DC Vaccine for Patients With Ductal Carcinoma In Situ (DCIS6)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by University of Pennsylvania
Sponsor:
Information provided by (Responsible Party):
Brian Czerniecki, University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT02061332
First received: February 10, 2014
Last updated: February 11, 2014
Last verified: February 2014
  Purpose

Women who are diagnosed with Her-2/neu over-expressing DCIS will receive DC1 vaccines by intranodal, intralesional, or both routes of administration. The primary objective will be safety and administration with secondary objectives of immune activation and clinical response.


Condition Intervention Phase
Breast Cancer
DCIS
Biological: HER-2 Pulsed Dendritic cell Vaccine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Randomized Trial of HER-2/Neu Pulsed DC1 Vaccine for Patients With DCIS

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • Blood Pressure [ Time Frame: up to 60 minutes post vaccine ] [ Designated as safety issue: Yes ]
    Blood pressure will be obtained just prior to the vaccination then, every 15 minutes for the first hour after the dose is given.

  • Temperature [ Time Frame: up to 60 minutes post vaccine ] [ Designated as safety issue: Yes ]
    Temperature will be obtained just prior to the vaccination then, every 15 minutes for the first hour after the dose is given.

  • Pulse [ Time Frame: up to 60 minutes post vaccine ] [ Designated as safety issue: Yes ]
    Pulse will be obtained just prior to the vaccination then, every 15 minutes for the first hour after the dose is given.


Secondary Outcome Measures:
  • Immune Response [ Time Frame: 6-8 weeks ] [ Designated as safety issue: No ]
    Subjects will undergo leukapheresis after completion of 6 vaccines and 3 boost vaccines for the purpose of obtaining lymphocytes and monocytes for in vitro immunologic testing.

  • Mammogram [ Time Frame: 6-8 weeks ] [ Designated as safety issue: No ]
    All subjects will have a post-vaccine bilateral mammogram to evaluate response to vaccination. Mammograms will be performed within two weeks after the 6th vaccination.

  • MRI [ Time Frame: 6-8 weeks ] [ Designated as safety issue: No ]
    All subjects will have a post-vaccine bilateral breast MRI to evaluate response to vaccination. MRIs will be performed within two weeks after the 6th vaccination.


Estimated Enrollment: 54
Study Start Date: July 2009
Estimated Study Completion Date: July 2019
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intranodal Vaccine
An ultrasound device (probe) will be placed over the area of the groin or armpit. The vaccine needle will then be placed under the probe, and guided by the ultrasound machine to the groin lymph nodes or axillary nodes. You will be given a HER-2 pulsed dendritic cell vaccine in two different groin lymph nodes or axillary nodes per visit. Each dose will consist of 1.0-2.0 x 107 cells and will be injected into 1-2 different groin lymph nodes or axillary nodes.
Biological: HER-2 Pulsed Dendritic cell Vaccine
6 weekly HER-2 pulsed dendritic cell vaccines will be administered to subjects in each of the 3 arms.
Experimental: Intralesional Vaccine
The HER-2 pulsed dendritic cell vaccine will be directly injected into the quadrant of the breast affected with DCIS. The location will be determined by referring to the patient's mammogram. Each dose will consist of 1.0-2.0 x 107 cells and will be injected into the quadrant of the breast affected with DCIS.
Biological: HER-2 Pulsed Dendritic cell Vaccine
6 weekly HER-2 pulsed dendritic cell vaccines will be administered to subjects in each of the 3 arms.
Experimental: Intranodal + Intralesional Vaccine
You will be given a HER-2 pulsed dendritic cell vaccine in two different groin lymph nodes or axillary nodes and the quadrant of the breast affected with DCIS. An ultrasound device (probe) will be placed over the groin or armpit. The vaccine needle will be placed under the probe, and guided by the ultrasound machine to the groin lymph nodes or axillary nodes. The intralesional vaccine will be directly injected into the quadrant of the breast affected with DCIS. The location will be determined by referring to the patient's mammogram. Each dose will consist of 1.0-2.0 x 107 cells. Approximately half of the dose will be injected into 1-2 different groin lymph nodes or axillary nodes. The remaining half will be injected into the quadrant of the breast affected with DCIS.
Biological: HER-2 Pulsed Dendritic cell Vaccine
6 weekly HER-2 pulsed dendritic cell vaccines will be administered to subjects in each of the 3 arms.

Detailed Description:

The treatment of patients with DCIS can be individualized and tailored to the type of DCIS and the relative risk of the lesion. HER-2/neu over-expressing DCIS represents a group of patients with significant risk for development of invasive breast cancer. In this proposal we will continue to evaluate the development of type I polarized DC for the treatment of DCIS by evaluating whether further improvements in therapeutic response can be achieved by intratumoral administration of HER-2/neu pulsed DC1 compared with our current intranodal administration. Women who are diagnosed with Her-2/neu over-expressing DCIS with no invasive carcinoma will be eligible for this study. Patients will receive DC1 vaccines by intranodal, intralesional, or both routes of administration. The primary objective will be safety and administration with secondary objectives of immune activation and clinical response. We will also develop a novel assay to monitor ongoing immunity to HER-2/neu, and lastly will begin to develop these vaccines for patients with invasive breast cancer as well. Fifty-four subjects will be randomized to one of three treatment arms: intranodal injection, intralesional injection, or intranodal and intralesional injection of the vaccine. Upon entering this study, the subjects' blood will be drawn in a way that collects only the white blood cells. Subjects then receive six vaccines over a six week period. They will then undergo the standard surgical procedure to remove any remaining DCIS in the breast.

  Eligibility

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

Inclusion Criteria:

  • Age > 18 years.
  • Subjects with biopsy-proven DCIS, DCIS with microinvasion, DCIS with invasive disease under 5 mm, or Paget's Disease of the nipple (DCIS of the nipple) who have not yet received definitive treatment.
  • HER-2/neu positive tumor as determined by >5% of tumor population expressing this marker by immunohistochemical staining 2+ using anti-HER-2/neu verified by Dr. Paul Zhang in the Department of Pathology.
  • Women of childbearing age with a negative pregnancy test documented prior to enrollment.
  • Subjects with ECOG Performance Status Score of 0 or 1 (Appendix D).
  • Subjects willing to use birth control if necessary
  • Subjects who have voluntarily signed a written Informed Consent in accordance with institutional policies after its contents have been fully explained to them.

Exclusion Criteria:

  • Pregnant or lactating females (pregnancy testing to be performed within 7 days prior to administration of first dose of vaccine).
  • Subjects who have had a complete excisional biopsy of their tumor.
  • Subjects with suspicion of invasive disease > 5mm by MRI performed within 2 months of study recruitment.
  • Screen and exclude subjects with positive HIV or hepatitis C at baseline.
  • Subjects with coagulopathies, including thrombocytopenia with platelet count <75,000, INR > 1.5 and partial thromboplastin time > 50 sec
  • Subjects with major cardiac illness MUGA < 50% EF.
  • Subjects with pre-existing medical illnesses or medications which might interfere with the study.
  • Subjects with laboratory tests reflecting ¬> grade 1 toxicity by NCI CTC version 3.0 including CBC, liver function tests, urinalysis, EKG if cannot be corrected on repeat test in 7 days.
  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: NCT02061332

Contacts
Contact: Jeanne Kobilnyk, MBE 215-349-8399 jeanne.kobilnyk@uphs.upenn.edu

Locations
United States, Pennsylvania
Hospital of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Jeanne E Kobilnyk, MBE    215-349-8399    jeanne.kobilnyk@uphs.upenn.edu   
Principal Investigator: Brian J Czerniecki, M.D., Ph.D.         
Sub-Investigator: Harvey Nisenbaum, MD         
Sub-Investigator: Susan Weinstein, MD         
Sub-Investigator: Abass Alavi, MD         
Sub-Investigator: Kevin Fox, MD         
Sub-Investigator: Angela DeMichele, MD, MSCE         
Sub-Investigator: Stephen Hahn, MD         
Sub-Investigator: Paul Zhang, MD, PhD         
Sub-Investigator: Julia Tchou, MD         
Sub-Investigator: Rosemarie Mick, MS         
Sponsors and Collaborators
University of Pennsylvania
Investigators
Principal Investigator: Brian J Czerniecki, M.D., Ph.D. University of Pennsylvania
  More Information

Additional Information:
Publications:
Responsible Party: Brian Czerniecki, Harrington/Rhoades Professor of Surgery, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT02061332     History of Changes
Obsolete Identifiers: NCT00923143
Other Study ID Numbers: 807010, 15107
Study First Received: February 10, 2014
Last Updated: February 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Pennsylvania:
Breast Cancer
DCIS
Immunotherapy
Vaccine
Dendritic Cell

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma in Situ
Carcinoma, Intraductal, Noninfiltrating
Carcinoma, Ductal
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma
Neoplasms, Ductal, Lobular, and Medullary

ClinicalTrials.gov processed this record on August 21, 2014