Back to resultsA Study of Intravesical Enfortumab Vedotin For Treatment of Patients With Non-muscle Invasive Bladder Cancer (NMIBC)
Primary Purpose
Urinary Bladder Neoplasms, Carcinoma in Situ, Carcinoma Transitional Cell
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Enfortumab vedotin
Sponsored by
About this trial
This is an interventional treatment trial for Urinary Bladder Neoplasms focused on measuring Bladder Cancer, Urothelial Cancer, Enfortumab vedotin, PADCEV, Pharmacokinetics
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
Sites / Locations
- UCLA Department of Medicine - Hematology & OncologyRecruiting
- University of California, IrvineRecruiting
- University of California at San FranciscoRecruiting
- Johns Hopkins Medical CenterRecruiting
- Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
- Duke University Medical Center
- University of Texas Southwestern Medical CenterRecruiting
- MD AndersonRecruiting
- Site CA11001Recruiting
- Site FR33001Recruiting
- Site ES34001Recruiting
- Site ES34003Recruiting
- Site ES34002Recruiting
- Site UK44002Recruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Enfortumab vedotin: Dose escalation cohort
Enfortumab vedotin: Dose expansion cohort
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Incidence of adverse events (AEs)
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
To be summarized using descriptive statistics.
Incidence of dose limiting toxicities (DLTs)
To be summarized using descriptive statistics.
Secondary Outcome Measures
Pharmacokinetics (PK) of enfortumab vedotin: Area under the concentration-time curve (AUC)
AUC will be recorded from the PK blood samples collected.
PK of enfortumab vedotin: Maximum concentration (Cmax)
Cmax will be recorded from the PK blood samples collected.
PK of enfortumab vedotin: Time to maximum concentration concentration (tmax)
Tmax will be recorded from the PK blood samples collected.
PK of enfortumab vedotin: Apparent terminal half-life (t1/2)
T1/2 will be recorded from the PK blood samples collected.
PK of enfortumab vedotin: Trough concentration (Ctrough)
Ctrough will be recorded from the PK blood samples collected.
Incidence of antitherapeutic antibodies (ATAs) to enfortumab vedotin
Blood samples for ATA analysis will be collected.
Complete response (CR) rate
CR rate is defined as the proportion of subjects achieving CR.
Duration of CR
The time from first documented CR to the first evidence of recurrence, progression, or death due to any cause.
Rate of cystectomy
The proportion of subjects who subsequently undergo cystectomy.
Progression-free survival
The time from start of study treatment to the first evidence of progression or death due to any cause.
Cystectomy-free survival
The time from start of study treatment to cystectomy or death due to any cause.
Full Information
NCT ID
NCT05014139
First Posted
August 16, 2021
Last Updated
August 21, 2023
Sponsor
Astellas Pharma Global Development, Inc.
Collaborators
Seagen Inc.
1. Study Identification
Unique Protocol Identification Number
NCT05014139
Brief Title
A Study of Intravesical Enfortumab Vedotin For Treatment of Patients With Non-muscle Invasive Bladder Cancer (NMIBC)
Official Title
A Study of Intravesical Enfortumab Vedotin For Treatment of Patients With Non-muscle Invasive Bladder Cancer (NMIBC)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 7, 2021 (Actual)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
May 31, 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Astellas Pharma Global Development, Inc.
Collaborators
Seagen Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Urinary Bladder Neoplasms, Carcinoma in Situ, Carcinoma Transitional Cell, Non-muscle Invasive Bladder Cancer, NMIBC
Keywords
Bladder Cancer, Urothelial Cancer, Enfortumab vedotin, PADCEV, Pharmacokinetics
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
58 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Enfortumab vedotin: Dose escalation cohort
Arm Type
Experimental
Arm Description
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.
Arm Title
Enfortumab vedotin: Dose expansion cohort
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Enfortumab vedotin
Other Intervention Name(s)
PADCEV, ASG-22CE, ASG-22ME
Intervention Description
Given into the bladder (intravesically)
Primary Outcome Measure Information:
Title
Incidence of adverse events (AEs)
Description
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.
Time Frame
Approximately 1 year
Title
Incidence of laboratory abnormalities
Description
To be summarized using descriptive statistics.
Time Frame
Approximately 1 year
Title
Incidence of dose limiting toxicities (DLTs)
Description
To be summarized using descriptive statistics.
Time Frame
Approximately 7 weeks
Secondary Outcome Measure Information:
Title
Pharmacokinetics (PK) of enfortumab vedotin: Area under the concentration-time curve (AUC)
Description
AUC will be recorded from the PK blood samples collected.
Time Frame
Approximately 1 year
Title
PK of enfortumab vedotin: Maximum concentration (Cmax)
Description
Cmax will be recorded from the PK blood samples collected.
Time Frame
Approximately 1 year
Title
PK of enfortumab vedotin: Time to maximum concentration concentration (tmax)
Description
Tmax will be recorded from the PK blood samples collected.
Time Frame
Approximately 1 year
Title
PK of enfortumab vedotin: Apparent terminal half-life (t1/2)
Description
T1/2 will be recorded from the PK blood samples collected.
Time Frame
Approximately 1 year
Title
PK of enfortumab vedotin: Trough concentration (Ctrough)
Description
Ctrough will be recorded from the PK blood samples collected.
Time Frame
Approximately 1 year
Title
Incidence of antitherapeutic antibodies (ATAs) to enfortumab vedotin
Description
Blood samples for ATA analysis will be collected.
Time Frame
Approximately 1 year
Title
Complete response (CR) rate
Description
CR rate is defined as the proportion of subjects achieving CR.
Time Frame
Up to 24 months
Title
Duration of CR
Description
The time from first documented CR to the first evidence of recurrence, progression, or death due to any cause.
Time Frame
Up to 5 years
Title
Rate of cystectomy
Description
The proportion of subjects who subsequently undergo cystectomy.
Time Frame
Up to 5 years
Title
Progression-free survival
Description
The time from start of study treatment to the first evidence of progression or death due to any cause.
Time Frame
Up to 5 years
Title
Cystectomy-free survival
Description
The time from start of study treatment to cystectomy or death due to any cause.
Time Frame
Up to 5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Seagen, Inc. Trial Information Support
Phone
866-333-7436
Email
clinicaltrials@seagen.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janet Trowbridge, MD
Organizational Affiliation
Seagen Inc.
Official's Role
Study Director
Facility Information:
Facility Name
UCLA Department of Medicine - Hematology & Oncology
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Individual Site Status
Recruiting
Facility Name
University of California, Irvine
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Individual Site Status
Recruiting
Facility Name
University of California at San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94134
Country
United States
Individual Site Status
Recruiting
Facility Name
Johns Hopkins Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Individual Site Status
Recruiting
Facility Name
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Completed
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Individual Site Status
Completed
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Individual Site Status
Recruiting
Facility Name
MD Anderson
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Name
Site CA11001
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C1
Country
Canada
Individual Site Status
Recruiting
Facility Name
Site FR33001
City
Paris
ZIP/Postal Code
75013
Country
France
Individual Site Status
Recruiting
Facility Name
Site ES34001
City
Barcelona
ZIP/Postal Code
08025
Country
Spain
Individual Site Status
Recruiting
Facility Name
Site ES34003
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Individual Site Status
Recruiting
Facility Name
Site ES34002
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Individual Site Status
Recruiting
Facility Name
Site UK44002
City
London
ZIP/Postal Code
EC1A 7BE
Country
United Kingdom
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study of Intravesical Enfortumab Vedotin For Treatment of Patients With Non-muscle Invasive Bladder Cancer (NMIBC)
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