Study of Cretostimogene Given in Patients With Non-Muscle Invasive Bladder Cancer ,Unresponsive to Bacillus-Calmette-Guerin
- Conditions
- High-grade Ta/ T1 Papillary Disease Bladder CancerNon Muscle Invasive Bladder Cancer
- Interventions
- Other: n-dodecyl-B-D-maltoside
- Registration Number
- NCT04452591
- Lead Sponsor
- CG Oncology, Inc.
- Brief Summary
This is a Phase 3, open-label, single arm trial designed to evaluate Cretostimogene patients with NMIBC who have failed prior BCG therapy. Up to approximately 115 CIS bladder cancer patients with or without HG Ta or HG T1 papillary disease will be enrolled under the original protocol through Amendment 4, which will comprise Cohort C. Cohort C is closed to enrollment.
Under Amendment 5-1, Cohort P was added to enroll up to 70 patients with HG Ta/T1 papillary bladder cancer.
Under Amendment 6, the target number of patients enrolled in Cohort P was increased to 75. Cohort P is open to enrollment
Cohort C and Cohort P will be analyzed and reported separately. Patients will have had to fail prior BCG therapy which is defined as having persistent or recurrent disease within 12 months (Cohort C) or 6 months (Cohort P) following the completion of adequate BCG therapy for HGUC
- Detailed Description
Cohort C(All Countries) :
An open-label trial designed to evaluate Cretostimogene + DDM in patients with NMIBC who have failed prior BCG therapy. Single treatment arm that enrolled 115 patients with carcinoma in situ with or without concomitant high-grade Ta or T1 papillary disease
BCG failure is defined as a persistent or recurrent disease within 12 months of completion of adequate BCG therapy.
Cohort P(Japan and the United States Only):
To determine the all-cause High Grade Event Free Survival (HG-EFS) of cretostimogene in up to 75 patients with BCG-unresponsive HG Ta/T1 papillary disease without CIS.
BCG failure is defined as a persistent or recurrent disease within 6 months of completion of adequate BCG therapy.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 190
Not provided
- Has current or past history of muscle invasive (T2 or higher stage) or locally advanced (T3/T4, any N) or metastatic bladder cancer.
- Any HGUC as T1, HG Ta, or CIS in the upper genitourinary tract or prostatic urethra (including CIS of the urethra) within 24 months prior to enrollment OR any history of T2 or higher stage urothelial carcinoma in the upper genitourinary tract (kidneys, renal collecting systems, ureters).
- Has received systemic anti-cancer therapy, including investigational agents, within 4 weeks of Day 1.
- Has had prior systemic treatment (with the exception of checkpoint inhibitor therapy), radiation therapy, or surgery for bladder cancer other than TURBT or bladder biopsies.
- Has any of the following within the 6 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident, pulmonary embolus, uncontrolled hypertension, or uncontrolled congestive heart failure.
- Cannot tolerate study-related biopsies, IVE administration, or 1-hour bladder hold of cretostimogene.
- IVE therapy within 8 weeks prior to beginning study treatment with the exception of cytotoxic agents (e.g., Mitomycin C, gemcitabine, doxorubicin and epirubicin) when administered as a single instillation immediately following a TURBT procedure which is permitted 14 or more days prior to beginning study treatment
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Cohort P(Japan and United States Only) :Open to Enrollment Cretostimogene Grenadenorepvec HG Ta/T1 papillary disease bladder cancer patients. In Cohort P, cretostimogene will be administered at a dose of 1 × 1012vp IVE following instillation of 5% DDM. Cretostimogene will be administered every week for 6 treatments on Weeks 1, 2, 3, 4, 5, and 6. If the patient has recurrence at Week 13 or any timepoint, the patient will receive a second induction of 6 weekly treatments (Weeks 13, 14, 15, 16, 17, and 18.). If the tumor has not returned they will receive 3 weekly treatments every 12 weeks (approximately 3 months) starting Weeks 13, 14, and 15 through Week 51 (approximately 12 months), and then every 6 months starting at Weeks 73, 74, and 75 (approximately 18 months) through Month 36. Cohort P(Japan and United States Only) :Open to Enrollment n-dodecyl-B-D-maltoside HG Ta/T1 papillary disease bladder cancer patients. In Cohort P, cretostimogene will be administered at a dose of 1 × 1012vp IVE following instillation of 5% DDM. Cretostimogene will be administered every week for 6 treatments on Weeks 1, 2, 3, 4, 5, and 6. If the patient has recurrence at Week 13 or any timepoint, the patient will receive a second induction of 6 weekly treatments (Weeks 13, 14, 15, 16, 17, and 18.). If the tumor has not returned they will receive 3 weekly treatments every 12 weeks (approximately 3 months) starting Weeks 13, 14, and 15 through Week 51 (approximately 12 months), and then every 6 months starting at Weeks 73, 74, and 75 (approximately 18 months) through Month 36. Cohort C(All Countries):Enrollment Closed Cretostimogene Grenadenorepvec Patients with CIS with or without HG Ta/T1 papillary disease. Cretostimogene will be administered intravesically following a series of bladder washes with 5% DDM and normal saline. Cretostimogene will be administered weekly x 6 on Weeks 1, 2, 3, 4, 5, and 6. If the patient has disease recurrence at Week 13, they will receive another cycle of 6 weekly treatments. If there is no disease present at Week 13 then the patient will receive 3 weekly treatments. Cohort C(All Countries):Beginning at Week 25, patients will receive weekly x 3 treatments every 12 weeks through week 51 then every 6 months and then a last treatment at Weeks 73, 74, and 75 until the tumor returns or study treatment is completed at Week 97. Cohort C Extension( Japan and the US) At Week 25, patients will receive weekly x 3 treatments every 12 weeks through week 51 then every 6 months starting at Weeks 73, 74, and 75 through Weeks 157, 158, and 159 until the tumor returns or study treatment is completed at Week 159. Cohort C(All Countries):Enrollment Closed n-dodecyl-B-D-maltoside Patients with CIS with or without HG Ta/T1 papillary disease. Cretostimogene will be administered intravesically following a series of bladder washes with 5% DDM and normal saline. Cretostimogene will be administered weekly x 6 on Weeks 1, 2, 3, 4, 5, and 6. If the patient has disease recurrence at Week 13, they will receive another cycle of 6 weekly treatments. If there is no disease present at Week 13 then the patient will receive 3 weekly treatments. Cohort C(All Countries):Beginning at Week 25, patients will receive weekly x 3 treatments every 12 weeks through week 51 then every 6 months and then a last treatment at Weeks 73, 74, and 75 until the tumor returns or study treatment is completed at Week 97. Cohort C Extension( Japan and the US) At Week 25, patients will receive weekly x 3 treatments every 12 weeks through week 51 then every 6 months starting at Weeks 73, 74, and 75 through Weeks 157, 158, and 159 until the tumor returns or study treatment is completed at Week 159.
- Primary Outcome Measures
Name Time Method Cohort P: 36 months To determine the high-grade EFS of cretostimogene in patients with BCG-unresponsive HG Ta/T1 papillary disease without CIS.Ta/T1 papillary disease without CIS.
Cohort C: 36 months To determine the Complete Response rate at any time in patients with BCG-unresponsive CIS with or without concomitant HG Ta/T1 papillary disease.
- Secondary Outcome Measures
Name Time Method Cohort C: Duration of response (DOR) 36 months Median duration of response in patients with a CR or PR in subjects
Cohort C:Complete Response rate at 12 months 12 months Cohort C: Reoccurrence free survival up to 60 months Cohort C and Cohort P: Assess progression free survival (PFS ) up to 60 months Cohort C and Cohort P : Cystectomy free survival up to 60 months Cohort C: Assess overall survival up to 60 months Cohort C and Cohort P: Assess high-grade reoccurrence free survival (RFS) up to 60 months Cohort C and Cohort P: Evaluate the safety of Cretostimogene 36 months
Trial Locations
- Locations (70)
Mayo Clinic Cancer Center
🇺🇸Phoenix, Arizona, United States
Arizona Institute of Urology
🇺🇸Tucson, Arizona, United States
Arkansas Urology
🇺🇸Little Rock, Arkansas, United States
University of California - Irvine
🇺🇸Irvine, California, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
Colorado Clinical Research
🇺🇸Lakewood, Colorado, United States
Urology Associates
🇺🇸Lone Tree, Colorado, United States
MedStar Hospital
🇺🇸Washington, District of Columbia, United States
Mayo Clinic - Jacksonville
🇺🇸Jacksonville, Florida, United States
Moffit Cancer Center
🇺🇸Tampa, Florida, United States
Scroll for more (60 remaining)Mayo Clinic Cancer Center🇺🇸Phoenix, Arizona, United StatesClinical Trials Office All Mayo Clinic LocationsContact855-776-0015Mark Tyson, MDPrincipal Investigator