This study will evaluate the safety and efficacy of intravesical administration of detalimogene (EG-70) in the bladder and its effect on bladder tumors in patients with NMIBC. This study study consists of two phases; a Phase 1 dose-escalation to establish safety and recommended the phase 2 dose, followed by a Phase 2 study to establish how effective the treatment is. The Study will include patients with: NMIBC with CIS for whom BCG therapy is unresponsive, and other high risk patients with NMIBC. A Substudy will include a surfactant bladder rinse prior to the instillation of detalimogene in patients with NMIBC with CIS for whom BCG therapy is unresponsive.
EG-70 is a novel non-viral gene therapy. EG-70 is designed to elicit a local immune response following delivery of the study gene therapy to the bladder urothelium. This approach of local administration through bladder instillation has the potential to induce a potent immune response exclusively at the site of the tumor, resulting in greater therapeutic benefit while reducing undesirable systemic toxicity. Eligible BCG-unresponsive NMIBC with CIS patients will be enrolled in Phase 1, and Cohort 1 of Phase 2. Eligible high-risk NMIBC patients will be enrolled in Phase 2 into separate cohorts include: BCG-naïve patients or BCG-exposed (incompletely treated) patients with Carcinoma in situ (CIS), and BCG-unresponsive HG Ta/T1 papillary disease without CIS. Patients will be treated for up to four 12-week cycles of study drug instillation doses and assessments with follow up assessments. Patients with complete response following four treatment cycles will enter up to 8 maintenance treatment cycles.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
350
Patients will receive up to four cycles of EG-70 administered as a bladder instillation of a 50 mL volume of study drug via catheter with a targeted retention time of 60 minutes.One cycle lasts approximately 12 weeks and consists of either a 2-dose (Day 1 and Day 8) or 4-dose (Day 1, Day 8, Day 29 and Day 36) regimen.
Under the Treatment Period, patients will receive 4 instillations per cycle for up to 4 cycles, of EG-70 at the RP2D defined in Phase 1, administered as a bladder instillation of a 50 mL volume of study drug via catheter with a targeted retention time of 60 minutes. One cycle lasts approximately 12 weeks. For Maintenance treatment 2 doses of EG-70 will be administered as a bladder instillation per 12-week cycle.
Patients will receive via catheter a 50 mL volume of a 5-minute bladder rinse immediately prior to administration of 50 mL of detalimogene voraplasmid (EG-70) at the RP2D for 30 minutes. During the Treatment Period, patients will receive 4 instillations per cycle for up to 4 cycles of the sudy intervention. One cycle lasts approximately 12 weeks. For Maintenance treatment, 2 doses of the study intervention will be administered as a bladder instillation per 12-week cycle.
The University of Alabama at Birmingham Clinical Research Unit (CRU)
Birmingham, Alabama, United States
RECRUITINGMayo Clinic
Scottsdale, Arizona, United States
RECRUITINGUrological Associates of South Arizona
Tucson, Arizona, United States
COMPLETEDArkansas Urology
Little Rock, Arkansas, United States
Phase 1: Nature, incidence, relatedness, and severity of all AEs and SAEs according to the CTCAE v5.0.
The type, incidence, relatedness and severity of treatment emergent adverse events of EG-70 as assessed by NCI-CTCAE V5.0 will be monitored.
Time frame: Approximately 2 years
Phase 2: Percentage of patients with cystoscopic CR at any time, based on exam, urine cytology and appropriate biopsies.
Complete response rate will be measured by determining the number of patients without recurrence of disease.
Time frame: Approximately 24 weeks
Phase 2: Nature, incidence, relatedness, and severity of treatment emergent adverse events (as assessed by CTCAE v5.0)
The type, incidence, relatedness and severity of treatment emergent adverse events of EG-70 as assessed by NCI-CTCAE V5.0 will be monitored.
Time frame: Approximately 3 years
Phase 1: The number of patients who experience a DLT through the end of Cycle 1
To identify the number of patients who experience a DLT through the end of Cycle 1
Time frame: Approximately 12 Weeks
Phase 1: CR rate to EG-70 by cystoscopy at approximately 12 weeks.
To evaluate preliminary efficacy of EG-70 by 12 weeks via cystoscopy
Time frame: Approximately 12 weeks
Phase 2: Duration of response of the responding patients
Durability will be measured by determining the number of patients without recurrence of high-grade disease.
Time frame: Approximately 3 years
Phase 2: Progression-free survival (PFS)
To evaluate disease-free survival rate
Time frame: Approximately 3 years
Phase 2: CR rate at 12, 24, 36, and 96 weeks
To further evaluate CR at the efficacy analysis following each cycle.
Time frame: Approximately 12, 24, 36, and 96 weeks
Phase 2: Quality of Life Assessment
Health-related quality of life
Time frame: 24 weeks
Chris Tosone
CONTACT
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University of California - Irvine Medical Center
Irvine, California, United States
RECRUITINGUC San Diego Moores Cancer Center
La Jolla, California, United States
RECRUITINGUSC/Norris Comprehensive Cancer Center
Los Angeles, California, United States
RECRUITINGTower Urology
Los Angeles, California, United States
RECRUITINGOm Research
San Diego, California, United States
RECRUITINGColorado Clinical Research
Lakewood, Colorado, United States
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