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

NCT00318643 | Completed Phase 1 Results

• 1 other identifier: HZ2-05-01
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 5

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.

Conditions

Bladder Cancer

Keywords

Non-invasive bladder cancer; Chemophase; Intravesical administration; Superficial Bladder Cancer

Outcome Measures

Primary Outcomes (3)

• 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.

  5 weeks (Week 2 to Week 6)

• 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.

  5 weeks (Week 2 to Week 6)

• Recommended Dose of Chemophase With MMC For Future Studies

  5 weeks (Week 2 to Week 6)

Secondary Outcomes (3)

• Number of Participants With a Quantifiable MMC Plasma Concentration Value

  0 (predose), 1, 2, and 3 hours postdose at Weeks 1, 2, 5, and 6

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  Baseline up to 2 years

• Number of Participants Who Remained Tumor Free at the End of the Study

  Baseline up to 2 years

Study Arms (5)

Cohort 1: MMC plus Chemophase 20,000 U

EXPERIMENTAL

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.

Drug: Mitomycin C; Drug: Chemophase

Cohort 2: MMC plus Chemophase 60,000 U

EXPERIMENTAL

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.

Drug: Mitomycin C; Drug: Chemophase

Cohort 3: MMC plus Chemophase 200,000 U

EXPERIMENTAL

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.

Drug: Mitomycin C; Drug: Chemophase

Cohort 4: MMC plus Chemophase 400,000 U

EXPERIMENTAL

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.

Drug: Mitomycin C; Drug: Chemophase

Cohort 5: MMC plus Chemophase 800,000 U

EXPERIMENTAL

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.

Drug: Mitomycin C; Drug: Chemophase

Interventions

Mitomycin C DRUG

intravesical administration

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

Chemophase DRUG

intravesical administration

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Halozyme Therapeutics: lead

Study Sites (5)

BCG Oncology

Phoenix, Arizona, 85032, United States

Location

MedResearch

La Mesa, California, 91942, United States

Location

Malcolm Randall Veterans Administration Urology Section (112-C)

Gainesville, Florida, 32608, United States

Location

Advanced Research Institute

New Port Richey, Florida, 34652, United States

Location

James A. Haley Veterans Hospital

Tampa, Florida, 33612, United States

Location

Related Links

• Sponsor's website

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Non-Muscle Invasive Bladder Neoplasms

Interventions

Mitomycin

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Mitomycins; Indolequinones; Quinones; Organic Chemicals; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Halozyme Therapeutics

halozyme@EVERSANA.com

855-495-3639

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2006
• First Posted: April 27, 2006
• Study Start: March 30, 2006
• Primary Completion: August 11, 2009
• Study Completion: August 11, 2009
• Last Updated: October 29, 2021
• Results First Posted: October 29, 2021

Record last verified: 2021-09

Locations

US (5)