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Trial record 1 of 1 for:    NCT03219333
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A Study of Enfortumab Vedotin for Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer (EV-201)

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ClinicalTrials.gov Identifier: NCT03219333
Recruitment Status : Recruiting
First Posted : July 17, 2017
Last Update Posted : March 21, 2019
Sponsor:
Collaborator:
Seattle Genetics, Inc.
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Tracking Information
First Submitted Date  ICMJE July 13, 2017
First Posted Date  ICMJE July 17, 2017
Last Update Posted Date March 21, 2019
Actual Study Start Date  ICMJE October 8, 2017
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 22, 2018)
Objective response rate (ORR) by an independent review facility (IRF) [ Time Frame: Up to 3 years ]
The proportion of patients with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
Original Primary Outcome Measures  ICMJE
 (submitted: July 13, 2017)
Objective response rate (ORR) by an independent review facility (IRF) [ Time Frame: Up to 2 years ]
The proportion of patients with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
Change History Complete list of historical versions of study NCT03219333 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 3, 2019)
  • Duration of response (DOR) by an IRF [ Time Frame: Up to 7.5 years ]
    The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of progressive disease (PD) or to death due to any cause, whichever comes first
  • Disease control rate at 16 weeks (DCR16) by an IRF [ Time Frame: 16 weeks ]
    Proportion of patients with CR, PR, or stable disease (SD) at Week 16 visit
  • Progression free survival (PFS) by an IRF [ Time Frame: Up to 7.5 years ]
    The time from start of study treatment to first documentation of objective tumor progression (PD per RECIST 1.1), or to death due to any cause, whichever comes first
  • ORR by investigator assessment [ Time Frame: Up to 7.5 years ]
    Confirmed CR and PR per RECIST 1.1
  • DOR by investigator assessment [ Time Frame: Up to 7.5 years ]
    The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of PD or to death due to any cause, whichever comes first
  • DCR16 by investigator assessment [ Time Frame: 16 weeks ]
    Proportion of patients with CR, PR, or SD at Week 16 visit
  • Progression free survival (PFS) by investigator assessment [ Time Frame: Up to 7.5 years ]
    The time from start of study treatment to first documentation of objective tumor progression (PD per RECIST 1.1), or to death due to any cause, whichever comes first
  • Overall survival (OS) [ Time Frame: Up to 7.5 years ]
    The time from start of study treatment to date of death due to any cause
  • Incidence of adverse events (AEs) [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years ]
    Descriptive statistics will be used to summarize results
  • Incidence of laboratory abnormalities [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years ]
    Descriptive statistics will be used to summarize results
  • Pharmacokinetics (PK) parameter for enfortumab vedotin: Maximum concentration (Cmax) [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years ]
    Cmax will be derived from the PK blood samples collected
  • PK parameter for enfortumab vedotin: Trough concentration (Ctrough) [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years ]
    Ctrough will be derived from the PK blood samples collected
  • PK parameter for monomethyl auristatin E (MMAE): Cmax [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years ]
    Cmax will be derived from the PK blood samples collected
  • PK parameter for MMAE: Ctrough [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years ]
    Ctrough will be derived from the PK blood samples collected
  • PK parameter for Total Antibody (TAb): Cmax [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years ]
    Cmax will be derived from the PK blood samples collected
  • PK parameter for Total Antibody (TAb): Ctrough [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years ]
    Ctrough will be derived from the PK blood samples collected
  • Incidence of antitherapeutic antibodies (ATA) to enfortumab vedotin [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years ]
    Blood samples for ATA analysis will be collected
Original Secondary Outcome Measures  ICMJE
 (submitted: July 13, 2017)
  • Duration of response (DOR) by an IRF [ Time Frame: Up to 6.5 years ]
    The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of progressive disease (PD) or to death due to any cause, whichever comes first
  • Disease control rate at 16 weeks (DCR16) by an IRF [ Time Frame: 16 weeks ]
    Proportion of patients with CR, PR, or stable disease (SD) at Week 16 visit
  • Progression free survival (PFS) by an IRF [ Time Frame: Up to 6.5 years ]
    The time from start of study treatment to first documentation of objective tumor progression (PD per RECIST 1.1), or to death due to any cause, whichever comes first
  • ORR by investigator assessment [ Time Frame: Up to 6.5 years ]
    Confirmed CR and PR per RECIST 1.1
  • DOR by investigator assessment [ Time Frame: Up to 6.5 years ]
    The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of PD or to death due to any cause, whichever comes first
  • DCR16 by investigator assessment [ Time Frame: 16 weeks ]
    Proportion of patients with CR, PR, or SD at Week 16 visit
  • Progression free survival (PFS) by investigator assessment [ Time Frame: Up to 6.5 years ]
    The time from start of study treatment to first documentation of objective tumor progression (PD per RECIST 1.1), or to death due to any cause, whichever comes first
  • Overall survival (OS) [ Time Frame: Up to 6.5 years ]
    The time from start of study treatment to date of death due to any cause
  • Type, incidence, severity, seriousness, and relatedness of adverse events (AEs) [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 6.5 years ]
    Descriptive statistics will be used to summarize results
  • Laboratory abnormalities [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 6.5 years ]
    Descriptive statistics will be used to summarize results
  • Pharmacokinetics (PK) parameter for enfortumab vedotin: Maximum concentration (Cmax) [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 6.5 years ]
    Cmax will be derived from the PK blood samples collected
  • PK parameter for enfortumab vedotin: Trough concentration (Ctrough) [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 6.5 years ]
    Ctrough will be derived from the PK blood samples collected
  • PK parameter for monomethyl auristatin E (MMAE): Cmax [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 6.5 years ]
    Cmax will be derived from the PK blood samples collected
  • PK parameter for MMAE: Ctrough [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 6.5 years ]
    Ctrough will be derived from the PK blood samples collected
  • Incidence of antitherapeutic antibodies (ATA) to enfortumab vedotin [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 6.5 years ]
    Blood samples for ATA analysis will be collected
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Enfortumab Vedotin for Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer
Official Title  ICMJE A Single-arm, Open-label, Multicenter Study of Enfortumab Vedotin (ASG-22CE) for Treatment of Patients With Locally Advanced or Metastatic Urothelial Cancer Who Previously Received Immune Checkpoint Inhibitor (CPI) Therapy
Brief Summary

This is a study that will test how an experimental drug (enfortumab vedotin) affects patients with cancer of the urinary system (urothelial cancer). This type of cancer includes cancer of the bladder, renal pelvis, ureter or urethra that has spread to nearby tissues or to other areas of the body.

This clinical trial will enroll patients who were previously treated with a kind of anticancer drug called an immune checkpoint inhibitor (CPI). Some CPIs have been approved for the treatment of urothelial cancer.

This study will test if the cancer shrinks with treatment. This study will also look at the side effects of the drug. A side effect is a response to a drug that is not part of the treatment effect.

Patients who sign up for this trial must also fall into one of these categories:

  • Patients have already received treatment with platinum-containing chemotherapy
  • Patients have never received platinum-containing treatment and are not eligible for treatment with cisplatin.
Detailed Description This study will examine the safety and anticancer activity of enfortumab vedotin given intravenously to patients with locally advanced or metastatic urothelial cancer who previously received a CPI and either previously received platinum-containing chemotherapy (Cohort 1) or are platinum-naïve and cisplatin-ineligible (Cohort 2). Patients who received platinum in the adjuvant/neoadjuvant setting and did not progress within 12 months of completion will be considered platinum-naïve. Approximately 100 patients are expected to be enrolled in each cohort. The primary goal of the study is to determine the confirmed ORR of enfortumab vedotin.
Study Type  ICMJE Interventional
Study Phase Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Intervention Model Description:
single-arm, open-label, multi-cohort, multicenter study
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Carcinoma, Transitional Cell
  • Urinary Bladder Neoplasms
  • Urologic Neoplasms
  • Renal Pelvis Neoplasms
  • Urothelial Cancer
  • Ureteral Neoplasms
  • Urethral Neoplasms
Intervention  ICMJE Drug: Enfortumab vedotin
Intravenous (IV) infusion on days 1, 8 and 15 every 28 days
Other Names:
  • ASG-22CE
  • ASG-22ME
Study Arms Experimental: Enfortumab vedotin
Enfortumab vedotin on days 1, 8 and 15 every 28 days
Intervention: Drug: Enfortumab vedotin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 22, 2018)
200
Original Estimated Enrollment  ICMJE
 (submitted: July 13, 2017)
120
Estimated Study Completion Date May 2025
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically documented urothelial carcinoma (squamous differentiation or mixed cell types allowed).
  • Metastatic disease or locally advanced disease that is not resectable.
  • Must have received prior treatment with a CPI in the locally advanced or metastatic urothelial cancer setting. A CPI is defined as a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. Patients who received CPI therapy in the neoadjuvant/adjuvant setting and had recurrent or progressive disease either during therapy or within 3 months of therapy completion are eligible.
  • Must either have prior treatment with platinum-containing chemotherapy (Cohort 1) or be platinum-naïve and ineligible for treatment with cisplatin at time of enrollment (Cohort 2).
  • Must have had progression or recurrence of urothelial cancer during or following receipt of most recent therapy.
  • Tumor tissue samples must be available for submission to the sponsor prior to study treatment.
  • Must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1).
  • An Eastern Cooperative Oncology Group (ECOG) Performance Status score of ≤1 for Cohort 1 or ≤2 for Cohort 2.
  • Anticipated life expectancy of ≥3 months as assessed by the investigator.

Exclusion Criteria:

  • Ongoing sensory or motor neuropathy Grade ≥2.
  • Active central nervous system (CNS) metastases.
  • Immunotherapy related myocarditis, colitis, uveitis, or pneumonitis.
  • Prior enrollment in an enfortumab vedotin study or prior treatment with other monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs).
  • Uncontrolled tumor-related pain or impending spinal cord compression.
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE
Contact: Seattle Genetics Trial Information Support 866-333-7436 clinicaltrials@seagen.com
Listed Location Countries  ICMJE France,   Germany,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03219333
Other Study ID Numbers  ICMJE SGN22E-001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: Undecided
Responsible Party Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
Study Sponsor  ICMJE Astellas Pharma Global Development, Inc.
Collaborators  ICMJE Seattle Genetics, Inc.
Investigators  ICMJE
Study Director: Juan Pinelli, PA-C, MMSc Seattle Genetics, Inc.
PRS Account Astellas Pharma Inc
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP