Single Dose Intravesical Apaziquone Postoperative in Patients Undergoing TURBT for Noninvasive Bladder Cancer (SPI-612)

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-612)

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.

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 of the following questions must be answered "Yes" in order for the patient to participate in the study.

1. Has the patient given written informed consent?
2. Is the patient at least 18 years old?
3. Does the patient have transitional cell carcinoma of the bladder with clinically apparent tumor Ta, grade G1-G2?
4. If the patient is a female of childbearing potential, is she using an acceptable/effective method of contraception?
5. If the patient is a female of childbearing potential, has she had a negative serum pregnancy test within the past 14 days?
6. Is the patient willing and able to abide by the protocol?

Exclusion Criteria:

All of the following questions must be answered "No" in order for the patient to participate in the study.

1. Does the patient have more than 5 bladder tumors?
2. Does any single bladder tumor exceed 3.5 cm in diameter?
3. Does the patient have a single, primary bladder tumor <0.5 cm and has no previous diagnosis of bladder cancer?
4. Has the patient ever received EOquin(r)?
5. Does the patient have, or has the patient ever had, any bladder tumor known to be other than tumor Ta or grade G1 or G2 (low grade [WHO/ISUP classification])?
6. Does the patient have, or has the patient ever had any bladder tumor with histology other than transitional cell carcinoma?
7. Does the patient have, or has the patient ever had, carcinoma in situ (CIS)?
8. Does the patient have an active urinary tract infection?
9. Does the patient have a bleeding disorder or a screening platelet count < 100 x 109/L?
10. Does the patient have any unstable medical condition that would make it unsafe for him/her to undergo TURBT under general or spinal anesthesia?
11. Does the patient have screening hemoglobin < 10 mg/dL, a screening absolute neutrophil count < 1.5 x 109/L?
12. Does the patient have a known immunodeficiency disorder?
13. Has the patient received any investigational treatment within the past 30 days?
14. Is the patient breast feeding?
15. Does the patient have a history of interstitial cystitis?
16. Does the patient have a history of allergy to red color food dye?
17. Has the patient had transitional cell carcinoma of the bladder within the past 4 months?