Recruiting
Phase 2

225Ac-PSMA-617 vs. 177Lu-PSMA-617

Sponsor:

Jonsson Comprehensive Cancer Center

Code:

NCT07150715

Conditions

Oligometastatic Prostate Adenocarcinoma

Recurrent Prostate Adenocarcinoma

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Actinium Ac 225 Vipivotide Tetraxetan

Biospecimen Collection

Gallium Ga 68 Gozetotide

Lutetium Lu 177 Vipivotide Tetraxetan

PSMA PET-CT Scan

Study Details

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.

Conditions

Oligometastatic Prostate Adenocarcinoma

Recurrent Prostate Adenocarcinoma

Study ID

NCT07150715

Start date

Dec 12, 2025

Status verified date

Dec, 2025

Completion date

Oct 31, 2031

Anticipated

Primary completion date

Oct 31, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Design

Enrollment

107 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm I (177Lu-PSMA-617)

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.

experimental: Arm II (225Ac-PSMA-617)

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.

Interventions

Actinium Ac 225 Vipivotide Tetraxetan

Given IV

Biospecimen Collection

Undergo blood sample collection

Gallium Ga 68 Gozetotide

Given IV

Lutetium Lu 177 Vipivotide Tetraxetan

Given IV

PSMA PET-CT Scan

Undergo PSMA PET/CT scan

Stereotactic Body Radiation Therapy

Undergo SBRT

Primary outcome measure

  • Progression free survival (PFS) [ Time Frame: From the date of randomization to the date of disease progression or death, whichever happens earlier, up to 5 years ]

Central Contacts and Locations

Central contacts

Christy Palodichuk

3107942971cpalodichuk@mednet.ucla.edu

Care Felix

310-825-9771cfelix@mednet.ucla.edu

Locations

UCLA / Jonsson Comprehensive Cancer Center

Recruiting

Los Angeles, California, United States, 90095

Contacts

Christy Palodichuk

310-825-9775cpalodichuk@mednet.ucla.edu

Care Felix

3108259771cfelix@mednet.ucla.edu

Principal Investigator:

Amar Kishan, MD

More Information

Sponsor

Jonsson Comprehensive Cancer Center

Last update posted

Dec 17, 2025

Last verified

Dec, 2025

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Jonsson Comprehensive Cancer Center on 2025-12-17.