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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Dendreon
ClinicalTrials.gov Identifier:
NCT01353222
First received: May 4, 2011
Last updated: January 20, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Urothelial Carcinoma
Biological: DN24-02
Other: Standard of Care
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Phase 2, Open-label Study Evaluating DN24-02 as Adjuvant Therapy in Subjects With High Risk HER2+ Urothelial Carcinoma

Resource links provided by NLM:


Further study details as provided by Dendreon:

Primary Outcome Measures:
  • Evaluate overall survival following administration of DN24-02 [ Time Frame: Subjects will be followed from baseline through the remainder of their lives or until study completion (approximately 5 years) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Evaluate disease-free survival following administration of DN24-02 [ Time Frame: Baseline through disease recurrence or study completion (approximately 5 years), whichever occurs first ] [ Designated as safety issue: No ]
  • Evaluate the safety of DN24-02 [ Time Frame: Baseline through study completion (approximately 5 years) ] [ Designated as safety issue: Yes ]
    Safety will be assessed by summarizing adverse events, laboratory evaluations, vital signs, cardiac function, and physical examination findings.

  • Evaluate the magnitude of immune response induced by administration of DN24-02 [ Time Frame: Baseline through disease recurrence ] [ Designated as safety issue: No ]
    Subjects will be evaluated for cellular and humoral immune responses to HER2 following periodic blood draws.

  • Evaluate the magnitude of cumulative CD54 upregulation following administration of DN24-02 [ Time Frame: Prior to infusion, approximately 4-8 weeks after randomization ] [ Designated as safety issue: No ]

Estimated Enrollment: 180
Study Start Date: June 2011
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
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.
Standard of Care Other: Standard of Care
Standard of care

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01353222

  Show 60 Study Locations
Sponsors and Collaborators
Dendreon
Investigators
Study Chair: Candice McCoy Dendreon
  More Information

No publications provided

Responsible Party: Dendreon
ClinicalTrials.gov Identifier: NCT01353222     History of Changes
Other Study ID Numbers: N10-1
Study First Received: May 4, 2011
Last Updated: January 20, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Dendreon:
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

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on July 29, 2014