Single Dose Intravesical Apaziquone Postoperative in Patients Undergoing TURBT for Noninvasive Bladder Cancer (SPI-611)

Study Overview
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Brief Summary
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The purpose of this study was to evaluate the 2-Year Recurrence Rate of bladder cancer in randomized patients with tumor histology Ta, G1-G2 who received TransUrethral Resection of Bladder Tumor (TURBT) plus apaziquone versus those who received TURBT plus placebo.

Detailed Description
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This was a Phase 3, multicenter, randomized, double-blind, placebo-controlled study. Within 14 days of Screening, eligible patients underwent a TURBT during Visit 1 (Day 0) following which they were immediately randomized in a 1:1 ratio to receive either placebo or 4 mg apaziquone, instilled in a volume of 40 mL into the bladder within 6 hours from the end of the TURBT procedure. After a 60-minute retention period, study drug was drained from the bladder. A postoperative follow-up examination and review of the local pathology report were performed at Visit 2, which occurred 21 days (±10 days) after the TURBT (Week 3). If the histology of the patient's tumor was confirmed as Ta, G1-G2 (ie, low grade according to World Health Organization [WHO]/International Society of Urologic Pathology [ISUP] classification), no further treatment was given and the patient was observed cystoscopically every 3 months through Year 2 for tumor recurrence (Visit 3 through Visit 10). If the histology of the patient's tumor was other than Ta, G1 or G2 (low grade [WHO/ISUP classification]), further treatment was given in accordance with current treatment guidelines, and the patient was followed up cystoscopically every 3 months through Year 2 for tumor recurrence (Visit 3 through Visit 10). All patients were to be followed for 2 years.

Official Title
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A Multicenter, Randomized, Placebo-Controlled, Double-Blind, Phase 3 Trial of Single Dose Intravesical Apaziquone (EOquin®) as a Surgical Adjuvant Instilled in the Early Postoperative Period in Patients Undergoing Transurethral Resection for Noninvasive Bladder Cancer (Protocol SPI-611)

Conditions
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Bladder Cancer

Intervention / Treatment
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* Drug: Apaziquone
* Drug: Placebo
* Procedure: TURBT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (All questions must be answered YES) Has the patient given written informed consent? Is the patient at least 18 years old? Does the patient have transitional cell carcinoma of the bladder with clinically apparent stage Ta, grade G1-G2? If the patient is a female of childbearing potential, is she using an acceptable/effective method of contraception? If the patient is a female of childbearing potential, has she had a negative serum pregnancy test within the past 14 days? Is the patient willing and able to abide by the protocol? Exclusion Criteria: (All questions must be answered NO) Does the patient have more than 4 bladder tumors? Does any single bladder tumor exceed 3.5 cm in diameter? Does the patient have a single, primary (no previous diagnosis of TCC) bladder tumor <0.5 cm? Has the patient ever received Apaziquone? Does the patient have, or has the patient ever had, any bladder tumor known to be other than stage Ta or grade G1 or G2 (low grade [WHO/ISUP classification])? Does the patient have, or has the patient ever had any bladder tumor with histology other than transitional cell carcinoma? Does the patient have, or has the patient ever had, carcinoma in situ (CIS)? Does the patient have an active urinary tract infection? Does the patient have a bleeding disorder or a screening platelet count < 100 x 10^9/L? Does the patient have any unstable medical condition that would make it unsafe for him/her to undergo TURBT under general or spinal anesthesia? Does the patient have a screening hemoglobin < 10 mg/dL, a screening absolute neutrophil count < 1.5 x 10^9/L or a screening creatinine > 2 mg/dL? Does the patient have a known immunodeficiency disorder? Has the patient received any investigational treatment within the past 30 days? Is the patient breast feeding? Does the patient have a history of interstitial cystitis? Does the patient have a history of allergy to red color food dye? Has the patient had transitional cell carcinoma of the bladder within the past 4 months?

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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apaziquone<br>TURBT + a single intravesical dose of Apaziquone 4mg in 40ml instilled into the bladder post-TURBT | Drug: Apaziquone<br>* A single intravesical dose of Apaziquone 4mg in 40ml instilled into the bladder post-TURBT<br>* Other names: EOquin®, Qapzola;Procedure: TURBT<br>* TransUrethral Resection of the Bladder Tumor<br>|
| Placebo Comparator: Placebo<br>TURBT + a single intravesical dose of placebo instilled into the bladder post-TURBT | Drug: Placebo<br>* A single intravesical dose of placebo instilled into the bladder post-TURBT<br>Procedure: TURBT<br>* TransUrethral Resection of the Bladder Tumor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence Rate at 2 Years | The percentage of participants with histologically confirmed recurrence of the bladder tumor at any time after randomization and on or before year 2. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Recurrence | The number of months from randomization to histologically confirmed recurrence of the patient's bladder tumor. | 2 years | 
| Progression Rate at 2 Years | The percentage of participants that progress to either a higher stage or grade from the histologically confirmed stage and grade at time of randomization. | 2 years | 
| Time to Progression | The number of months from randomization to progression to either a higher stage or grade of the patient's bladder tumor. | 2 years | 
| Number of Recurrences Per Patient | The number of histologically confirmed recurrences during the course of the study. | 2 years | 
| Disease Free Interval | The number of months from randomization to histologically confirmed progression of the patient's bladder tumor or death from any cause | 2 years | 
| Disease Free Survival | The number of months from randomization to histologically confirmed recurrence of the patient's bladder tumor or death from any cause | 2 years | 
| Overall Survival | The number of months from randomization to death from any cause. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Noninvasive Bladder Cancer