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.
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 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 3. 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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
27
intravesical administration
intravesical administration
BCG Oncology
Phoenix, Arizona, United States
MedResearch
La Mesa, California, United States
Malcolm Randall Veterans Administration Urology Section (112-C)
Gainesville, Florida, United States
Advanced Research Institute
New Port Richey, Florida, United States
James A. Haley Veterans Hospital
Tampa, Florida, United States
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.
Time frame: 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.
Time frame: 5 weeks (Week 2 to Week 6)
Recommended Dose of Chemophase With MMC For Future Studies
Time frame: 5 weeks (Week 2 to Week 6)
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).
Time frame: 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)
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
Number of Participants Who Remained Tumor Free at the End of the Study
Time frame: Baseline up to 2 years
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