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

Phase 2
Terminated
Conditions
Urothelial Carcinoma
Interventions
Biological: DN24-02
Other: Standard of Care
Registration Number
NCT01353222
Lead Sponsor
Dendreon
Brief Summary

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.

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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
142
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
DN24-02DN24-02Subjects received infusion of DN24-02, at 2-week intervals, for a total of 3 infusions.
Standard of CareStandard of CareSubjects 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.
Primary Outcome Measures
NameTimeMethod
Overall SurvivalSubjects will be followed from baseline through the remainder of their lives or until study completion (approximately 60 months)

Overall survival is defined as the time from randomization to death due to any cause.

\*This study was terminated early due to administrative reasons.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (60)

Stanford University Hospital

🇺🇸

Stanford, California, United States

Columbia University Medical Center

🇺🇸

New York, New York, United States

USC/Norris Comprehensive Cancer Center

🇺🇸

Los Angeles, California, United States

Urology of Virginia, PLLC

🇺🇸

Virginia Beach, Virginia, United States

City of Hope Medical Center

🇺🇸

Duarte, California, United States

OHSU Knight Cancer Institute Hematology Oncology

🇺🇸

Beaverton, Oregon, United States

American Red Cross

🇺🇸

Atlanta, Georgia, United States

Urological Research Network

🇺🇸

Hialeah, Florida, United States

NYU Clinical Cancer Center, NYU Langone Medical Center

🇺🇸

New York, New York, United States

Mount Sinai School of Medicine

🇺🇸

New York, New York, United States

University of Chicago Medical Center

🇺🇸

Chicago, Illinois, United States

Urologic Specialists of Oklahoma

🇺🇸

Tulsa, Oklahoma, United States

Michigan Institute of Urology

🇺🇸

Troy, Michigan, United States

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

🇺🇸

Baltimore, Maryland, United States

The Ohio State University Wexner Medical Center, James Cancer Hospital, Martha Morehouse Medical Plaza, Ohio State University Dept of Urology

🇺🇸

Columbus, Ohio, United States

Roswell Park Cancer Institute

🇺🇸

Buffalo, New York, United States

Oregon Urology Institute

🇺🇸

Springfield, Oregon, United States

Associated Medical Professionals of New York, PLLC

🇺🇸

Syracuse, New York, United States

Associated Medical Professionals of NY, PLLC

🇺🇸

Oneida, New York, United States

Johns Hopkins Hospital

🇺🇸

Baltimore, Maryland, United States

Urology Health Specialists, LLC

🇺🇸

Bryn Mawr, Pennsylvania, United States

Sentara Leigh Hospital

🇺🇸

Norfolk, Virginia, United States

Dana Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

Virginia Mason Medical Center

🇺🇸

Seattle, Washington, United States

University of Miami Cancer Center

🇺🇸

Miami, Florida, United States

Indiana University

🇺🇸

Indianapolis, Indiana, United States

Emory Department of Urology, The Emory Clinic Inc, Emory University Hospital

🇺🇸

Atlanta, Georgia, United States

University of Kansas Cancer Center

🇺🇸

Westwood, Kansas, United States

GU Research Center, LLC

🇺🇸

Omaha, Nebraska, United States

Mount Sinai School of Medicine Department of Urology

🇺🇸

New York, New York, United States

Memorial Sloan Kettering

🇺🇸

New York, New York, United States

The University of Texas MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

UW Medical Center

🇺🇸

Seattle, Washington, United States

Genesis Research

🇺🇸

San Diego, California, United States

Jewish Hospital

🇺🇸

Cincinnati, Ohio, United States

TriState Urologic Services PSC, Inc. dba TUG Research

🇺🇸

Cincinnati, Ohio, United States

Hoxworth Blood Center

🇺🇸

Cincinnati, Ohio, United States

Kansas City Urology Care

🇺🇸

Overland Park, Kansas, United States

Mayo Clinic Arizona

🇺🇸

Scottsdale, Arizona, United States

University of Rochester Medical Center

🇺🇸

Rochester, New York, United States

University of Minnesota

🇺🇸

Minneapolis, Minnesota, United States

Duke University

🇺🇸

Durham, North Carolina, United States

Urology Associates, P.C.

🇺🇸

Nashville, Tennessee, United States

Vanderbilt University Medical Center

🇺🇸

Nashville, Tennessee, United States

Mayo Clinic Hospital

🇺🇸

Phoenix, Arizona, United States

University of Colorado, Anschutz Cancer Pavilion

🇺🇸

Aurora, Colorado, United States

The Urology Center of Colorado

🇺🇸

Denver, Colorado, United States

H. Lee Moffitt Cancer Center & Research Institute, Inc.

🇺🇸

Tampa, Florida, United States

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

Providence Medical Center

🇺🇸

Portland, Oregon, United States

Lahey Clinic

🇺🇸

Burlington, Massachusetts, United States

Fox Chase Cancer Center

🇺🇸

Philadelphia, Pennsylvania, United States

Neag Comprehensive Cancer Center/University of Connecticut Health Center

🇺🇸

Farmington, Connecticut, United States

John Theurer Cancer Center, Hackensack University Medical Center

🇺🇸

Hackensack, New Jersey, United States

Weill Cornell Medical College

🇺🇸

New York, New York, United States

Yale University School of Medicine

🇺🇸

New Haven, Connecticut, United States

UNC Health Care, NC Cancer Hospital

🇺🇸

Chapel Hill, North Carolina, United States

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

University of Wisconsin Carbone Cancer Center

🇺🇸

Madison, Wisconsin, United States

Thomas Jefferson University

🇺🇸

Philadelphia, Pennsylvania, United States

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