Testing [225Ac]Ac-PSMA-XT, a PSMA-targeted alpha therapy, in men with metastatic castration‑resistant prostate cancer.

A Clinical Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of [225Ac]Ac-PSMA-XT Injection in Patients With Metastatic Castration-resistant Prostate Cancer

This will try a PSMA-targeted radioactive drug called [225Ac]Ac-PSMA-XT to see if it is safe and helps men with metastatic castration‑resistant prostate cancer.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Shandong Cancer Hospital and Institute (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Jinan, Shandong)
• Trial ID: NCT07135102 on ClinicalTrials.gov

What this trial studies

This is a Phase 1 interventional study that gives an Actinium‑225 labeled PSMA ligand ([225Ac]Ac-PSMA-XT) to men with PSMA PET–positive metastatic castration‑resistant prostate cancer to determine safety, tolerability, and preliminary signs of benefit. Participants must have prior androgen-axis therapy and prior taxane chemotherapy or be unsuitable for taxanes, an ECOG performance status of 0–1, and adequate organ function. The study will monitor adverse events, laboratory measures, and early efficacy signals such as imaging and clinical progression. Treatment is administered at a single center and patients are followed for safety and response outcomes.

Who should consider this trial

Good fit: Ideal candidates are adult men with PSMA PET–positive metastatic castration‑resistant prostate cancer, ECOG 0–1, prior androgen‑axis therapy and at least one to two prior taxane regimens or proven taxane unsuitability, and adequate organ function.

Not a fit: Patients without PSMA expression on PET, those with poor performance status, significant organ dysfunction, or active conditions that preclude receiving radioligand therapy are unlikely to benefit.

Why it matters

Potential benefit: If successful, this targeted alpha therapy could shrink PSMA‑positive tumors and extend disease control for men with advanced, treatment‑resistant prostate cancer.

How similar studies have performed: Similar alpha‑emitter PSMA therapies such as [225Ac]PSMA‑617 have shown promising responses in early reports, but remain investigational and require more study.

Eligibility criteria

Inclusion Criteria:

1. have the ability to understand and sign an approved informed consent form (ICF).
2. \>= 18 years old.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4. have a life expectancy \>6 months.
5. have histological, pathological, and/or cytological confirmation of prostate cancer.
6. PSMA Positron Emission Tomography (PET)/Computed Tomography (CT) scan positive
7. have a castrate level of serum/plasma testosterone (\<50 ng/dL or \<1.7 nmol/L).
8. have received at least one NAAD (such as enzalutamide and/or abiraterone)； patients must have been previously treated undergone at least 1-2 prior taxane-based chemotherapy regimens or be unsuitable for taxane therapy (unsuitability includes contraindications, investigator-determined ineligibility, or patient refusal) in mCRPC stage.
9. progressive mCRPC.
10. have adequate organ function。
11. Subjects of childbearing potential voluntarily use an effective method of contraception, such as condoms, oral or injectable contraceptives, Intra-uterine device（IUD）,etc., during treatment and within 6 months of the last use of the trial drug.

Exclusion Criteria:

1. Previous treatment with any of the following within 6 months of enrollment: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation. Previous PSMA-targeted radioligand therapy is not allowed.

   Known other malignancies.
2. Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biological therapy within 28 days prior to day of enrollment.
3. Known hypersensitivity to the components of the study therapy or its analogs.
4. A superscan as seen in the baseline bone scan.
5. Patients with a history of Central Nervous System (CNS) metastases.
6. Uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, cardiac arrhythmia, or other severe complications.

Where this trial is running

Jinan, Shandong

• Cancer Hospital of Shandong First Medical University — Jinan, Shandong, China (Recruiting)

Conditions Metastatic Castration-Resistant Prostate Cancer Patients