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

Urothelial Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01353222
• Other study ID #: N10-1
• Status: Completed
• Phase: Phase 2
• First received: May 4, 2011
• Last updated: February 29, 2016
• Start date: June 2011
• Est. completion date: July 2015

Study information

• Verified date: February 2016
• Source: Dendreon
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Description:

This is a multicenter, open-label, Phase 2 study. Subjects will be randomized to either the investigational product, DN24-02, or to standard of care. The purpose of this study is to compare the length of survival between these 2 groups of subjects. Other purposes of the study are to learn about the safety of DN24-02, to learn if it delays the time until urothelial cancer recurs, and to learn if the immune system responds to treatment with DN24-02. All subjects will be followed for this study for the remainder of their lives.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 142
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histopathologic evidence of urothelial carcinoma at high risk of recurrence.

• Radical surgical resection was performed = 84 days (12 weeks) prior to registration.

• No evidence of residual disease or metastasis on 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 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 have 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) 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 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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Urothelial Carcinoma

Intervention

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.

Other:
• Standard of Care
Standard of care

Locations

Country	Name	City	State
United States	American Red Cross	Atlanta	Georgia
United States	Emory Department of Urology, The Emory Clinic Inc, Emory University Hospital	Atlanta	Georgia
United States	University of Colorado, Anschutz Cancer Pavilion	Aurora	Colorado
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	OHSU Knight Cancer Institute Hematology Oncology	Beaverton	Oregon
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Urology Health Specialists, LLC	Bryn Mawr	Pennsylvania
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Lahey Clinic	Burlington	Massachusetts
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 Chicago Medical Center	Chicago	Illinois
United States	Hoxworth Blood Center	Cincinnati	Ohio
United States	Jewish Hospital	Cincinnati	Ohio
United States	TriState Urologic Services PSC, Inc. dba TUG Research	Cincinnati	Ohio
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	The Urology Center of Colorado	Denver	Colorado
United States	City of Hope Medical Center	Duarte	California
United States	Duke University	Durham	North Carolina
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	Urological Research Network	Hialeah	Florida
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	USC/Norris Comprehensive Cancer Center	Los Angeles	California
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	University of Miami Cancer Center	Miami	Florida
United States	University of Minnesota	Minneapolis	Minnesota
United States	Urology Associates, P.C.	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Memorial Sloan Kettering	New York	New York
United States	Mount Sinai School of Medicine	New York	New York
United States	Mount Sinai School of Medicine Department of Urology	New York	New York
United States	NYU Clinical Cancer Center, NYU Langone Medical Center	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Sentara Leigh Hospital	Norfolk	Virginia
United States	GU Research Center, LLC	Omaha	Nebraska
United States	Associated Medical Professionals of NY, PLLC	Oneida	New York
United States	Kansas City Urology Care	Overland Park	Kansas
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Mayo Clinic Hospital	Phoenix	Arizona
United States	Providence Medical Center	Portland	Oregon
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester Medical Center	Rochester	New York
United States	Genesis Research	San Diego	California
United States	Mayo Clinic Arizona	Scottsdale	Arizona
United States	UW Medical Center	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Oregon Urology Institute	Springfield	Oregon
United States	Stanford University Hospital	Stanford	California
United States	Associated Medical Professionals of New York, PLLC	Syracuse	New York
United States	H. Lee Moffitt Cancer Center & Research Institute, Inc.	Tampa	Florida
United States	Michigan Institute of Urology	Troy	Michigan
United States	Urologic Specialists of Oklahoma	Tulsa	Oklahoma
United States	Urology of Virginia, PLLC	Virginia Beach	Virginia
United States	University of Kansas Cancer Center	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Dendreon

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate overall survival following administration of DN24-02		Subjects will be followed from baseline through the remainder of their lives or until study completion (approximately 5 years)	No
Secondary	Evaluate disease-free survival following administration of DN24-02		Baseline through disease recurrence or study completion (approximately 5 years), whichever occurs first	No
Secondary	Evaluate the safety of DN24-02	Safety will be assessed by summarizing adverse events, laboratory evaluations, vital signs, cardiac function, and physical examination findings.	Baseline through study completion (approximately 5 years)	Yes
Secondary	Evaluate the magnitude of immune response induced by administration of DN24-02	Subjects will be evaluated for cellular and humoral immune responses to HER2 following periodic blood draws.	Baseline through disease recurrence	No
Secondary	Evaluate the magnitude of cumulative CD54 upregulation following administration of DN24-02		Prior to infusion, approximately 4-8 weeks after randomization	No