Clinical trial NCT05014139: 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
Overall status: RECRUITING
Phase: PHASE1
Conditions: Urinary Bladder Neoplasms
Carcinoma in Situ
Carcinoma Transitional Cell
Non-muscle Invasive Bladder Cancer
NMIBC
Keywords: Bladder Cancer
Urothelial Cancer
Enfortumab vedotin
PADCEV
Pharmacokinetics
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: Seagen, a wholly owned subsidiary of Pfizer
First posted: 2021-08-20
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Incidence of adverse events (AEs)
timeFrame: Approximately 1 year
measure: Incidence of laboratory abnormalities
timeFrame: Approximately 1 year
measure: Incidence of dose limiting toxicities (DLTs)
timeFrame: Approximately 7 weeks
Secondary outcomes:
measure: Pharmacokinetics (PK) of enfortumab vedotin: Area under the concentration-time curve (AUC)
timeFrame: Approximately 1 year
measure: PK of enfortumab vedotin: Maximum concentration (Cmax)
timeFrame: Approximately 1 year
measure: PK of enfortumab vedotin: Time to maximum concentration concentration (tmax)
timeFrame: Approximately 1 year
measure: PK of enfortumab vedotin: Apparent terminal half-life (t1/2)
timeFrame: Approximately 1 year
measure: PK of enfortumab vedotin: Trough concentration (Ctrough)
timeFrame: Approximately 1 year
measure: Incidence of antitherapeutic antibodies (ATAs) to enfortumab vedotin
timeFrame: Approximately 1 year
measure: Complete response (CR) rate
timeFrame: Up to 24 months
measure: Duration of CR
timeFrame: Up to 5 years
measure: Rate of cystectomy
timeFrame: Up to 5 years
measure: Progression-free survival
timeFrame: Up to 5 years
measure: Cystectomy-free survival
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Los Angeles
country: United States
facility: UCLA Department of Medicine - Hematology & Oncology
state: California
city: Orange
country: United States
facility: University of California, Irvine
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: Stanford
country: United States
facility: Stanford Health Care
state: California
city: Chicago
country: United States
facility: Northwestern University-Feinberg School of Medicine
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Lexington
country: United States
facility: Markey Cancer Center / University of Kentucky
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Medical Center
state: Maryland
city: New York
country: United States
facility: Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: James Cancer Hospital / Ohio State University
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Sidney Kimmel Cancer Center
state: Pennsylvania
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Chattanooga
country: United States
facility: Erlanger Oncology and Hematology
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: San Antonio
country: United States
facility: Urology San Antonio
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center / Seattle Cancer Care Alliance / University of Washington
state: Washington
city: Toronto
country: Canada
facility: Site CA11001
state: Ontario
city: Lyon
country: France
facility: Site FR33002
city: Paris
country: France
facility: Site FR33001
city: Rennes
country: France
facility: Site FR33003
city: Goettingen
country: Germany
facility: Site DE49001
city: Tübingen
country: Germany
facility: Site DE49002
city: Barcelona
country: Spain
facility: Site ES34001
city: Barcelona
country: Spain
facility: Site ES34004
city: Barcelona
country: Spain
facility: Site ES34003
city: Madrid
country: Spain
facility: Site ES34002
city: London
country: United Kingdom
facility: Site UK44002
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: