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

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.

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?