A Study of Intravesical Enfortumab Vedotin For Treatment of Patients With Non-muscle Invasive Bladder Cancer (NMIBC)
- Conditions
- Urinary Bladder NeoplasmsNMIBCCarcinoma Transitional CellNon-muscle Invasive Bladder CancerCarcinoma in Situ
- Interventions
- Drug: Enfortumab vedotin
- Registration Number
- NCT05014139
- Lead Sponsor
- Astellas Pharma Global Development, Inc.
- Brief Summary
This study will test a drug called enfortumab vedotin in participants with a type of bladder cancer called non-muscle invasive bladder cancer (NMIBC).
This study will also evaluate what the side effects are and if the drug works to treat NMIBC. A side effect is anything a drug does to your body besides treating your disease.
In this study enfortumab vedotin will be put into the bladder using a catheter. A catheter is a thin tube that can be put into your bladder.
- Detailed Description
The study will be comprised of 2 parts. The first part (dose escalation) will find the highest dose of enfortumab vedotin that does not cause unacceptable side effects in participants. The second part (dose expansion) will use the dose found in the first part to test how well the drug works.
All participants will receive enfortumab vedotin. Treatment on the study will occur during the induction and maintenance phases, and participants will enter a follow-up period after completion of the maintenance phase.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 58
-
Histologically confirmed, non-muscle invasive urothelial carcinoma with carcinoma in situ (CIS) (with or without papillary disease)
-
Predominant histologic component (>50 percent) must be urothelial (transitional cell) carcinoma
-
Participants must have high-risk Bacillus Calmette-Guerin (BCG) - unresponsive disease, defined as (where adequate BCG therapy is defined as one of the following: 5 of 6 doses of an initial induction course + at least 2 of 3 doses maintenance therapy or 5 of 6 doses of an initial induction course + at least 2 of 6 doses of a second induction course):
- Persistent or recurrent CIS alone or with recurrent Ta/T1 (noninvasive papillary disease/tumor invades the subepithelial connective tissue) disease within 12 months of completion of adequate BCG therapy.
- Recurrent high-grade Ta/T1 disease within 6 months of completion of adequate BCG therapy, or
- T1 high-grade disease at the first evaluation following an induction BCG course (at least 5 or 6 doses)
-
Participant must be ineligible for or refusing a radical cystectomy
-
All visible papillary Ta/T1 tumors must be completely resected within 60 days prior to enrollment.
-
Eastern Cooperative Oncology Group Performance Status score of 0, 1, or 2.
- Current or prior history of muscle-invasive urothelial carcinoma or metastatic disease.
- Nodal or metastatic disease as noted on computed tomography (CT) or magnetic resonance imaging (MRI) within 3 months prior to study treatment
- Concomitant upper tract urothelial carcinoma as noted on CT or MRI urogram performed within 3 months prior to study treatment
- Prior or concomitant urothelial carcinoma of the prostatic urethra within 6 months prior to study treatment
- Participants with tumor-related hydronephrosis
- Participant has received other systemic anticancer therapy including chemotherapy, biologic therapy, immunotherapy, targeted therapy, endocrine therapy, and/or investigational agent within 4 weeks or intravesical therapy within 6 weeks of first dose of study treatment
- Participant has had any prior radiation to the bladder for urothelial cancer
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Enfortumab vedotin: Dose escalation cohort Enfortumab vedotin During the induction phase, participants will receive enfortumab vedotin once a week for 6 weeks. During the maintenance phase, participants will receive enfortumab vedotin once a month for 9 doses. Enfortumab vedotin: Dose expansion cohort Enfortumab vedotin During the induction phase, participants will receive enfortumab vedotin once a week for 6 weeks. During the maintenance phase, participants will receive enfortumab vedotin once a month for 9 doses.
- Primary Outcome Measures
Name Time Method Incidence of adverse events (AEs) Approximately 1 year An AE is any untoward medical occurrence in a subject or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
Incidence of laboratory abnormalities Approximately 1 year To be summarized using descriptive statistics.
Incidence of dose limiting toxicities (DLTs) Approximately 7 weeks To be summarized using descriptive statistics.
- Secondary Outcome Measures
Name Time Method Rate of cystectomy Up to 5 years The proportion of subjects who subsequently undergo cystectomy.
Pharmacokinetics (PK) of enfortumab vedotin: Area under the concentration-time curve (AUC) Approximately 1 year AUC will be recorded from the PK blood samples collected.
PK of enfortumab vedotin: Time to maximum concentration concentration (tmax) Approximately 1 year Tmax will be recorded from the PK blood samples collected.
PK of enfortumab vedotin: Apparent terminal half-life (t1/2) Approximately 1 year T1/2 will be recorded from the PK blood samples collected.
Incidence of antitherapeutic antibodies (ATAs) to enfortumab vedotin Approximately 1 year Blood samples for ATA analysis will be collected.
Complete response (CR) rate Up to 24 months CR rate is defined as the proportion of subjects achieving CR.
Progression-free survival Up to 5 years The time from start of study treatment to the first evidence of progression or death due to any cause.
Cystectomy-free survival Up to 5 years The time from start of study treatment to cystectomy or death due to any cause.
PK of enfortumab vedotin: Maximum concentration (Cmax) Approximately 1 year Cmax will be recorded from the PK blood samples collected.
PK of enfortumab vedotin: Trough concentration (Ctrough) Approximately 1 year Ctrough will be recorded from the PK blood samples collected.
Duration of CR Up to 5 years The time from first documented CR to the first evidence of recurrence, progression, or death due to any cause.
Trial Locations
- Locations (32)
Mayo Clinic
🇺🇸Scottsdale, Arizona, United States
UCLA Department of Medicine - Hematology & Oncology
🇺🇸Los Angeles, California, United States
James Cancer Hospital / Ohio State University
🇺🇸Columbus, Ohio, United States
Stanford Health Care
🇺🇸Stanford, California, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
University of California, Irvine
🇺🇸Orange, California, United States
University of California at San Francisco
🇺🇸San Francisco, California, United States
Northwestern University-Feinberg School of Medicine
🇺🇸Chicago, Illinois, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Markey Cancer Center / University of Kentucky
🇺🇸Lexington, Kentucky, United States
Johns Hopkins Medical Center
🇺🇸Baltimore, Maryland, United States
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
🇺🇸New York, New York, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Sidney Kimmel Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Carolina Urologic Research Center
🇺🇸Myrtle Beach, South Carolina, United States
Erlanger Oncology and Hematology
🇺🇸Chattanooga, Tennessee, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
MD Anderson
🇺🇸Houston, Texas, United States
Urology San Antonio
🇺🇸San Antonio, Texas, United States
Fred Hutchinson Cancer Center / Seattle Cancer Care Alliance / University of Washington
🇺🇸Seattle, Washington, United States
Site CA11001
🇨🇦Toronto, Ontario, Canada
Site FR33002
🇫🇷Lyon, France
Site FR33001
🇫🇷Paris, France
Site FR33003
🇫🇷Rennes, France
Site DE49001
🇩🇪Goettingen, Germany
Site DE49002
🇩🇪Tübingen, Germany
Site ES34001
🇪🇸Barcelona, Spain
Site ES34004
🇪🇸Barcelona, Spain
Site ES34003
🇪🇸Barcelona, Spain
Site ES34002
🇪🇸Madrid, Spain
Site UK44002
🇬🇧London, United Kingdom