SUBDUE-3: A Phase 0 study of SUB-urothelial DUrvalumab-Zirconium to investigate local and systemic distribution of Durvalumab when injected in the sub-urothelium in adult subjects with muscle invasive bladder cancer or high-risk non-muscle invasive bladder tumours.
SUBDUE-3: A Phase 0 study of SUB-urothelial DUrvalumab-Zirconium to investigate local and systemic distribution of Durvalumab when injected in the sub-urothelium of adult subjects with muscle invasive bladder cancer or high-risk non-muscle invasive bladder cancer
South Metropolitan Health Service, Fiona Stanley Hospital, 11 Robin Warren Drive, MURDOCH WA 6150
3 participants
Feb 10, 2025
Interventional
Conditions
Summary
This study aims to investigate the local (bladder wall) and systemic (liver, kidney, lung, bone marrow) distribution of durvalumab with a radioactive isotope when injected in the sub-urothelium for Bladder Cancer (SUBDUE-3) Who is it for? You may be eligible to join this study if you are aged 18 years or above with a diagnosis of muscle invasive bladder cancer or high-risk non-muscle invasive (T1, high grade Ta, carcinoma in-situ) bladder tumours and scheduled for a cystectomy. Study details All participants will receive a single dose of 89Zr-Durvalumab injected to their bladder. Participants will have positron emission tomography (PET) imaging at pre-determined timepoints to visualise the distribution of the drug over time up to 7 days post injection. Blood samples will be taken and any adverse events will be recorded for up to 2 weeks post-cystectomy. It is hoped that SUBDUE-3 will contribute to the further understanding and development of immunotherapy treatments being delivered directly into the wall of the bladder with the aim of achieving bladder preservation in localised bladder cancer. This trial will contribute to the understanding and further development of sub-urothelial immunotherapy as a potential treatment for patients with bladder cancer.
Eligibility
Inclusion Criteria9
- Study population: Participants with either muscle invasive bladder cancer or high-risk non-muscle invasive (T1, high grade Ta, carcinoma in-situ) bladder tumours scheduled for cystectomy,
- Capable of giving signed informed consent.
- Willingness to undergo the described procedure and study schedule of investigations
- Age greater than or equal to 18 years.
- Have either MIBC or high-risk NMIBC (T1, high-grade Ta, carcinoma in situ) scheduled for radical cystectomy (including neo-adjuvant chemotherapy).
- ECOG performance status of less than 2.
- Life expectancy of greater than or equal to 6 months.
- Adequate organ and marrow function.
- Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients
Exclusion Criteria13
- Concurrent cancer therapy with the same biological intent that may interact with durvalumab. Neo-adjuvant chemotherapy allowed.
- Any unresolved toxicity NCI CTCAE (version 5.0) Grade greater than or equal to 2 from previous anticancer therapy.
- Major surgical procedure within 28 days prior to administration of durvalumab.
- History of allogeneic organ transplantation.
- Active or prior documented autoimmune or inflammatory disorders.
- History of active primary immunodeficiency.
- Active tuberculosis, hepatitis B, hepatitis C.
- Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab
- Receipt of live attenuated vaccine within 30 days prior to administration of durvalumab. Patients should not receive live vaccine up to 30 days after durvalumab administration
- Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab.
- Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
- Prior randomisation or treatment in a previous durvalumab or other immunotherapy clinical study.
- Previous administration of any radionuclide within 10 half-lives of the same
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Interventions
Dose: 25mls of 89Zr-Durvalumab constituted as: a)37 Megabecquerels (MBq) in 4mg of Durvalumab in 4mls of 0.9% saline, combined with b)21mg of Durvalumab in 21mls of 0.9% saline Duration: Single administration of 89Zr-Durvalumab constituted as prescribed dose. The prescribed dose is administered during flexible cystoscopy two weeks prior to cystectomy. Patients will subsequently have 4 PETCT scans and blood tests over 1 week to determine the local and systemic distribution of 89Zr-durvalumab when injected in the sub-urothelium Mode: 25 sub-urothelial 1ml injections distributed evenly across the bladder, including the trigone. Injected in 1mL aliquots throughout the bladder under general anaesthesia using a a 5Fr Bonee needle via a 22Fr rigid cystoscope followed by urethral catheterisation prior to cystectomy. Subsequent PET imaging will be obtained at: a) 1-3 hours (bladder only) b) 24 hours (whole body and dedicated pelvic scan) c) 72 hours (whole body) d) 5-7 days (whole body) Blood sampling will be undertaken along with the imaging time point to evaluate for systemic 89Zr-durvalumab bioavailibity using a gamma counter. The urinary catheter bag will be sent to medical physics at the time of first imaging to calculate the urinary radiation dose, and the catheter will be removed following the first scan.
Locations(1)
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ACTRN12624001245583