Alpha-Emitting Radionuclide or Beta-Emitting Radionuclide With Metastasis-Directed Stereotactic Body Radiotherapy for the Treatment of Recurrent, Oligometastatic Prostate Adenocarcinoma

About

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.

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase 2

Eligibility

Gender

Male

Healthy Volunteers

No

Minimum Age

18 Years

Maximum Age

N/A

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