Study of Vicinium for Treating Patients With Non-Invasive Urothelial Carcinoma In Situ

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and tolerability of Vicinium when administered as a monotherapy intravesical instillation in patients with non-invasive urothelial carcinoma in situ (CIS) who failed previous treatment with Bacille Calmette Guérin (BCG).

Detailed Description
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A phase II study was performed to assess the efficacy and tolerability of intravesical Vicinium in patients with urothelial carcinoma in situ of the bladder. Bacillus Calmette-Guérin treatment had previously failed in all patients. A total of 46 patients were treated with Vicinium with half being administered 30mg/dose once per week for 6 weeks (cohort 1) and the other half (cohort 2) the same dose but administered once per week for 12 consecutive weeks. Disease assessments consisting of urine cytology, cystoscopy and, if indicated, biopsy were performed at 3 month intervals. Patients that were disease-free at the assessment time point were allowed to continue treatment in the maintenance phase which consisted of three weekly doses, followed by 9 weeks of no treatment. As long as the patient remained disease-free, treatment continued for a total of one year.

Official Title
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Phase II Study to Evaluate the Efficacy and Tolerability of Intravesical Vicinium™ in Patients With Non-Invasive Urothelial Carcinoma in Situ (CIS) Previously Treated With Bacille Calmette-Guérin (BCG)

Conditions
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Urinary Bladder Cancer, Bladder Cancer, Bladder Neoplasms, Bladder Tumors

Intervention / Treatment
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* Drug: Vicinium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Disease Characteristics The patient must be male or female 18 years of age or older. The patient must have histologically-confirmed Transitional Cell Carcinoma (TCC) of the bladder. The patient must have histologically-confirmed carcinoma in situ (CIS), with or without non-invasive papillary disease The patient must have immunohistochemically-confirmed EpCAM positive disease. The patient must have a life expectancy of at least 12 months. Prior/Concurrent Therapy The patient must have, within the last 24 months, failed to respond to at least 1 cycle of treatment with BCG (with or without interferon) or be intolerant to BCG treatment. The patient must have had a transurethral resection of the bladder tumour (TURBT) mapping the location of tumour and quantifying the area of bladder affected. The patient must have documented residual CIS (i.e. unresectable disease) prior to study drug administration. Patient Characteristics The patient must have adequate organ function, as defined by the clinical trial protocol Other The patient must have the ability to understand and sign an Independent Ethics Committee or Institutional Review Board (IEC/IRB)- approved informed consent document indicating that the patient (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrollment and is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. Exclusion Criteria: The patient has evidence of urethral or upper tract transitional cell carcinoma (TCC) by biopsy or upper tract radiological imaging (i.e. intravenous pyelogram, computed tomography (CT) urogram, or retrograde pyelogram) within the past 2 years The patient has hydronephrosis The patient has had prior intravesical chemotherapy or investigational or anti-cancer treatments within the last 2 months, inclusive of single-dose adjuvant intravesical chemotherapy immediately post-TURBT The patient has existing severe urinary tract infection or recurrent severe bacterial cystitis The patient has active, uncontrolled impairment of the renal, hepatobiliary, cardiovascular, gastrointestinal, urogenital, neurologic or hematopoietic systems which, in the opinion of the investigator, would predispose the patient to the development of complications from the administration of intravesical therapy and/or general anesthesia Any patient who, in the opinion of the investigator, cannot tolerate intravesical administration or intravesical surgical manipulation (cystoscopy, biopsy) due to the presence of concomitant serious illness (i.e. uncontrolled cardiac or respiratory disorders) The patient is pregnant or breast feeding Women of reproductive age (who are not either medically or surgically incapable or bearing children) and all men may not participate unless agreeing to use double barrier contraception, or commit to abstinence during the period of therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment Schedule A -<br>Induction Phase is a single intravesical dose of Vicinium at 30 mg in 40 mL PBS once per week for 6 weeks. If free of disease at 12 weeks after the first instillation, the subject enters Maintenance dosing in which 30 mg of Vicinium is administered once per week for 3 weeks followed by 9 weeks of no therapy. If the subject had histologically confirmed disease that is stage <T2, they repeat the Induction phase dosing. If the subject is free of disease, the subject enters the maintenance dosing phase of every 12 weeks (3 weeks of therapy followed by 9 weeks of no therapy until disease recurrence is confirmed by positive biopsy or up to a maximum of Week 51 (end-of-study [EOS]). | Drug: Vicinium<br>* Intravesical administration of Vicinium<br>* Other names: VB4-845;|
| Active Comparator: Treatment Schedule B<br>Induction Phase is a single intravesical dose of Vicinium at 30 mg in 40 mL PBS once per week for 12 weeks followed by 1 week of no therapy. If 13 weeks after the first instillation of Vicinium the subject is free of disease, they have a break from therapy before entering Maintenance dosing in which 30 mg of Vicinium is administered once weekly for 3 weeks followed by 9 weeks of no therapy. If the subject is free of disease, additional maintenance cycle(s) are repeated every 12 weeks (3 weeks of therapy followed by 9 weeks of no therapy until disease recurrence is confirmed by positive biopsy or up to a maximum of Week 57 (EOS). | Drug: Vicinium<br>* Intravesical administration of Vicinium<br>* Other names: VB4-845;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Schedule A: 12-Week Efficacy, Treatment Schedule B: 13-Week Efficacy | Complete response rate in subjects with carcinoma in situ (CIS) non-muscle invasive bladder cancer (NMIBC) following the induction phase (3-month evaluation point) of Vicinium treatment | 12 or 13 weeks |