Vicinium Treatment for Subjects With Non-muscle Invasive Bladder Cancer Previously Treated With BCG
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|ClinicalTrials.gov Identifier: NCT02449239|
Recruitment Status : Recruiting
First Posted : May 20, 2015
Last Update Posted : February 5, 2018
|Condition or disease||Intervention/treatment||Phase|
|Bladder Cancer||Biological: Vicinium||Phase 3|
Bladder cancer is the 6th most common cancer in the United States, affecting more men than women. The usual first treatment for NMIBC (Ta, T1, and CIS) is transurethral resection of the bladder tumors followed by intravesical immunotherapy, most commonly with bacillus Calmette-Guérin (BCG).
Because of the high risk for development of muscle invasive disease, cystectomy is recommended for CIS and high-grade Ta and T1 patients who experience disease recurrence following intravesical therapy. For patients unable or unwilling to undergo cystectomy, treatment options are limited.
Vicinium contains the active pharmaceutical ingredient VB4-845, which is a recombinant fusion protein produced in Escherichia coli (E. coli) that expresses a humanized single-chain antibody fragment specific for the epithelial cell adhesion molecule (EpCAM) antigen linked to ETA(252-608). Once bound to the EpCAM antigen on the surface of carcinoma cells, Vicinium is internalized through an endocytic pathway. The ETA(252-608) is cleaved off and induces cell death by irreversibly blocking protein synthesis.
In vitro and in vivo pharmacology demonstrated that Vicinium exhibits potent activity [inhibitory concentration 50% (IC50) = 0.001 - 10 pM] against numerous cell lines and effectively inhibits tumor growth in several human xenograft animal models. A Phase 2 study evaluated once-weekly instillations of Vicinium 30 mg over 6 or 12 weeks, followed by up to 3 maintenance cycles (3 once-weekly instillations followed by a 9-week drug-free period) in 45 subjects with histologically-confirmed TCC of the bladder and residual CIS with or without concurrent Ta or T1 who were refractory or intolerant to BCG. A complete response (defined as no histological evidence of disease and negative urine cytology at the 3-monthly evaluations) was achieved by 44% of subjects, and 16% of subjects remained disease-free at 1-year. A post-study assessment found that these subjects were still disease-free at 18-25 months. The median time to recurrence was 134 days longer in subjects who received 12 weeks of induction therapy compared to 6 weeks.
This is an open-label, non-randomized, multicenter study in adults with NMIBC, specifically CIS (with or without papillary disease), high-grade Ta or any grade T1 papillary disease, who have previously failed BCG treatment (i.e., not those who are intolerant) with or without interferon. The study consists of a Screening period, a 12-week Induction Phase, and a Maintenance Phase of up to 21 monthly cycles for a total treatment period of up to 104 weeks. This is an outpatient study, but all treatments are administered in the study clinic.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||134 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Open-Label, Multicenter, Ph 3 Study to Evaluate the Efficacy and Tolerability of Intravesical Vicinium™ in Subjects With Non Muscle-Invasive Carcinoma in Situ and/or High-Grade Papillary Disease of the Bladder Treated With BCG|
|Study Start Date :||August 2015|
|Estimated Primary Completion Date :||December 2018|
|Estimated Study Completion Date :||March 2019|
Induction - 30 mg of Vicinium in 50 mL of saline administered twice weekly (BIW) for 6 weeks followed by once weekly for 6 weeks, for a total of 12 weeks.
Maintenance - 30 mg of Vicinium in 50 mL of saline administered once weekly every other week for up to 104 weeks.
Other Name: VB4-845
- Complete response rate [ Time Frame: Up to 24 months ]Complete response rate in patients with CIS with or without resected papillary disease following initiation of Vicinium therapy
- Recurrence Rate [ Time Frame: Patients will be followed for up to 104 weeks ]Number of subjects with recurrence of high-grade disease, tumor progression to muscle invasive bladder cancer, cystectomy for any reason, or death, whichever occurs first.
- Event-free survival [ Time Frame: Time to event endpoint; patients will be followed for up to 104 weeks ]Interval from the date of first dose of study treatment to persistent high-grade disease or low grade T1 if that was the baseline disease, high-grade disease tumor recurrence, tumor progression to muscle invasive bladder cancer, cystectomy for any reason, or death
- Number of patients with adverse events as a measure of tolerability [ Time Frame: Every 4 weeks up to 104 weeks ]Frequency and severity of adverse events
- Changes in ECG [ Time Frame: Every 4 weeks up to 104 weeks ]Changes in ECG from baseline
- Changes in vital signs [ Time Frame: Every 4 weeks up to 104 weeks ]Changes in vital signs from baseline
- Changes in laboratory or physical examination [ Time Frame: Every 4 weeks up to 104 weeks ]Changes in laboratory or physical examination from baseline
- Complete response rate [ Time Frame: Months 3, 6, 9, 12, 15,18, 21 and 24 ]Complete response rate in subjects after 3, 6, 9, 12, 15, 18, 21, and 24 months of Vicinium therapy.
- Time to cystectomy [ Time Frame: Time to event endpoint; patients will be followed for up to 104 weeks ]Number of weeks from the date of first dose of study treatment to physical removal of the bladder
- Time to disease recurrence [ Time Frame: Time to event endpoint; patients will be followed for up to 104 weeks ]Number of weeks from the date of the first documented no histological evidence of high-grade disease at the end of the Induction Phase to the date of first high grade disease recurrence
- Time to progression [ Time Frame: Time to event endpoint; patients will be followed for up to 104 weeks ]Number of weeks from date of first dose of study treatment to the date of invasive disease being determined and documented
- Progression-free survival [ Time Frame: Time to event endpoint; patients will be followed for up to 104 weeks ]Number of weeks from the date of first dose of study treatment to the date of invasive disease being determined and documented or death due to any cause
- Overall survival [ Time Frame: Time to event endpoint; patients will be followed for up to 104 weeks ]Number of weeks from the date of first dose of study treatment to death due to any cause
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02449239
|Contact: Gary Conboyfirstname.lastname@example.org|
|Contact: David Brooks, MD, PhDemail@example.com|
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