Combination of Radium-223 and Lutetium-177 PSMA-I&T in Men With Metastatic Castration-Resistant Prostate Cancer: Phase I/II Study

• Status: Not yet recruiting
• Trial end date: 2026-12-01
• Target enrollment: 0
• Participant gender: Male

Summary

This clinical trial will evaluate the safety of Radium-223 in combination with 177Lu-PSMA-I&T in metastatic castration-resistant prostate cancer: Phase I/II study

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Peter MacCallum Cancer Centre, Australia

Criteria

Inclusion Criteria:

• Patient must be ≥ 18 years of age and must have provided written informed consent.

• Histologically or cytologically confirmed adenocarcinoma of the prostate, OR unequivocal diagnosis of metastatic prostate cancer. (i.e. involving bone or pelvic lymph nodes or para-aortic lymph nodes) with an elevated serum PSA.

• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2

• Patients must have progressed on ≥ 1 second-generation AR-targeted agent (e.g., enzalutamide, abiraterone, or apalutamide).

• Patients must have progressive disease for study entry. PCWG3 defines this as any one of the following:

• PSA progression: minimum of two rising PSA values from a baseline measurement with an interval of ≥ 1 week between each measurement.

• Soft tissue progression as per RECIST 1.1 criteria

• Bone progression: ≥ 2 new lesions on bone scan

• Symptomatic progression eg. Bone pain

• At least three weeks since the completion of surgery or radiotherapy prior to registration.

• Prior surgical orchiectomy or chemical castration maintained on luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist).

• Serum testosterone levels ≤ 1.75nmol/L (≤ 50ng/dL) within 28 days before registration.

• Significant PSMA avidity on PSMA PET/CT, defined as a minimum uptake of SUVmax 20 at a site of disease, and SUVmax >10 at sites of measurable disease >10mm (unless subject to factors explaining a lower uptake, e.g. respiratory motion, reconstruction artefact).

• ≥ 2 bone metastases must be present on bone scintigraphy which have not been previously treated with radiotherapy.

• No contraindication to treatment with a bone antiresorptive agent such as denosumab or zoledronic acid.

• Patients must have adequate bone marrow, hepatic and renal function documented within 28 days prior to registration, defined as:

• Haemoglobin ≥ 90 g/L independent of transfusions (no red blood cell transfusion in last four weeks)

• Absolute neutrophil count ≥ 1.5x10^9/L

• Platelets ≥ 150 x10^9/L

• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) except for patients with known Gilbert's syndrome, where this applies for the unconjugated bilirubin component.

• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN if there is no evidence of liver metastasis or ≤ 5 x ULN in the presence of liver metastases

• Albumin ≥ 25 g/L

• Adequate renal function: patients must have a creatinine clearance estimated of ≥ 40 mL/min using the Cockcroft Gault equation

• Sexually active patients are willing to use medically acceptable forms of barrier contraception.

• Willing to undergo biopsies, if disease is considered accessible and biopsy is feasible.

• Willing and able to comply with all study requirements, including all treatments and the timing and nature of all required assessments.

Exclusion Criteria:

Patients who meet any of the following criteria will be excluded from study entry:

• Superscan on Bone scan (WBBS) or diffuse marrow involvement on PSMA PET/CT

• Prior treatment with 223Ra or 177Lu-PSMA.

• Has not received more than one previous line of chemotherapy for the treatment of metastatic prostate cancer.

• Sites of discordant FDG-positive disease defined by minimal PSMA-expression and no uptake on WBBS (for bone metastases).

• Other malignancies within the previous 2 years other than basal cell or squamous cell carcinomas of skin or other cancers that are unlikely to recur within 24 months.

• Symptomatic brain metastases or leptomeningeal metastases.

• Patients with symptomatic or impending cord compression unless appropriately treated beforehand and clinically stable for ≥ four weeks.

• Concurrent illness, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety.