Study of Immediate Post-Operative Intravesical Instillation of Chemophase® in Patients With Superficial Bladder Cancer (IPOP)

This study has been completed.
Sponsor:
Information provided by:
Halozyme Therapeutics
ClinicalTrials.gov Identifier:
NCT00782587
First received: October 29, 2008
Last updated: February 5, 2010
Last verified: February 2010
  Purpose

The purpose of this research study is to test the safety and tolerability of an experimental drug, Chemophase, a combination of recombinant human hyaluronidase, (an investigational synthetic enzyme also known as rHuPH20), and mitomycin (MMC) in the treatment of superficial bladder cancer when instilled intravesically immediately after TURBT (transurethral resection of bladder tumor).


Condition Intervention Phase
Superficial Bladder Cancer
Drug: Chemophase
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Halozyme Therapeutics:

Primary Outcome Measures:
  • Safety and Tolerability of immediate post-operative instillation of Chemophase. [ Time Frame: Day 1 instillation, and weeks 1, 2, and 12 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Assess plasma levels of mitomycin (MMC) after IPOP intravesical instillation. [ Time Frame: Hours 1, 2 and 3 post-instillation ] [ Designated as safety issue: Yes ]

Enrollment: 14
Study Start Date: October 2008
Study Completion Date: August 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
Single arm, open label, single dose, intravesical instillation of Chemophase (combination of rHuPH20 and mitomycin) for appropriate superficial bladder cancer patients within 6 hours of TURBT.
Drug: Chemophase
40 mg mitomycin with 800,000 U rHuPH20 total volume of 40 mL instilled
Other Name: Chemophase

Detailed Description:

Patients will be screened and enrolled prior to undergoing standard of care TURBT for known or suspected Stage Ta, T1 or Tis bladder cancer of any histological grade requiring TURBT and who are believed to be candidates for IPOP intravesical chemotherapy regardless of the need for further intravesical therapy. Within 6 hours after completion of TURBT, patients will be administered a single IPOP intravesical instillation of Chemophase with a one-hour dwell time. At the end of the one-hour dwell time, the patient will be asked to fully void or, if an intravesical catheter has been left in place, the bladder will be fully drained via the catheter. Patients will return at 1 and 2 weeks post instillation for follow up visits for safety and for a cystoscopy at day 85 (per standard of care). Safety and tolerability will be assessed through physical examinations, vital signs, cystoscopy, hematology (CBC), adverse event reporting, and measurements of plasma levels of MMC.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00782587

Locations
United States, Arizona
BCG Oncology, PC
Phoenix, Arizona, United States, 85032
United States, California
Advanced Urology Medical Center
Anaheim, California, United States, 92801
Medresearch
La Mesa, California, United States, 91942
United States, Florida
Malcolm Randall Veterans Administration
Gainesville, Florida, United States, 32608
Advanced Research Institute, Inc.
New Port Richey, Florida, United States, 34655
Sponsors and Collaborators
Halozyme Therapeutics
Investigators
Principal Investigator: Donald Lamm, M.D. BCG Oncology, PC
  More Information

No publications provided

Responsible Party: Jonathan Leff, M.D., Halozyme Therapeutics
ClinicalTrials.gov Identifier: NCT00782587     History of Changes
Other Study ID Numbers: HZ2-08-01
Study First Received: October 29, 2008
Last Updated: February 5, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Halozyme Therapeutics:
Non-Muscle-Invasive Bladder Cancer
Superficial Bladder Cancer
recombinant human hyaluronidase
rHuPH20
Chemophase®
Mitomycin

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Mitomycins
Mitomycin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Alkylating Agents

ClinicalTrials.gov processed this record on April 17, 2014