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 cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs treatments, Lu-PSMA and capecitabine, for the treatment of castration-resistant metastatic prostatea walnut-shaped gland in the male reproductive system that is responsible for producing semen - a bodily fluid that acts as a vessel for sperm transport during ejaculation 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 diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results based on PSA elevation and typical imagingtests that create detailed images of areas inside the body 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 hormonea chemical substance produced by glands in the endocrine system that regulates various functions in the body 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 inhibitora type of targeted therapy that blocks the poly (ADP-ribose) polymerase (PARP) enzyme, which plays a role in DNA repair - this can stop cancer cells from repairing themselves 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 tissuetissue/the material that joins, holds up or surrounds inside body parts such as fat, muscle, ligaments and lining around joints disease (not bone metastases), and lymph nodea small lump or mass of tissue in your body 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:
    • Plateletssmall disc-shaped blood cells that clump together to form clots to stop bleeding greater than or equal to 100 x109 /L.
    • Haemoglobin greater than or equal to 90g/L (no red bloodthe red bodily fluid that transports oxygen and other nutrients around the body 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 consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment..