NCT07150715

Brief Summary

This phase II trial compares the use of 225Ac-PSMA-617 to 177Lu-PSMA-617, along with stereotactic body radiotherapy for the treatment of prostate cancer that has come back after a period of improvement (recurrent) and that has spread from where it first started (primary site) to multiple other places in the body (oligometastatic). 225Ac-PSMA-617 and 177Lu-PSMA-617 are radioactive drugs. They bind to a protein called a PSMA receptor, which is found on some prostate tumor cells. 225Ac-PSMA-617 or 177Lu-PSMA-617 builds up in these cells and gives off either alpha or beta radiation that may kill them. It is a type of radioconjugate and a type of PSMA analog. Stereotactic body radiation therapy (SBRT) is a type of external radiation therapy that uses special equipment to position a patient and precisely deliver radiation to tumors in the body (except the brain). The total dose of radiation is divided into smaller doses given over several days. This type of radiation therapy helps spare normal tissue. Giving 225Ac-PSMA-617 or 177Lu-PSMA-617 and metastasis directed stereotactic body radiotherapy may be effective in treating patients with recurrent, oligometastatic prostate cancer.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
107

participants targeted

Target at P50-P75 for phase_2

Timeline
67mo left

Started Dec 2025

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress7%
Dec 2025Oct 2031

First Submitted

Initial submission to the registry

August 25, 2025

Completed
8 days until next milestone

First Posted

Study publicly available on registry

September 2, 2025

Completed
3 months until next milestone

Study Start

First participant enrolled

December 12, 2025

Completed
4.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 31, 2030

Expected
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

October 31, 2031

Last Updated

December 17, 2025

Status Verified

December 1, 2025

Enrollment Period

4.9 years

First QC Date

August 25, 2025

Last Update Submit

December 15, 2025

Conditions

Outcome Measures

Primary Outcomes (1)

  • Progression free survival (PFS)

    A progression event will be based on prostate specific membrane antigen positron emission tomography/ computed tomography findings triggered either by a prostate specific antigen rise or at the timepoint defined by 24 months measured from the final radionuclide infusion (i.e., second infusion of 177Lu-PSMA-617 and first infusion of 225Ac-PSMA-617). The Kaplan-Meier (KM) method will be used to summarize PFS and log-rank test will be used to compare PFS between the two arms.

    From the date of randomization to the date of disease progression or death, whichever happens earlier, up to 5 years

Secondary Outcomes (8)

  • Incidence of adverse events (AEs)

    From time of randomization, up to 5 years

  • Androgen deprivation therapy free survival

    Up to 5 years

  • Time to locoregional progression

    Up to 5 years

  • Time to new metastasis

    Up to 5 years

  • Overall survival

    Up to 5 years

  • +3 more secondary outcomes

Study Arms (2)

Arm I (177Lu-PSMA-617)

EXPERIMENTAL

Patients receive 177Lu-PSMA-617 IV, over 1-10 minutes, on day one of each cycle. Cycles repeat every 6 weeks for 2 cycles. 4-6 weeks after completion of 177Lu-PSMA-617 patients receive 68Ga-PSMA-11 IV and undergo PSMA PET/CT scan. Within 4 weeks of the scan, patients receive SBRT, for 1-5 treatments, over 1- 1- days. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients undergo PSMA PET/CT scan and blood sample collection throughout the study.

Drug: Actinium Ac 225 Vipivotide TetraxetanProcedure: Biospecimen CollectionDrug: Lutetium Lu 177 Vipivotide TetraxetanProcedure: PSMA PET-CT ScanRadiation: Stereotactic Body Radiation Therapy

Arm II (225Ac-PSMA-617)

EXPERIMENTAL

Patients receive 225Ac-PSMA-617 IV once. 4-6 weeks after completion of 225Ac-PSMA-617 patients receive 68Ga-PSMA-11 IV and undergo PSMA PET/CT scan. Within 4 weeks of the scan, patients receive SBRT, for 1-5 treatments, over 1- 1- days. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients undergo PSMA PET/CT scan and blood sample collection throughout the study.

Drug: Actinium Ac 225 Vipivotide TetraxetanProcedure: Biospecimen CollectionOther: Gallium Ga 68 GozetotideProcedure: PSMA PET-CT ScanRadiation: Stereotactic Body Radiation Therapy

Interventions

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection
Arm I (177Lu-PSMA-617)Arm II (225Ac-PSMA-617)

Given IV

Also known as: (68)Ga labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC, (68)Ga-labeled Glu-urea-Lys(Ahx)-HBED-CC, (68)Ga-PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC, (68)Gallium-PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC, (68Ga)Glu-urea-Lys(Ahx)-HBED-CC, 68Ga-DKFZ-PSMA-11, 68Ga-HBED-CC-PSMA, 68Ga-labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC, 68Ga-PSMA, 68Ga-PSMA-11, 68Ga-PSMA-HBED-CC, [68Ga] Prostate-specific Membrane Antigen 11, [68Ga]GaPSMA-11, AAA 517, AAA-517, AAA517, Ga PSMA, Ga-68 labeled DKFZ-PSMA-11, Ga-68 labeled PSMA-11, GA-68 PSMA-11, Gallium Ga 68 PSMA-11, Gallium Ga 68-labeled PSMA-11, GALLIUM GA-68 GOZETOTIDE, Gallium-68 PSMA, Gallium-68 PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC, GaPSMA, PSMA-HBED-CC GA-68
Arm II (225Ac-PSMA-617)

Given IV

Also known as: 177Lu-labeled PSMA-617, 177Lu-PSMA-617, AAA 617, AAA-617, AAA617, Lu177-PSMA-617, Lutetium Lu 177-PSMA-617, LUTETIUM LU-177 VIPIVOTIDE TETRAXETAN, Lutetium-177-PSMA-617, Pluvicto
Arm I (177Lu-PSMA-617)

Undergo PSMA PET/CT scan

Also known as: PET-CT (PSMA), Prostate-specific Membrane Antigen PET-CT, PSMA PET-CT
Arm I (177Lu-PSMA-617)Arm II (225Ac-PSMA-617)

Undergo SBRT

Also known as: SABR, SBRT, Stereotactic Ablative Body Radiation Therapy
Arm I (177Lu-PSMA-617)Arm II (225Ac-PSMA-617)

Given IV

Also known as: 225Ac-labeled PSMA-617, 225Ac-PSMA-617, 225Ac-Vipivotide Tetraxetan, Actinium (225AC) PSMA-617, Actinium Ac 225 PSMA-617, Actinium Ac 225-PSMA-617, VIPIVOTIDE TETRAXETAN ACTINIUM AC-225
Arm I (177Lu-PSMA-617)Arm II (225Ac-PSMA-617)

Eligibility Criteria

Age18 Years+
Sexmale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Oligorecurrent prostate cancer as determined by the presence of 1-5 asymptomatic lesions outside the prostate or prostate bed identified on PSMA PET/CT by local readers
  • Serum testosterone \> 150 ng/dL
  • Age ≥ 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • No indication for urgent or emergent radiation
  • Histological confirmation of prostate adenocarcinoma (histology from original treatment acceptable)
  • White blood cell count ≥ 2.5 × 109/L
  • Platelets ≥ 100 × 109/L
  • Hemoglobin ≥ 9 g/dL
  • Total bilirubin ≤ 1.5 × institutional upper limits of normal (ULN) or up to 3 × ULN if known history of Gilbert's syndrome
  • Alanine aminotransferase or aspartate aminotransferase ≤ 3.0 × ULN or ≤ 5.0 × ULN for patients with liver metastases
  • Glomerular filtration rate creatinine-cystatin C (GFRcr-cys) ≥ 60 mL/min 1.73m2 using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) 2021 equation
  • Serum albumin \> 3.0 g/dL
  • Partner and patient must use a method of birth control with adequate barrier protection, deemed acceptable by the principal investigator during the study and for 3 months after last study drug administration
  • Ability to understand, and willingness to sign, the written informed consent

You may not qualify if:

  • Patients with neuroendocrine or small cell carcinoma of the prostate
  • Patients with castrate-resistant disease (i.e., prostate specific antigen \[PSA\] \> 0.5 ng/mL with serum testosterone \<150 ng/dL)
  • Patients who received androgen deprivation therapy or cytotoxic chemotherapy within 6 months of trial enrolment
  • Concurrent systemic therapy for a solid organ malignancy
  • Spinal cord compression
  • Inability to lie flat
  • Known hypersensitivity to components of 177-Lu-PSMA-617 or 225-Ac-Lu-PSMA-617
  • Inadequate renal function of GFRcr-cys \< 60 mL/min 1.73m2 using the CKD-EPI 2021equation
  • Total bilirubin \> 1.5 × ULN or \> 3.0 × ULN if known history of Gilbert's syndrome
  • Alanine aminotransferase or aspartate aminotransferase \> 3 × ULN (or 5 × ULN for patients with known liver metastases)
  • De novo oligometastatic disease

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

RECRUITING

MeSH Terms

Interventions

(225)Ac-PSMA-617ActiniumPSMA-617Specimen Handlinggallium 68 PSMA-1168Ga-DKFZ-PSMA-11PluvictoRadiosurgery

Intervention Hierarchy (Ancestors)

Actinoid Series ElementsElements, RadioactiveElementsInorganic ChemicalsMetals, HeavyRadioisotopesIsotopesMetalsClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisInvestigative TechniquesRadiotherapyTherapeuticsStereotaxic TechniquesNeurosurgical ProceduresSurgical Procedures, Operative

Study Officials

  • Amar Kishan

    UCLA / Jonsson Comprehensive Cancer Center

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 25, 2025

First Posted

September 2, 2025

Study Start

December 12, 2025

Primary Completion (Estimated)

October 31, 2030

Study Completion (Estimated)

October 31, 2031

Last Updated

December 17, 2025

Record last verified: 2025-12

Locations