DN24-02 as Adjuvant Therapy in Subjects With High Risk HER2+ Urothelial Carcinoma

A Randomized, Phase 2, Open-label Study Evaluating DN24-02 as Adjuvant Therapy in Subjects With High Risk HER2+ Urothelial Carcinoma

This study was conducted to examine survival, disease-free survival, safety, and the magnitude of the immune response induced following administration of DN24-02 in subjects with HER2+ urothelial carcinoma.

Study Overview

• Status: Terminated
• Conditions: Urothelial Carcinoma
• Intervention / Treatment: Biological: DN24-02; Other: Standard of Care

Detailed Description

Multicenter, open-label, Phase 2 study. Subjects were randomized to either the investigational product, DN24-02, or to standard of care. Subjects randomized to the experimental arm received DN24-02 at 2-week intervals, for a total of 3 infusions. The study evaluated survival, disease-free survival, safety and the magnitude of the immune response between these 2 subject groups.

• Study Type: Interventional
• Enrollment (Actual): 142
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Hospital
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Arizona
  • California
    • Duarte, California, United States, 91010
      • City of Hope Medical Center
    • Los Angeles, California, United States, 90033
      • USC/Norris Comprehensive Cancer Center
    • San Diego, California, United States, 92123
      • Genesis Research
    • Stanford, California, United States, 94305
      • Stanford University Hospital
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado, Anschutz Cancer Pavilion
    • Denver, Colorado, United States, 80211
      • The Urology Center of Colorado
  • Connecticut
    • Farmington, Connecticut, United States, 06030
      • Neag Comprehensive Cancer Center/University of Connecticut Health Center
    • New Haven, Connecticut, United States, 06520
      • Yale University School of Medicine
  • Florida
    • Hialeah, Florida, United States, 33016
      • Urological Research Network
    • Miami, Florida, United States, 33136
      • University of Miami Cancer Center
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center & Research Institute, Inc.
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Department of Urology, The Emory Clinic Inc, Emory University Hospital
    • Atlanta, Georgia, United States, 30324
      • American Red Cross
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • Kansas City Urology Care
    • Westwood, Kansas, United States, 66205
      • University of Kansas Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
    • Baltimore, Maryland, United States, 21231
      • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
    • Burlington, Massachusetts, United States, 01805
      • Lahey Clinic
  • Michigan
    • Troy, Michigan, United States, 48084
      • Michigan Institute of Urology
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • GU Research Center, LLC
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center, Hackensack University Medical Center
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
    • New York, New York, United States, 10021
      • Memorial Sloan Kettering
    • New York, New York, United States, 10016
      • NYU Clinical Cancer Center, NYU Langone Medical Center
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine Department of Urology
    • Oneida, New York, United States, 13421
      • Associated Medical Professionals of NY, PLLC
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
    • Syracuse, New York, United States, 13210
      • Associated Medical Professionals of New York, PLLC
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • UNC Health Care, NC Cancer Hospital
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • Jewish Hospital
    • Cincinnati, Ohio, United States, 45219
      • Hoxworth Blood Center
    • Cincinnati, Ohio, United States, 45212
      • TriState Urologic Services PSC, Inc. dba TUG Research
    • Columbus, Ohio, United States, 43210, 43221, 43212
      • The Ohio State University Wexner Medical Center, James Cancer Hospital, Martha Morehouse Medical Plaza, Ohio State University Dept of Urology
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74146
      • Urologic Specialists of Oklahoma
  • Oregon
    • Beaverton, Oregon, United States, 97006
      • OHSU Knight Cancer Institute Hematology Oncology
    • Portland, Oregon, United States, 97213
      • Providence Medical Center
    • Springfield, Oregon, United States, 97477
      • Oregon Urology Institute
  • Pennsylvania
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Urology Health Specialists, LLC
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
    • Nashville, Tennessee, United States, 37209
      • Urology Associates, P.C.
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Sentara Leigh Hospital
    • Virginia Beach, Virginia, United States, 23462
      • Urology of Virginia, PLLC
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
    • Seattle, Washington, United States, 98195
      • UW Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Carbone Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histopathologic evidence of urothelial carcinoma, based on local pathology report.
• High risk urothelial carcinoma, in subjects with or without prior neoadjuvant chemotherapy, defined as positive lymph node status (N+), or pathological stage ≥ pathological tumor (pT2) in patients who either have negative lymph node status (N0) or have no evaluable lymph nodes (Nx).
• Radical surgical resection was performed ≤ 84 days (12 weeks) prior to registration.
• No evidence of residual disease or metastasis following surgical resection which includes: absence of invasive cancer at the margins in the surgical specimens and confirmation by CT scan of chest, abdomen and pelvis obtained at least 28 days following surgical resection and ≤ 28 days prior to registration.
• HER2/neu tissue expression ≥ 1+ by immunohistochemistry (IHC). Available biopsy specimens from the primary tumor and involved lymph nodes are be submitted to the central pathology laboratory prior to registration for confirmation of HER2/neu tissue expression.
• Last neoadjuvant chemotherapy treatment administered at least 60 days prior to registration.
• Left ventricular ejection fraction ≥ 50% on multigated acquisition (MUGA) scan or echocardiogram obtained at least 28 days following surgery and ≤ 28 days prior to registration.
• Women of child-bearing potential have a negative serum pregnancy test result ≤ 28 days prior to registration and agree not to breastfeed during investigational treatment with DN24-02 and for 28 days following the final infusion of DN24-02.
• All males and premenopausal females who have not been surgically sterilized have agreed to practice a method of birth control considered by the Investigator to be effective and medically acceptable for at least 14 days prior to registration, throughout treatment, and for 28 days following the final infusion of DN24-02.
• Adequate hematologic, renal, and liver function.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

Exclusion Criteria:

• A history of stage III or greater non-urothelial cancer. Exceptions include: Subject with basal or squamous cell skin cancers that has been adequately treated who are disease-free at the time of registration. Subjects who have been disease-free and off treatment for ≥ 10 years at the time of registration.
• A history of stage I or II non-urothelial cancer. Exceptions include: Subjects who have been disease-free and off treatment for ≥ 3 years at the time of registration. Subjects with incidental prostate cancer diagnosed at the time of cystoprostatectomy. Subjects with basal or squamous cell skin cancer.
• Partial cystectomy in the setting of bladder cancer primary tumor.
• Partial nephrectomy in the setting of renal pelvis primary tumor.
• Adjuvant systemic therapy for urothelial or prostatic carcinoma following surgical resection.
• Adjuvant radiation therapy for urothelial or prostatic carcinoma following surgical resection.
• Incidental prostate cancer with detectable post-operative (radical cystoprostatectomy) prostate specific antigen (PSA) levels ≤ 28 days prior to registration.
• Any major surgery (e.g., surgery requiring general anesthesia) ≤ 28 days prior to registration.
• Systemic treatment on any investigational clinical trial ≤ 28 days prior to registration.
• Systemic glucocorticoid or immunosuppressive therapy use ≤ 28 days prior to registration.
• Any infection requiring parenteral antibiotic therapy or causing fever (i.e., temperature > 100.5°F or > 38.1°C) ≤ 7 days prior to registration.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to DN24-02 or Granulocyte-macrophage colony-stimulating factor (GM-CSF).
• Any medical intervention, has any other condition, or has any other circumstance which, in the opinion of the Investigator or the Dendreon Medical Monitor, could compromise adherence with study requirements or otherwise compromise the study's objectives.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: DN24-02; Subjects received infusion of DN24-02, at 2-week intervals, for a total of 3 infusions.	Biological: DN24-02; DN24-02 is an autologous cellular immunotherapy product designed to stimulate an immune response against HER2/neu. It consists of autologous peripheral blood mononuclear cells (PBMCs), including antigen presenting cells (APCs), which are activated ex vivo with a recombinant fusion protein, BA7072.
OTHER: Standard of Care; Subjects randomized to the control arm were treated per standard of care, which in this patient population is generally observation, as there is currently no evidence that treatment with non-cisplatin containing chemotherapy is beneficial in the adjuvant setting for this patient population.	Other: Standard of Care; Observation only until documentation of disease recurrence.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival is defined as the time from randomization to death due to any cause. *This study was terminated early due to administrative reasons.	Subjects will be followed from baseline through the remainder of their lives or until study completion (approximately 60 months)

Collaborators and Investigators

• Sponsor: Dendreon

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (ACTUAL): July 1, 2015
• Study Completion (ACTUAL): July 1, 2015

Study Registration Dates

• First Submitted: May 4, 2011
• First Submitted That Met QC Criteria: May 11, 2011
• First Posted (ESTIMATE): May 13, 2011

Study Record Updates

• Last Update Posted (ACTUAL): May 25, 2017
• Last Update Submitted That Met QC Criteria: April 21, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Neoplasms; Bladder cancer; Vaccine; Immunotherapy; Ureter; Bladder; Cancer vaccine; Urothelial carcinoma; Immune therapy; Dendritic cells; Urethra; Neoplasms by site; Renal pelvis; Renal pelvis cancer; Ureteral cancer; Urethral cancer; Antigen-presenting cells; Antigen presenting cells; Urothelial neoplasms
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Transitional Cell
• Other Study ID Numbers: N10-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED