Status:
Completed
Clinicaltrials.gov identifier:
Sponsor:
Fidia Farmaceutici S.p.A.
Enrollment:
60
Study Design:
Oncofid-P-B is a novel compound under development by Fidia Farmaceutici S.p.A. with specific binding to the CD44 receptor. This is a single-arm, multicenter European study consisting of weekly intravesical instillation of Oncofid-P-B for 12 weeks (intensive phase) followed by 12 monthly instillations (maintenance phase). Patients with CIS ± Ta-T1, unresponsive or intolerant to BCG, unwilling or unfit for cystectomy were enrolled. Patients were deemed BCG-refractory and were not BCG-unresponsive by current standards. Patients with muscle invasive bladder cancer (MIBC) and/or concomitant cancer of the upper urinary tract were excluded.
Rationale:
The urothelial membrane resists penetration of chemotherapeutic agents preventing effective therapy of non-muscle invasive bladder cancer (NMIBC). Oncofid-P-B is a novel intravesical agent consisting of paclitaxel conjugated to hyaluronic acid (HA). It is postulated that the HA moiety binds selectively to CD44 which is over-expressed on the surface of urothelial tumors allowing for increased paclitaxel activity. In vitro studies demonstrate greater cytotoxicity in cell lines with Oncofid-P-B compared to paclitaxel alone. A previous Phase I study established good tolerability and efficacy in a BCG-refractory CIS cohort treated with a weekly 6-week course. This study is a Phase II, single-arm trial evaluating the effects of an intensive or induction phase followed by a maintenance phase of treatment with Oncofid-P-B in patients with high risk, BCG unresponsive CIS+/- Ta or T1 disease.
Endpoints:
The safety and tolerability profile was the primary endpoint. The secondary endpoints were the antitumor activity of Oncofid-P-B measured at the end of the intensive phase and every three months during the maintenance phase, compliance with treatment, and evaluation of systemic absorption of Oncofid-P-B. The complete response rate was defined as a negative cystoscopy, negative biopsy of the urothelium (performed after the intensive phase or whenever a suspicious area was found) and a negative cytology.
Comments:
This phase II study is promising and demonstrated good safety and tolerability and early efficacy results on par with other investigational agents in the BCG-unresponsive NMIBC clinical space. Of note, seven patients only received a single induction course of BCG followed by additional chemotherapy and were enrolled in order to mitigate the future risk of disease progression and so it is conceivable that the response rates seen are higher than what would be seen in a truly BCG-unresponsive cohort. The initial results warrant further evaluate in Phase II/III studies.
Results:
Twenty-one patients were enrolled and twenty completed treatment and were evaluable. At study entry, 85% of patients had CIS only and 80% of all patients were unresponsive to BCG whereas 20% of all patients were intolerant to BCG. The compliance rate with the intensive treatment regimen was 91.6%. The complete response rate was 75% at the end of the intensive phase. The complete response rate was 65% at month 3 of maintenance therapy and was 40% at the end of the maintenance phase (15 months after treatment start). Ultimately, twelve patients did not respond and two had disease progression (one with lamina propria invasion and one with muscle invasion). Median time to failure (e.g. persistent CIS, disease relapse or progression) was 14.1 months in all patients. Eighteen (90%) patients experienced AEs and SAEs were only reported in two (10%) patients. One patient experienced death but not related to Oncofid-P-B and felt to be secondary to concomitant disease with squamous lung carcinoma. There was no systemic absorption of the drug.
