SUBurothelial DUrvalumab injEction-1 (SUBDUE-1)
A phase 1 open label dose-escalation study to evaluate the tolerability, safety, and immunological efficacy of sub-urothelial durvalumab injection in adult subjects with muscle invasive bladder cancer or high-risk non-muscle invasive bladder tumours.
South Metropolitan Health Service
12 participants
Dec 9, 2019
Interventional
Conditions
Summary
This study aims to evaluate the tolerability and safety of a sub-urothelial injection of durvalumab for Bladder Cancer. 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. Participants will be allocated to receive a single dose of durvalumab to their bladder. The dose will be decided according to the dose-escalation schedule. Participants will be required to answer a series of questions in regards to their experience whilst receiving care, and consent to their removed tissue being used for this research. It is hoped this research will provide an alternative, safer and better tolerated treatment option for people with high-risk non-muscle invasive bladder cancer.
Eligibility
Inclusion Criteria5
- 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, who have refused or are ineligible for systemic neo-adjuvant chemotherapy.
- Age equal to or greater than 18 years
- ECOG performance less than 2
- Life expectancy equal to or greater than 6 months
- Adequate organ and marrow function
Exclusion Criteria20
- Patients who have received neo-adjuvant chemotherapy
- Any concurrent cancer therapy of the same biological intent that may interact with durvalumab.
- Participation in another clinical study with an investigational product during the last 28 days
- Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade equal to or greater than 2 from previous anticancer therapy
- Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of sub-urothelial durvalumab
- Major surgical procedure within 28 days prior to administration of durvalumab, excluding trans-urethral resection of bladder tumour
- History of allogenic organ transplantation
- Active or prior documented autoimmune or inflammatory disorders
- History of another primary malignancy within the last 5 years, excluding non-melanomatous skin cancer
- 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 sub-urothelial
- 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 durvalumab
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Interventions
Dose: Three possible doses of durvalumab (25mg, 75mg, 150mg) will be studied to identify the recommended phase II dose. The selected dose will be diluted in 25mls of normal saline. Duration: Single administration of prescribed dose as per dose escalation schedule. The prescribed dose is administered during flexible cystoscopy two weeks prior to cystectomy. Mode: Multiple sub-urothelial 1ml injections distributed evenly across the bladder, including the trigone. Residual tumour, if present will be included. Dose will be determined using a 3x3 dose-escalation technique, up to a maximum dose of 150mg. A minimum of 3 subjects will be enrolled in each dose-level cohort, commencing at 25mg. If no dose-limiting toxicities (DLTs) are observed in the first 3 subjects during the DLT-evaluation period, dose-escalation will continue to the next higher dose cohort. Formal histopathology review of cystectomy specimens will be undertaken prior to dose escalation. If 1 of 3 patients in a dose-level cohort experiences a DLT, that dose-level cohort will be expanded to a total of 6 patients. If no more than 1 of 6 subjects in the dose-level cohort experiences a DLT, dose-escalation will continue to the next higher dose-level cohort. If greater than or equal to 2 subjects in the first dose cohort experience a DLT during the DLT evaluation period, the maximum tolerated dose (MTD) will be exceeded and no further subjects will be enrolled into that dose-level cohort. If this occurs, the preceding dose-level cohort will be evaluated for the MTD and a total of 6 subjects will be treated at the preceding dose level. If the highest dose-level is reached and no more than 1 of the initial 3 subjects experiences a DLT, that dose-level cohort will be expanded to a total of 6 subjects. Determination of the recommended phase 2 dose (RP2D) will be the dose level where less than or equal to 1 out of 6 patients experience DLT at the highest dose level below the maximally administered dose.
Locations(1)
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ACTRN12620000063910