A Phase 3 International, Double-Bind Trial Evaluating Efficacy and Safety of Multiple Instillations of Intravesical Apaziquone vs. Placebo in Patients With Low-Intermediate Risk Non-Muscle Invasive Bladder Cancer (NMIBC)

Inclusion Criteria

Inclusion Criteria (for Open Label):

1. Has the patient given written informed consent and is the patient willing and able to
abide by the protocol?

2. Is the patient 18 years old or above?

3. If the patient is a female of childbearing potential, is she using an
acceptable/effective method of contraception?

4. Does the female patient of childbearing potential have a negative serum pregnancy
test at screening?

5. Does the patient with clinically apparent primary or recurrent low grade Ta NMIBC
have :

- multiple tumors (2-7)

- No single Tumor > 3 cm

- No history / evidence of Tis

Or does the patient with clinically apparent primary or recurrent high grade Ta NMIBC
have:

- A single tumor that is ≤ 3 cm

- No history / evidence of Tis

6. Is the patient able to retain bladder instillations for a minimum of 60 minutes (± 6
minutes)?

7. Did the patient have upper urinary tract evaluation to exclude urothelial carcinoma,
hydronephrosis or renal cell carcinoma or other renal cancers in the 6 months prior
to study screening?

8. Is patient's urethra (including prostatic urethra in men) endoscopically free of any
visible TCC?

9. For patients with recurrent tumor, did the patient have at least a 6-month
cystoscopically-confirmed tumor-free interval between the last tumor recurrence and
the time of screening?

10. Has the male patient with a prostate specific antigen (PSA) between 4 and 10 ng/mL
had a diagnostic evaluation that reasonably excludes the diagnosis of prostate cancer
in the opinion of the Investigator?

Exclusion Criteria (for Open Label):

1. Has the patient received any previous pelvic radiotherapy (includes external beam
and/or brachytherapy)?

2. Has the patient ever received apaziquone?

3. Has the patient received an induction course (completed 5 of 6 scheduled weekly
instillations) of intravesical BCG (± interferon) with the last dose given less than
12 months ago?

4. Has the patient had any prior intravesical chemotherapy, exclusive of single-dose
adjuvant intravesical chemotherapy immediately post-TURBT?

5. Does the patient have a history of urinary retention or a post void residual ≥ 250 cc
by bladder scan or ultrasound (post void residual test may be repeated up to 3
times)?

6. Does the patient have or has the patient had any bladder tumor with histology other
than transitional cell carcinoma?

7. Does the patient have or has the patient had micro-papillary transitional cell
carcinoma?

8. If the patient has recurrent papillary disease of the bladder, has the pathology been
anything other than pTa in the past?

9. Does the patient have an active urinary tract infection confirmed by culture or a
documented history of recurrent UTI (≥ 6 for females and ≥2 for males per year) in
the prior 2 years?

10. Does the patient have a bleeding disorder or a screening platelet count < 50 x 109/L?

11. Does the patient have a screening hemoglobin < 10 g/dL?

12. Does the male patient have a screening serum PSA > 10 ng/mL?

13. Does the patient have a history of Acquired Immunodeficiency Syndrome or HIV
positive?

14. Does the patient have a condition or a concurrent severe and/or uncontrolled medical
or psychiatric disease (e.g., uncontrolled diabetes, decompensated congestive heart
failure, myocardial infarction within 6 months of study, unstable and uncontrolled
hypertension, or an active uncontrolled infection), which could compromise
participation, compliance with scheduled visits and/or completion of the study?

15. Has the patient participated in an investigational protocol within the past 90 days?

16. Is the patient pregnant or breast feeding?

17. Does the patient have a life expectancy of <3 years?

18. Has the patient had any other malignancy or received therapy for any malignancy in
the last five years except

- non-melanoma skin tumors

- stage 0 (in situ) cervical carcinoma

- undetectable PSA for ≥1 year following definitive therapy for localized prostate
cancer?

19. Does the patient have documented vesicoureteral reflux or an indwelling ureteral
stent?

20. Does the patient have tumor in a bladder diverticulum?

21. Does the patient have a known allergy to red color food dye?

Double-Blind Phase Inclusion Criteria

1. Was all visible tumor resected at the initial TURBT?

2. Does Central Pathology review of the patient's bladder tumor confirm:

- Low grade Ta disease for multiple tumors (2 - 7) or

- High Grade Ta disease for single tumor

- No microscopic evidence of lymphovascular invasion and/or evidence of tumor
thromboemboli