A phase 1a/b dose-escalation and dose-expansion study to evaluate Lutetium-177-PSMA I&T (Lu-PSMA) with radiosensitising Capecitabine in patients with metastatic castration-resistant prostate cancer (mCRPC)

ACTRN 12623001072606

Brief Summary

This study aims to assess the effect of combining two different cancer treatments, Lu-PSMA and capecitabine, for the treatment of castration-resistant metastatic prostate cancer.

Intervention/Treatment

• Drug: Lu-PSMA
• Drug: Capecitabine

Inclusion Criteria

1. At least 18 years of age.
2. Metastatic adenocarcinomacancer arising from mucus-producing glands in organs of the prostate defined by:
   • Documented histopathology of prostate adenocarcinoma (without any features of neuroendocrine carcinomacancer arising from tissues that line organs) OR
   • A clinical diagnosis based on PSA elevation and typical imaging findings for metastatic prostate cancer.
3. Castration-resistant prostate cancer (defined as disease progressing despite castration by orchiectomyremoval of one or both testicles, also known as orchidectomy or ongoing luteinising hormone-releasing hormone agonist or antagonist).
4. Disease progression with rising PSA defined by PCWG3 criteria (sequence of 2 rising values at a minimum of 1-week intervals).
5. Disease progression after at least one taxane chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells in the mCRPC setting AND at least one novel androgen receptor signalling inhibitor (in the setting of either mCSPC or mCRPC). Patients with prostate cancer that has a known BRCA mutation must have had at least one PARP inhibitor therapy. If BRCA status is unknown patients will be eligible for inclusion.
6. Imaging evidence of metastatic disease documented with either bone scana type of medical imaging that uses a radioactive tracer to detect bone conditions or abnormalities or CT scan.
7. Significant PSMA avidity on PSMA PET/CT, defined as SUVmax >15 at a single site (regardless of lesion size) and SUV max >10 at sites of disease = 10mm (unless subject to factors explaining a lower uptake, e.g. respiratory motion, reconstruction artefact) without FDG discordance. Metastases subject to these criteria are for soft tissue disease (not bone metastases), and lymph node measurement taken from the short axis.
8. ECOG performance status:
   • Dose-escalation phase: 0-2.
   • Dose-expansion phase: 0-1.
9. Adequate renal function:
   • Creatinine clearance greater than or equal to 40mL/ min (defined by either Cockcroft-Gault formula or by nuclear medicinea specialised area of radiology that involves the use of radioactive substances in the diagnosis and treatment of disease renal scan).
10. Adequate liver function:
    • Bilirubin < 1.5 x upper limit of normal (ULN) (or if bilirubin is between 1.5 – 2x ULN, must have a normal conjugated bilirubin).
    • AST or ALT less than or equal to 2.0 x ULN (or less than or equal to 5.0 x ULN in the presence of liver metastases).
11. Adequate bone marrowsoft, spongy tissue found in bones that makes blood cells function:
    • Platelets greater than or equal to 100 x109 /L.
    • Haemoglobin greater than or equal to 90g/L (no red blood cell transfusion in last 4 weeks).
    • Neutrophilsa type of white blood cell that act as a first responder to infections in the body > 1.5 x109 /L.
12. Estimated life expectancy > 12 weeks.
13. Study treatment both planned and able to start within 21 days of registration.
14. Willing and able to comply with all study requirements (including both treatments: capecitabine and Lu-PSMA), and all required study assessments.
15. Signed, written, informed consent.