Status:
Completed
Clinicaltrials.gov identifier:
Sponsor:
FKD Therapies Oy
Enrollment:
40
Study Design:
This was a Phase II multicenter study targeting BCG unresponsive high grade NMIBC patients and refused to undergo radical cystectomy were randomized to one of two different Instiladrin viral particle dosages for their disease. The patients received treatments every 3 months for a total of 4 treatments if they continued to respond to therapy without a recurrence.
Rationale:
Instiladrin is a non-replicating recombinant adenovirus vector containing the human interferon alpha-2b gene. It is administered intravesically and serves as a gene transfer vector and is formulated with Syn3, a polyamide surfactant that enhances the adenoviral transduction of the bladder lining. This allows for more reliable viral transduction of the IFNα-2b gene and ultimately production of IFNα-2b in the bladder. IFNα-2b is believed to be a key early cytokine in the immune response initiated by BCG and Instiladrin allows for more reliable production of this cytokine.
Endpoints:
The primary endpoint was freedom from high grade recurrence-free survival (RFS) at 12 months defined by negative bladder biopsies.
Comments:
This trial is limited for many reasons including the small number of patients and the lack of a comparison control group given the heterogeneity of this disease and the multiple pathologic cohorts. Interestingly, the RFS was least in the pure CIS patients at 12 months which is unfortunate since CIS that no longer responds to BCG some is among the most difficult to treat.. Furthermore, without a comparison control group, it is unknown if the high RFS seen at 12 months in Ta or T1 disease was due to the Instiladrin or to the resection of disease. However, it was tolerable and the phase III trial has already been completed and so results are eagerly anticipated.
Results:
The disease states of the 40 patients consisted of 21 pure CIS, 4 CIS + Ta, 5 CIS + T1, 4 Ta, and 6 T1. Overall, the 12-month high grade RFS was 35% and was comparable between the two groups that only differed in the number of viral particles received. RFS at 12 months was highest in Ta or T1 patients at 50% and lowest in pure CIS patients at 29%. On long-term follow-up, seven patients who recurred with disease on the trial died within a median of 16 months. Although none of the deaths was thought to be treatment-related, at least two of the deaths were due to disease progression. The most common treated-related adverse events (AEs) were urgency (40%), dysuria (40%), and fatigue (33%). However, none of the patients experienced grade 4-5 AEs.
