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

Primary Purpose

Bladder Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Mitomycin C
Chemophase
Sponsored by
Halozyme Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Bladder Cancer focused on measuring Non-invasive bladder cancer, Chemophase, Intravesical administration, Superficial Bladder Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • BCG Oncology
  • MedResearch
  • Malcolm Randall Veterans Administration Urology Section (112-C)
  • Advanced Research Institute
  • James A. Haley Veterans Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort 1: MMC plus Chemophase 20,000 U

Cohort 2: MMC plus Chemophase 60,000 U

Cohort 3: MMC plus Chemophase 200,000 U

Cohort 4: MMC plus Chemophase 400,000 U

Cohort 5: MMC plus Chemophase 800,000 U

Arm Description

Participants will receive 40 milligrams (mg) MMC intravesically on Day 1 of Week 1 followed by a combination of 40 mg MMC and 20,000 U Chemophase intravesically once weekly from Weeks 2 through 6.

Participants will receive 40 mg MMC intravesically on Day 1 of Week 1 followed by a combination of 40 mg MMC and 60,000 U Chemophase intravesically once weekly from Weeks 2 through 6.

Participants will receive 40 mg MMC intravesically on Day 1 of Week 1 followed by a combination of 40 mg MMC and 200,000 U Chemophase intravesically once weekly from Weeks 2 through 6.

Participants will receive 40 mg MMC intravesically on Day 1 of Week 1 followed by a combination of 40 mg MMC and 400,000 U Chemophase intravesically once weekly from Weeks 2 through 6.

Participants will receive 40 mg MMC intravesically on Day 1 of Week 1 followed by a combination of 40 mg MMC and 800,000 U Chemophase intravesically once weekly from Weeks 2 through 6.

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose (MTD) of Chemophase in Combination With MMC
The MTD was defined as the maximum dose level at which no more than two of six participants experienced dose-limiting toxicities (DLT). DLT was defined as any of the following: Plasma MMC concentration greater than or equal to (>=) 100 nanograms (ng)/milliliter (mL) Adverse event (AE) with a Common Toxicity Criteria (CTC) grade greater than or equal to 3 New, treatment-emergent diagnosis of bladder fibrosis.
Number of Participants With Dose Limiting Toxicities (DLTs)
DLT was defined as any of the following: Plasma MMC concentration >= 100 ng/mL AE with a CTC grade greater than or equal to 3 New, treatment-emergent diagnosis of bladder fibrosis.
Recommended Dose of Chemophase With MMC For Future Studies

Secondary Outcome Measures

Number of Participants With a Quantifiable MMC Plasma Concentration Value
A quantifiable MMC plasma concentration value was a value that was not below the quantifiable limit (BQL) of <10.0 nanogram/milliliter (ng/mL).
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
TEAEs were defined as any AE that occurred after the first administration of the study drug and until the end of the study. AEs were defined as any untoward medical occurrence in a participant administered study drug and that did not necessarily have a causal relationship with the study drug. SAEs were defined as any AE that, in the view of either the Investigator or Sponsor, resulted in any of the following outcomes as fatal, life-threatening, required in-participant hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, an important medical event. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in 'Reported Adverse Events' Section.
Number of Participants Who Remained Tumor Free at the End of the Study

Full Information

First Posted
April 25, 2006
Last Updated
September 30, 2021
Sponsor
Halozyme Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT00318643
Brief Title
Safety Study of Recombinant Human Hyaluronidase (Chemophase) in Combination With Mitomycin in Participants With Superficial Bladder Cancer
Official Title
A Phase 1-2a, 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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
March 30, 2006 (Actual)
Primary Completion Date
August 11, 2009 (Actual)
Study Completion Date
August 11, 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Halozyme Therapeutics

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
Detailed Description
The primary objectives of this study are to: 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 establish the dose of Chemophase with MMC recommended for future studies. The secondary objectives of this study are to: assess the pharmacokinetics of intravesical administration of MMC alone and in combination with intravesical administration of Chemophase, 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bladder Cancer
Keywords
Non-invasive bladder cancer, Chemophase, Intravesical administration, Superficial Bladder Cancer

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1: MMC plus Chemophase 20,000 U
Arm Type
Experimental
Arm Description
Participants will receive 40 milligrams (mg) MMC intravesically on Day 1 of Week 1 followed by a combination of 40 mg MMC and 20,000 U Chemophase intravesically once weekly from Weeks 2 through 6.
Arm Title
Cohort 2: MMC plus Chemophase 60,000 U
Arm Type
Experimental
Arm Description
Participants will receive 40 mg MMC intravesically on Day 1 of Week 1 followed by a combination of 40 mg MMC and 60,000 U Chemophase intravesically once weekly from Weeks 2 through 6.
Arm Title
Cohort 3: MMC plus Chemophase 200,000 U
Arm Type
Experimental
Arm Description
Participants will receive 40 mg MMC intravesically on Day 1 of Week 1 followed by a combination of 40 mg MMC and 200,000 U Chemophase intravesically once weekly from Weeks 2 through 6.
Arm Title
Cohort 4: MMC plus Chemophase 400,000 U
Arm Type
Experimental
Arm Description
Participants will receive 40 mg MMC intravesically on Day 1 of Week 1 followed by a combination of 40 mg MMC and 400,000 U Chemophase intravesically once weekly from Weeks 2 through 6.
Arm Title
Cohort 5: MMC plus Chemophase 800,000 U
Arm Type
Experimental
Arm Description
Participants will receive 40 mg MMC intravesically on Day 1 of Week 1 followed by a combination of 40 mg MMC and 800,000 U Chemophase intravesically once weekly from Weeks 2 through 6.
Intervention Type
Drug
Intervention Name(s)
Mitomycin C
Intervention Description
intravesical administration
Intervention Type
Drug
Intervention Name(s)
Chemophase
Intervention Description
intravesical administration
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose (MTD) of Chemophase in Combination With MMC
Description
The MTD was defined as the maximum dose level at which no more than two of six participants experienced dose-limiting toxicities (DLT). DLT was defined as any of the following: Plasma MMC concentration greater than or equal to (>=) 100 nanograms (ng)/milliliter (mL) Adverse event (AE) with a Common Toxicity Criteria (CTC) grade greater than or equal to 3 New, treatment-emergent diagnosis of bladder fibrosis.
Time Frame
5 weeks (Week 2 to Week 6)
Title
Number of Participants With Dose Limiting Toxicities (DLTs)
Description
DLT was defined as any of the following: Plasma MMC concentration >= 100 ng/mL AE with a CTC grade greater than or equal to 3 New, treatment-emergent diagnosis of bladder fibrosis.
Time Frame
5 weeks (Week 2 to Week 6)
Title
Recommended Dose of Chemophase With MMC For Future Studies
Time Frame
5 weeks (Week 2 to Week 6)
Secondary Outcome Measure Information:
Title
Number of Participants With a Quantifiable MMC Plasma Concentration Value
Description
A quantifiable MMC plasma concentration value was a value that was not below the quantifiable limit (BQL) of <10.0 nanogram/milliliter (ng/mL).
Time Frame
0 (predose), 1, 2, and 3 hours postdose at Weeks 1, 2, 5, and 6
Title
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Description
TEAEs were defined as any AE that occurred after the first administration of the study drug and until the end of the study. AEs were defined as any untoward medical occurrence in a participant administered study drug and that did not necessarily have a causal relationship with the study drug. SAEs were defined as any AE that, in the view of either the Investigator or Sponsor, resulted in any of the following outcomes as fatal, life-threatening, required in-participant hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, an important medical event. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in 'Reported Adverse Events' Section.
Time Frame
Baseline up to 2 years
Title
Number of Participants Who Remained Tumor Free at the End of the Study
Time Frame
Baseline up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
BCG Oncology
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85032
Country
United States
Facility Name
MedResearch
City
La Mesa
State/Province
California
ZIP/Postal Code
91942
Country
United States
Facility Name
Malcolm Randall Veterans Administration Urology Section (112-C)
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32608
Country
United States
Facility Name
Advanced Research Institute
City
New Port Richey
State/Province
Florida
ZIP/Postal Code
34652
Country
United States
Facility Name
James A. Haley Veterans Hospital
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.halozyme.com
Description
Sponsor's website

Learn more about this trial

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

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