Neoadjuvant Herceptin for Ductal Carcinoma In Situ of the Breast

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00496808
First received: July 3, 2007
Last updated: April 19, 2012
Last verified: April 2012
  Purpose

Primary Objectives:

  • To determine the effect of a single dose of Herceptin (trastuzumab) on the proliferation rate of Her-2/neu over-expressing ductal carcinoma in situ (DCIS)
  • To evaluate the effect of a single dose of Herceptin on the apoptotic index of Her-2/neu over-expressing DCIS

Condition Intervention
Ductal Carcinoma In Situ
Drug: Herceptin (Trastuzumab)

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Neoadjuvant Herceptin for Ductal Carcinoma In Situ of the Breast

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Percent Change in Proliferation as Measured by Ki-67 [ Time Frame: Before and after single dose of Herceptin approximately 21 days before surgery for ductal carcinoma in situ (DCIS), up to 4 weeks ] [ Designated as safety issue: No ]
    Percent Change in Proliferation as measured by Ki-67 (% nuclei stained). Comparison of proliferation rates of Her-2/neu overexpressing cells before and after treatment with Herceptin per Participant where absolute change defined as difference of increase/decrease. Proliferation rate evaluated by immunohistochemistry using paraffin-embedded sections and monoclonal antibody for ki-67.

  • Number of Participants Achieving Documented Change in Proliferation [ Time Frame: Before and after single dose of Herceptin approximately 21 days before DCIS surgery, up to 4 weeks ] [ Designated as safety issue: No ]
    Proliferation rate and apoptotic index measured on core biopsy specimen and resection specimen from each participants. To compare Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and CD4+ T-cell response in each participant observed at pre- and post-treatment times, paired analysis was performed using Student's t-test. Nonparametric Wilcoxon rank sum test was used to compare data between groups.


Secondary Outcome Measures:
  • Mean Percent of Ki-67 [ Time Frame: Before and after single dose of Herceptin approximately 21 days before DCIS surgery, up to 4 weeks ] [ Designated as safety issue: No ]
    Mean percent of Ki-67 (% nuclei stained) at immunohistochemical staining performed for biomarkers. Tissue sections from diagnostic core biopsy tissue that contains DCIS before treatment and from corresponding tissues that contain DCIS from the surgical resection obtained after a single dose of Herceptin.


Enrollment: 69
Study Start Date: March 2005
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Herceptin
8 mg/kg intravenously (IV) Over 90 Minutes
Drug: Herceptin (Trastuzumab)
8 mg/kg IV Over 90 Minutes
Other Name: Trastuzumab

Detailed Description:

Herceptin (Trastuzumab) stops or slows the growth of certain breast cancer cells by blocking the chemical signals they need to grow.

As part of your standard care for DCIS, you will have a complete routine physical exam, a mammogram of both breasts, and blood (about 2 tablespoons) will be drawn for routine tests. Some of your leftover breast biopsy tissue will be tested for Her-2/neu expression. Blood will be drawn (about 2-6 teaspoons) to check if your bone marrow (red blood cells), kidney, and liver are functioning well enough to have this treatment. Women who are able to have children must have a negative blood pregnancy test before starting treatment.

If you are eligible to take part in this study, you will receive one dose of trastuzumab at least 2 weeks before your surgery. The dose of trastuzumab will be given intravenously (through a needle in a vein in your arm) as a steady infusion over 90 minutes, on an outpatient basis. You will be checked during the infusion and for 1 hour after it is completed.

You will have routine surgery for DCIS (either segmental mastectomy, mastectomy with or without reconstruction, and possible sentinel lymph node biopsy) approximately 14 to 28 days after being given Herceptin. If a segmental mastectomy was performed as part of our standard practice you will be evaluated by a radiation oncologist following surgery. After your surgery, patients will also be evaluated by a breast medical oncologist to determine if any additional standard therapy is needed.

Tissue that is left over from the original breast biopsy and surgery will be tested for various biomarkers (substances which indicate the severity or spread of cancer), cancer growth rate, and apoptotic index (cell death rate).

This is an investigational study. The FDA has approved trastuzumab for the treatment of breast cancer. Up to 71 patients will take part in this study. All will be enrolled at M. D. Anderson.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. All patients with histologic confirmation of DCIS (TisN0M0) that is Her-2/neu 3+ positive by immunohistochemistry (IHC) and/or positive for Her-2 gene amplification by fluorescence in situ hybridization (FISH) will be eligible for the study.
  2. Patients must sign informed consent indicating that they are aware of the investigational nature of the study, in keeping with institutional policy.
  3. Those patients with history of other contralateral non-invasive and invasive breast and non-breast malignancies are eligible to participate unless they have previously received a doxorubicin dose of more than 400 mg/m2.
  4. All patients should have adequate bone marrow function, as defined by peripheral granulocyte count of > 1,500/mm3, and platelet count > 100,000 mm3. Patients must have adequate liver function, with bilirubin within normal laboratory values. In addition, patients should have adequate renal function, defined as serum creatinine < 2.0 mg/dl.
  5. Patients with intact primary tumors will be eligible for this study. Patients who have had their diagnostic biopsy at an outside facility but still have measurable disease on presentation will be eligible.
  6. Patients with history of cardiac arrhythmia will be eligible for study after being seen by cardiology and deemed good candidates for participation.
  7. Women of child bearing potential must have a negative urine or serum pregnancy test.

Exclusion Criteria:

  1. Patients with a current known invasive breast cancer are not eligible for this study.
  2. All patients who are Her-2/neu negative will be ineligible for the study.
  3. Patients with history of congestive heart failure will be excluded.
  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: NCT00496808

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Henry Kuerer, MD, PhD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00496808     History of Changes
Other Study ID Numbers: 2004-0701
Study First Received: July 3, 2007
Results First Received: June 27, 2011
Last Updated: April 19, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Ductal Carcinoma In Situ
Breast Cancer
Herceptin
Trastuzumab
DCIS

Additional relevant MeSH terms:
Carcinoma
Carcinoma in Situ
Carcinoma, Intraductal, Noninfiltrating
Breast Neoplasms
Carcinoma, Ductal, Breast
Carcinoma, Ductal
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Neoplasms, Ductal, Lobular, and Medullary
Neoplasms by Site
Breast Diseases
Skin Diseases
Trastuzumab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014