Phase I Safety and Tolerability Study of Immediate Post-Operative Intravesical Instillation of Chemophase® (Recombinant Human Hyaluronidase in Combination With Mitomycin) in Patients With Non-Muscle-Invasive Bladder Cancer

Inclusion Criteria:

- Patient with histologically confirmed or suspected (based on cystoscopy) initial
presentation or recurrence of Stage Ta, T1, or Tis transitional cell bladder cancer
of any histological grade requiring TURBT.

- Patient believed to be a candidate for immediate post-operative chemotherapy
regardless of the need for additional intravesical therapy.

- ECOG performance status of Grade 0 or 1.

- Age ≥ 18 years.

- A negative urine or serum pregnancy test (if female of child-bearing potential)
within 14 days prior to Day 1/Week 1.

- Acceptable liver function within 14 days prior to Day 1/Week 1 defined as:

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN), and

- AST (SGOT), ALT (SGPT), and alkaline phosphatase ≤ 2.5 times ULN.

- Acceptable renal function within 14 days prior to Day 1/Week 1 defined as serum
creatinine ≤ 1.5 x ULN.

- Acceptable hematologic status within 14 days prior to Day 1/Week 1 defined as:

- Absolute neutrophil count (ANC) ≥ 1,500/dL,

- Platelet count ≥ 100,000/dL, and

- Hemoglobin ≥ 10.0 g/dL.

- Urinalysis showing no clinically significant abnormalities, except those attributable
to bladder cancer.

- For men and women of child-producing potential, agreement to use an effective
contraceptive method during the study from enrollment until 2 weeks after the
administration of study drug.

- Signed, written, IRB-approved informed consent.

Exclusion Criteria:

- Large resected area (estimated total area > 50 cm²) or suspected deep resection, even
in the absence of signs of perforation beyond the muscularis propria or ongoing
significant bleeding.

- Known or suspected bladder perforation during TURBT.

- Failure to completely resect all cancerous lesions or suspected presence of
muscle-invasive cancer (Stage T2 or higher).

- Previous diagnosis or current presence of bladder fibrosis/contracture, or total
bladder capacity estimated at cystoscopy or by other means to be < 150 mL.

- Urinary incontinence or severe irritative voiding symptoms such as urgency,
frequency, or nocturia of a severity that would compromise the ability of the patient
to retain the study drug intravesical instillation for one hour.

- Bladder cancer recurrence less than 3 months after a previous TURBT.

- Major surgery, other than TURBT or diagnostic surgery, within 28 days prior to Day
1/Week 1.

- Known active, uncontrolled bacterial, viral, or fungal infections, including urinary
tract infection.

- Any intravesical therapy within 3 months prior to Week 1/Day 1.

- Systemic therapy including radiation therapy, surgery, chemotherapy, or
investigational therapy within one month prior to Day 1/Week 1 (two months for
nitrosoureas or MMC), unless given as standard treatment for bladder cancer and
provided that patient is free of all treatment-related toxicities as of Day 1/Week 1.

- Known infection with HIV.

- Known active infection with hepatitis B or hepatitis C virus.

- Serious disease (e.g., hydronephrosis, liver failure, or other conditions) that could
compromise protocol objectives in the opinion of the Investigator and/or the Sponsor
(Halozyme).

- History of hypersensitivity or idiosyncratic reaction to, or other contraindication
to, MMC.

- Known allergy to bee or vespid venom.

- Known coagulation disorder or bleeding tendency.

- Ongoing treatment with heparin or other anticoagulation therapy, or anticipation of
such therapy during the treatment period in this study.

- Unwillingness or inability to comply with procedures required in this protocol.