Clinical trial NCT01353222: DN24-02 as Adjuvant Therapy in Subjects With High Risk HER2+ Urothelial Carcinoma
Official title: A Randomized, Phase 2, Open-label Study Evaluating DN24-02 as Adjuvant Therapy in Subjects With High Risk HER2+ Urothelial Carcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Urothelial Carcinoma
Keywords: Bladder cancer
Renal pelvis cancer
Ureteral cancer
Urethral cancer
Bladder
Renal pelvis
Ureter
Urethra
Immune therapy
Immunotherapy
Vaccine
Dendritic cells
Antigen-presenting cells
Antigen presenting cells
Cancer vaccine
Urothelial carcinoma
Urothelial neoplasms
Neoplasms by site
Neoplasms
Lead sponsor: Dendreon
Sponsor class: INDUSTRY
First posted: 2011-05-13
Enrollment: 142
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall Survival
timeFrame: Subjects will be followed from baseline through the remainder of their lives or until study completion (approximately 60 months)
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: San Diego
country: United States
facility: Genesis Research
state: California
city: Stanford
country: United States
facility: Stanford University Hospital
state: California
city: Aurora
country: United States
facility: University of Colorado, Anschutz Cancer Pavilion
state: Colorado
city: Denver
country: United States
facility: The Urology Center of Colorado
state: Colorado
city: Farmington
country: United States
facility: Neag Comprehensive Cancer Center/University of Connecticut Health Center
state: Connecticut
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Hialeah
country: United States
facility: Urological Research Network
state: Florida
city: Miami
country: United States
facility: University of Miami Cancer Center
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute, Inc.
state: Florida
city: Atlanta
country: United States
facility: Emory Department of Urology, The Emory Clinic Inc, Emory University Hospital
state: Georgia
city: Atlanta
country: United States
facility: American Red Cross
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Overland Park
country: United States
facility: Kansas City Urology Care
state: Kansas
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Baltimore
country: United States
facility: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Clinic
state: Massachusetts
city: Troy
country: United States
facility: Michigan Institute of Urology
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Omaha
country: United States
facility: GU Research Center, LLC
state: Nebraska
city: Hackensack
country: United States
facility: John Theurer Cancer Center, Hackensack University Medical Center
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: NYU Clinical Cancer Center, NYU Langone Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine Department of Urology
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Oneida
country: United States
facility: Associated Medical Professionals of NY, PLLC
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Syracuse
country: United States
facility: Associated Medical Professionals of New York, PLLC
state: New York
city: Chapel Hill
country: United States
facility: UNC Health Care, NC Cancer Hospital
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: TriState Urologic Services PSC, Inc. dba TUG Research
state: Ohio
city: Cincinnati
country: United States
facility: Hoxworth Blood Center
state: Ohio
city: Cincinnati
country: United States
facility: Jewish Hospital
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center, James Cancer Hospital, Martha Morehouse Medical Plaza, Ohio State University Dept of Urology
state: Ohio
city: Tulsa
country: United States
facility: Urologic Specialists of Oklahoma
state: Oklahoma
city: Beaverton
country: United States
facility: OHSU Knight Cancer Institute Hematology Oncology
state: Oregon
city: Portland
country: United States
facility: Providence Medical Center
state: Oregon
city: Springfield
country: United States
facility: Oregon Urology Institute
state: Oregon
city: Bryn Mawr
country: United States
facility: Urology Health Specialists, LLC
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Urology Associates, P.C.
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Norfolk
country: United States
facility: Sentara Leigh Hospital
state: Virginia
city: Virginia Beach
country: United States
facility: Urology of Virginia, PLLC
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Seattle
country: United States
facility: UW Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center
state: Wisconsin
Study officials:
affiliation: Valeant Pharmaceuticals North America LLC
name: Robert Israel, MD
role: STUDY_DIRECTOR
References: