The purpose of this study is to explore a treatment that potentially enhances the delivery of chemotherapy to tumors in participants with superficial bladder cancer. The investigational medication to be studied is an enzyme called ChemophaseTM (recombinant human hyaluronidase, rHuPH20). Chemophase is being specifically developed for use with other anticancer drug to increase the local penetration of the anticancer drug for the treatment of superficial bladder cancer. In this study, Chemophase will be given in combination with mitomycin C directly into the bladder. Mitomycin C is an anti-tumor drug that is commonly used to treat superficial bladder cancer. It is envisioned that Chemophase with mitomycin C may potentially increase the local penetration of mitomycin C into remaining cancer cells following surgery to treat superficial bladder cancer.

The primary objectives of this study are to:

1. determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of escalating doses of Chemophase in combination with mitomycin (mitomycin C, MMC) administered as weekly intravesical instillations for five weeks, and
2. establish the dose of Chemophase with MMC recommended for future studies.

The secondary objectives of this study are to:

1. assess the pharmacokinetics of intravesical administration of MMC alone and in combination with intravesical administration of Chemophase,
2. for those participants treated at the MTD, assess the safety and tolerability of intravesical administration of MMC with Chemophase over up to 7 additional maintenance treatments every 3 months following the initial six weekly instillations, and
3. observe participants for any preliminary evidence of anti-tumor activity of MMC and Chemophase when combined.

Study participants will receive six weekly study treatments administered intravesically (at Weeks 1 through 6) followed by post-treatment evaluations, at Weeks 8 and 12. The 12 participants treated at MTD will continue to receive combination therapy every three months until the end of Year 2 or until the time of documented tumor recurrence, whichever occurs first. For other participants, long-term follow-up after Week 12 will consist of disease monitoring of participants by telephone and will be performed every three months beginning three months after last study treatment for two years and then every six months thereafter, until bladder tumor recurrence.

Inclusion Criteria:

• Participants with initial presentation or recurrence of Stage Ta, T1 or Tis, any grade, bladder cancer after transurethral resection of bladder tumor (TURBT).
• TURBT within 42 days prior to Day 1/Week 1
• Karnofsky Performance Status greater than or equal to 80%
• Life expectancy at least 3 years
• 18 years or older
• A negative pregnancy test (if female of child-bearing potential)
• Acceptable liver function within 7 days defined as: bilirubin less than or equal to 1.5 times upper limit of normal, and aspartate aminotransferase (AST) Glutamic-oxalacetic transaminase (SGOT), alanine aminotransferase (ALT), glutamic-pyruvic transaminase (SGPT), and alkaline phosphatase <= 2.5 times upper limit of normal
• Acceptable renal function within 7 days defined as: serum creatinine less than or equal to 1.5 times upper limit of normal, or calculated creatinine clearance greater than or equal to 40 milliliter (mL)/minute/1.73 meter^2
• Acceptable hematologic status within 7 days defined as: absolute neutrophil count (ANC) greater than or equal to 2,500 cells/millimeter^3, platelet count greater than or equal to 150,000/millileter^3, and hemoglobin greater than or equal to 10.0 grams/deciliter.
• 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 treatment period of the study.
• Signed, written Institutional Review Board (IRB)-approved informed consent

Exclusion Criteria:

• History or previous diagnosis of bladder fibrosis
• Total bladder capacity estimated at cystoscopy to be less than 150 mL
• Urinary incontinence of a severity that would compromise the ability of the participant to retain the study drug intravesical instillation for two hours.
• Severe irritative voiding symptoms such as urgency, frequency, or nocturia
• Known other malignant disease except squamous or basal cell skin cancer unless the malignancy has been in complete remission off therapy for at least 5 years.
• Major surgery, other than TURBT and diagnostic surgery, within 28 days prior to Day 1/Week 1.
• Active, uncontrolled bacterial, viral, or fungal infections, including urinary tract infection.
• Treatment with radiation therapy, surgery, chemotherapy, or investigational therapy within one month prior to Day 1/Week 1 on study (two months for nitrosureas 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 human immunodeficiency virus (HIV)
• Known active infection with hepatitis B or hepatitis C
• 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 a hypersensitivity or idiosyncratic reaction to, or other contraindication to, mitomycin.
• Known allergy to bee or vespid venom
• Known coagulation disorder or bleeding tendency
• Treatment with heparin or anticipation of heparin treatment during the treatment period in this study.
• Unwillingness or inability to comply with procedures required in this protocol.