single-photon emission computed tomography (SPECT)/Computerized tomography (CT)

Imaging procedure

Intervention Type PROCEDURE

Blood Sample Collection

Blood samples will be obtained for research purposes

Intervention Type PROCEDURE

Other Intervention Names

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177Lu-PSMA-617 Pluvicto lutetium Lu 177 vipivotide tetraxetan 225Ac-PSMA-617 Radioligand 225Ac-PSMA-617 Prostatectomy Biospecimen Collection SPECT/CT Blood Specimen

Eligibility Criteria

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Inclusion Criteria

1. Histologically confirmed prostate adenocarcinoma.
2. Willing to undergo prostatectomy with or without lymph node dissection, and candidate for prostatectomy as determined by urologic oncology.
3. High-risk disease as defined as meeting 1 or more of the 3 following criteria:

1. Gleason score of 4+5 disease or higher.
2. Pelvic nodal metastases on PSMA PET.
3. Extracapsular extension or seminal vesicle invasion on MRI.
4. No evidence of distant metastatic disease as determined by PSMA PET. Nodal disease below the iliac bifurcation (clinical stage N1) is allowed.
5. 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).
6. Target tumor in the prostate measuring greater than 2 cm on MRI.
7. Age ≥18 years.
8. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%),
9. Demonstrates adequate organ function as defined below:

1. Platelets ≥100,000/mcL, independent of transfusions or growth factors within 3 months of treatment start.
2. Hemoglobin ≥10 g/dL, independent of transfusions or growth factors within 3 months of treatment start.
3. Absolute Neutrophil Count (ANC) ≥1,500/microliter (mcL).
4. Creatinine clearance Glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m\^2 , calculated using the Cockcroft-Gault equation.
5. Albumin ≥2.5 g/dL.
6. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3.0 x ULN.
7. Total bilirubin (TBIL) ≤2 x the institutional upper limit of normal (ULN). For participants with known Gilbert's Syndrome ≤3 x ULN is permitted.
10. Ability to understand and the willingness to sign a written informed consent document.
11. Participants must provide consent to comply to recommended radioprotection precautions during study.
12. Participants must use adequate contraception and not donate sperm while on study drug and for at least 14 weeks after the last study treatment.

Exclusion Criteria

1. Has received prior prostate cancer therapy.

a. Prior 5-alpha reductase inhibitors (e.g. finasteride, dutasteride) allowed if discontinued at least 3 weeks prior to treatment start.
2. 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.
3. Dry mouth that impacts the eating of food (i. e. requiring mouthwash prior to eating).
4. Concurrent 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.
5. 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.
6. 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.


1. Severe allergy to iodinated contrast.
2. Severe atherosclerosis from prior CT imaging study, or greater than 10 pack-year smoking history if no prior imaging available.
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Novartis

INDUSTRY

Sponsor Role collaborator

Thomas Hope

OTHER

Sponsor Role lead

Responsible Party

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Thomas Hope

Professor In Residence

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Thomas A Hope, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

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University of California, San Francisco

San Francisco, California, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Maya Aslam

Role: CONTACT

(415) 514-8987

Facility Contacts

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Maya Aslam

Role: primary

415-514-8987

Role: backup

877-827-3222

Other Identifiers

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25922

Identifier Type: -

Identifier Source: org_study_id

NCI-2025-04497

Identifier Type: REGISTRY

Identifier Source: secondary_id

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