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A Phase I-IIa, Multicenter, Open-Label, Multiple Dose, Safety, Tolerability and Pharmacokinetic Study of Recombinant Human Hyaluronidase (Chemophase) in Combination With Mitomycin in Patients With Non-Muscular-Invasive Bladder Cancer


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Bladder Cancer

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Trial Information

A Phase I-IIa, Multicenter, Open-Label, Multiple Dose, Safety, Tolerability and Pharmacokinetic Study of Recombinant Human Hyaluronidase (Chemophase) in Combination With Mitomycin in Patients With Non-Muscular-Invasive 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 patients 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 patients for any preliminary evidence of anti-tumor activity of MMC and
Chemophase when combined.

Study patients will receive six (6) weekly study treatments (at Weeks 1 through 6) followed
by post-treatment evaluations, at Weeks 8 and 12. The 12 patients 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 patients,
long-term follow-up after Week 12 will consist of disease monitoring of patients by
telephone and will be performed every three (3) months beginning three months after last
study treatment for two years and then every six (6) months thereafter, until bladder tumor
recurrence.

The following therapies are prohibited from the time of enrollment through Week 12 of the
study:

- Treatment with heparin

- Any intravesical therapy except for MMC and Chemophase

- Any potentially myelosuppressive therapy

For the MTD patients who are receiving continued study drug treatments after Week 12, the
following therapies are prohibited for the duration of study drug treatment:

- Any intravesical therapy except for MMC and Chemophase

- Any potentially myelosuppressive therapy


Inclusion Criteria:



- Patients 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 AST (SGOT), ALT (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 mL/min/1.73 m2

- Acceptable hematologic status within 7 days defined as: absolute neutrophil count
(ANC) greater than or equal to 2,500 cells/mm3, platelet count greater than or equal
to 150,000/mm3, and hemoglobin greater than or equal to 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 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 patient
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 (1) month prior to Day 1/Week 1 on study (two [2] 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.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Outcome Measure:

Determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of escalating doses of Chemophase in combination with mitomycin C (MMC) administered weekly into the bladder for 5 weeks

Authority:

United States: Food and Drug Administration

Study ID:

HZ2-05-01

NCT ID:

NCT00318643

Start Date:

March 2006

Completion Date:

Related Keywords:

  • Bladder Cancer
  • Non-invasive bladder cancer
  • Chemophase
  • Intravesical administration
  • Superficial Bladder Cancer
  • Urinary Bladder Neoplasms

Name

Location

Advanced Research InstituteNew Port Richey, Florida  34652
James A. Haley Veterans HospitalTampa, Florida  33612
BCG OncologyPhoenix, Arizona  85032
MedResearchLa Mesa, California  91942
Malcolm Randall Veterans Administration Urology Section (112-C)Gainsville, Florida  32608