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A Safety Study of Recombinant Human Hyaluronidase (Chemophase) in Combination With Mitomycin in Patients With Superficial Bladder Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00318643
Recruitment Status : Completed
First Posted : April 27, 2006
Last Update Posted : August 16, 2018
Sponsor:
Information provided by (Responsible Party):
Halozyme Therapeutics

Tracking Information
First Submitted Date  ICMJE April 25, 2006
First Posted Date  ICMJE April 27, 2006
Last Update Posted Date August 16, 2018
Study Start Date  ICMJE March 2006
Actual Primary Completion Date August 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 13, 2018)
  • 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 [ Time Frame: 5 weeks ]
  • Establish the dose of Chemophase with MMC recommended for future studies [ Time Frame: 6 weeks ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 25, 2006)
  • Determine the MTD and DLTs of escalating doses of Chemophase in combination with MMC administered weekly into the bladder for 5 weeks
  • Establish the dose of Chemophase with MMC recommended for future studies
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 13, 2018)
  • Pharmacokinetics (PKs) of MMC along and in combination with Chemophase [ Time Frame: Weeks 1, 2, 5, and 6: predose and 1, 2, and 3 hours postdose ]
  • Assess safety and tolerability of MMC with Chemophase over five instillations [ Time Frame: 12 weeks ]
  • For patients treated at the MTD, assess safety and tolerability of MMC with Chemophase over up to 7 additional treatments every 3 months following the initial 6 weekly treatments [ Time Frame: up to 2 years ]
  • Observe patients for any preliminary evidence of anti-tumor activity of MMC and Chemophase when combined [ Time Frame: up to 2 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 25, 2006)
  • PK of MMC along and in combination with Chemophase
  • Assess safety and tolerability of MMC with Chemophase over five instillations
  • For patients treated at the MTD, assess safety and tolerability of MMC with Chemophase over up to 7 additional treatments every 3 months following the initial 6 weekly treatments
  • Observe patients for any preliminary evidence of anti-tumor activity of MMC and Chemophase when combined
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Safety Study of Recombinant Human Hyaluronidase (Chemophase) in Combination With Mitomycin in Patients With Superficial Bladder Cancer
Official Title  ICMJE 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
Brief Summary The purpose of this study is to explore other treatments for patients with superficial bladder cancer. The investigational medication to be studied is an enzyme called hyaluronidase, and it is a human recombinant form of the enzyme. An investigational medication is a medication or formulation of a medication that is not approved by the United States Food and Drug Administration for use in this country but it may be used in studies such as this one. The drug company name for this medication is Chemophase. Chemophase will be given in combination with mitomycin C. Mitomycin C will be given alone one time and then both drugs will be given together weekly for 5 weeks. Mitomycin C is an anti-tumor drug that is commonly used to treat superficial bladder cancer. Treatments are administered directly into the bladder. 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.
Detailed Description

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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Bladder Cancer
Intervention  ICMJE
  • Drug: Mitomycin C
    intravesical administration
  • Drug: Chemophase
    intravesical administration
Study Arms  ICMJE
  • Experimental: Cohort 1: MMC plus Chemophase
    On Day 1 of Week 1, all participants will receive mitomycin C (MMC) 40 milligrams (mg)/20 milliliter (mL) monotherapy via intravesical administration. In Weeks 2 through 6, participants will receive weekly intravesical administrations of a combination of MMC 40 mg/20 mL and 20,000 Units Chemophase.
    Interventions:
    • Drug: Mitomycin C
    • Drug: Chemophase
  • Experimental: Cohort 2: MMC plus Chemophase
    On Day 1 of Week 1, all participants will receive MMC 40 mg/20 mL monotherapy via intravesical administration. In Weeks 2 through 6, participants will receive weekly intravesical administrations of a combination of MMC 40 mg/20 mL and 60,000 Units Chemophase.
    Interventions:
    • Drug: Mitomycin C
    • Drug: Chemophase
  • Experimental: Cohort 3: MMC plus Chemophase
    On Day 1 of Week 1, all participants will receive MMC 40 mg/20 mL monotherapy via intravesical administration. In Weeks 2 through 6, participants will receive weekly intravesical administrations of a combination of MMC 40 mg/20 mL and 200,000 Units Chemophase.
    Interventions:
    • Drug: Mitomycin C
    • Drug: Chemophase
  • Experimental: Cohort 4: MMC plus Chemophase
    On Day 1 of Week 1, all participants will receive MMC 40 mg/20 mL monotherapy via intravesical administration. In Weeks 2 through 6, participants will receive weekly intravesical administrations of a combination of MMC 40 mg/20 mL and 400,000 Units Chemophase.
    Interventions:
    • Drug: Mitomycin C
    • Drug: Chemophase
  • Experimental: Cohort 5: MMC plus Chemophase
    On Day 1 of Week 1, all participants will receive MMC 40 mg/20 mL monotherapy via intravesical administration. In Weeks 2 through 6, participants will receive weekly intravesical administrations of a combination of MMC 40 mg/20 mL and 800,000 Units Chemophase.
    Interventions:
    • Drug: Mitomycin C
    • Drug: Chemophase
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 3, 2008)
27
Original Enrollment  ICMJE
 (submitted: April 25, 2006)
36
Actual Study Completion Date  ICMJE August 2010
Actual Primary Completion Date August 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00318643
Other Study ID Numbers  ICMJE HZ2-05-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Halozyme Therapeutics
Study Sponsor  ICMJE Halozyme Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Halozyme Therapeutics
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP