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)
Overview
- Phase
- Phase 3
- Intervention
- Apaziquone
- Conditions
- Bladder Cancer
- Sponsor
- Spectrum Pharmaceuticals, Inc
- Enrollment
- 802
- Locations
- 72
- Primary Endpoint
- Recurrence Rate at 2 Years
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
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
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.
Investigators
Eligibility Criteria
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?
Arms & Interventions
Apaziquone
TURBT + a single intravesical dose of Apaziquone 4mg in 40ml instilled into the bladder post-TURBT
Intervention: Apaziquone
Apaziquone
TURBT + a single intravesical dose of Apaziquone 4mg in 40ml instilled into the bladder post-TURBT
Intervention: TURBT
Placebo
TURBT + a single intravesical dose of placebo instilled into the bladder post-TURBT
Intervention: Placebo
Placebo
TURBT + a single intravesical dose of placebo instilled into the bladder post-TURBT
Intervention: TURBT
Outcomes
Primary Outcomes
Recurrence Rate at 2 Years
Time Frame: 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.
Secondary Outcomes
- Time to Progression(2 years)
- Time to Recurrence(2 years)
- Progression Rate at 2 Years(2 years)
- Number of Recurrences Per Patient(2 years)
- Disease Free Interval(2 years)
- Disease Free Survival(2 years)
- Overall Survival(2 years)