Efficacy of Durvalumab in Non-muscle-invasive Bladder Cancer

Sponsor
Hellenic GenitoUrinary Cancer Group
Study ID
NCT03759496
Phase
PHASE2
Status
Unknown

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Durvalumab — BIOLOGICAL
    Durvalumab is a human monoclonal antibody (mAb) of the immunoglobulin G (IgG) 1 kappa subclass

Study Details

Research Hypothesis Approximately 75% of patients with bladder cancer (BC) present with a disease confined to the mucosa (stage Ta, CIS) or submucosa (stage T1) (non-muscle invasive BC \[NMIBC\]). For high grade NMIBC, i.e. TaG3, T1G3 and CIS, intravesical bacillus Calmette-Guérin (BCG) immunotherapy is the treatment of choice, given that it prevents recurrence and reduces the odds of progression to MIBC. However, since initial BCG therapy fails in approximately 40% of patients over a 2-year period, new treatment options for these patients are of utmost importance. In that field of research durvalumab, a human monoclonal antibody that binds programmed cell death ligand-1 (PD-L1), demonstrated meaningful clinical activity as well as manageable safety profile in PD-L1-positive patients with BC, many of whom were heavily pretreated. Certain studies using systemic administration of anti-PD1 agents for BCG refractory NMIBC are ongoing. Nevertheless, intravesical administration may be advantageous, since selective bladder tumor uptake of monoclonal antibodies following intravesical administration, while this method results in negligible absorption in the circulation and, therefore, minimal risk of systemic toxicity. This notion is supported by the findings of a recent study of intravesical administration of recombinant adenovirus-mediated interferon-α2b gene therapy (rAd-IFNα), No rAd-IFNα DNA was detected in the blood. Furthermore, no systemic toxicity was reported in a phase II study using the same agent. The investigators, therefore, propose a phase II study of intravesical administration of durvalumab in patients with BCG refractory NMIBC. Since no safety or efficacy data specifically on intravesical administration of durvalumab exist, a run-in part will precede the main phase II, in order to confirm safety of the procedure and to reject a futility hypothesis, as described in the following sections of the protocol. Correlative studies of potential biomarkers in tumor tissue before and after durvalumab instillation are also proposed.

Key Dates

Start date
Nov 15, 2018
Status verified
Mar 2022
Primary completion
May 31, 2022
Completion
Dec 31, 2022

Study Design

Enrollment
39 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Durvalumab treated patients
    Subjects will receive up to 1000mg durvalumab (MEDI4736) via weekly intravesical administration, for up to a maximum of 6 weeks or until confirmed progression, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met.

Primary Outcome Measure

The maximum tolerated dose (MTD) of Durvalumab among 500mg, 750mg and 1000mg that will be given intravesically to patients with BCG-refractory NMIBC [ Time Frame: 6 months after trial initiation ]

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