Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Evaluation of the Addition of Herceptin to Standard Chemotherapy in the Neoadjuvant Setting for Operable Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00038402
Recruitment Status : Completed
First Posted : May 31, 2002
Last Update Posted : July 20, 2012
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Tracking Information
First Submitted Date  ICMJE May 30, 2002
First Posted Date  ICMJE May 31, 2002
Last Update Posted Date July 20, 2012
Study Start Date  ICMJE April 2001
Actual Primary Completion Date November 2004   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 10, 2011)
Number of Participants Achieved Pathological Complete Remission [ Time Frame: Baseline to last treatment cycle (approximately 28 weeks, 4 cycles of 21-day intervals of Taxol and up to 4 cycles of FEC for 3-4 week intervals) ]
Response criteria for Complete Remission defined as disappearance of all clinical evidence of active tumor by clinical evaluation, mammogram and/or ultrasound, and free of all symptoms.
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00038402 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of the Addition of Herceptin to Standard Chemotherapy in the Neoadjuvant Setting for Operable Breast Cancer
Official Title  ICMJE Evaluation of the Addition of Herceptin to Standard Chemotherapy in the Neoadjuvant Setting for Operable Breast Cancer
Brief Summary

The purpose of this study is to evaluate the addition of Herceptin to standard chemotherapy treatment of patients newly diagnosed with operable breast cancer.

Other objectives: 1) to evaluate the potential of this therapy to reduce the size of the tumor and increase the possibility of breast conservative surgery, 2) evaluate the ability of this regimen to prevent recurrence of breast cancer and impact on survival, 3) determine side effect profile with the addition of Herceptin, and 4) evaluate significance of HER2 expression by two different methods.

Detailed Description

Participants will receive Herceptin in addition to chemotherapy with Taxol and FEC. 'FEC' is Fluorouracil, Cyclophosphamide and Epirubicin.

During the first course of therapy Herceptin will be given on day 1 through a needle in a vein over 90 minutes. Participants will then be observed for 1 hour after that for harmful side effects. If none occur, later doses of Herceptin will be given over 30 minutes instead of 90 minutes.

On day 2, participants will be given Taxol again through a needle in a vein over 24 hours. Participants will receive the drugs Decadron (dexamethasone), Benadryl (diphenhydramine) and Tagamet (cimetidine) prior to Taxol treatment to prevent allergic reaction due to Taxol. Participants will be observed for 1 hour after starting Taxol for harmful side effects. If none occur, both Taxol and Herceptin can be given on the same day on subsequent courses. Taxol will be premedicated with the same drugs on subsequent courses.

Participants will receive Herceptin weekly for 24 consecutive weeks. Taxol will be given to participants every 3 weeks for 4 courses.

Participants who get a fever or infection during treatment may be given the drug G-CSF. Granulocyte colony-stimulating factor (G-CSF or GCSF) stimulates the bone marrow to make white blood cells, which fight infections.

After Taxol treatment, all participants will receive the drugs fluorouracil, cyclophosphamide, and epirubicin (FEC) through a plastic tube in a vein. Fluorouracil will be given intravenously (IV) as a short infusion on days 1 and 4. Cyclophosphamide will be given intravenously as a short infusion on day 1. Epirubicin will be given IV on day 1. This FEC treatment will be repeated every 3 weeks for a total of 4 treatments. Participants will continue to receive Herceptin weekly during therapy with FEC.

After all FEC treatment is done and surgery is completed, patients with tumors that are sensitive to hormones will begin taking the drug tamoxifen and/or aromatase inhibitors if the patient is postmenopausal. The drug will be given as a pill once a day for 5 years.

Patients will then have surgery to remove all or part of the breast that has cancer. If there are signs that the lymph nodes in the armpit (axilla) contain cancer, these lymph nodes will be removed. Patients may then receive radiation treatment to the breast area and armpit once a day for six weeks.

During the study, participants will have blood tests once a week during the first course of treatment of both Taxol and FEC. In subsequent courses, blood tests will be done prior to administration of chemotherapy. A mammogram and a sonogram will be obtained after Taxol treatment and after FEC treatment. This will help doctors keep track of the tumor size and decide whether to remove all or part of the breast and nearby lymph nodes.

After the study, participants will return for checkups every 4 months during years 1 and 2, every 6 months during year 3, and once a year after that. At each visit, participants will have a complete exam including blood tests and a chest x-ray. Mammography will be done once a year.

Before the study, participants will have a complete exam including blood tests and a chest x-ray. A mammogram and a sonogram of the breast and armpit will be obtained to record tumor size. Small metal clips will be inserted into the breast to mark the tumor if the tumor is shrinking rapidly in response to therapy; in this way, if the tumor disappears after drug treatment, the surgeon can still remove the tissue around the tumor. Sonography of the liver or a CT scan of the abdomen will also be done. In some participants, 3-4 samples of the breast that has tumor will be taken. The samples will be taken using a biopsy needle. An echocardiogram (heart function test) will be done on every participant at baseline. An echocardiogram will be done after finishing their Taxol chemotherapy and another one after finishing FEC chemotherapy. Copies of the echocardiogram tapes may be sent to the sponsor for review. Women who are able to have children will have a pregnancy test.

After having completed therapy, all patients will have a follow-up evaluation of their heart function (same as baseline) 4 months or greater after last treatment.

This is an investigational study. Taxol and Herceptin and all other drugs used in this study are approved by the U. S. Food and Drug Administration. All patients will be treated in the MD Anderson Cancer Center outpatient clinic.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Drug: Herceptin
    Starting dose of 4 mg/kg by vein, then 2 mg/kg weekly after that until the end of all cycles of neo-adjuvant chemotherapy and during FEC therapy for a total of 24 doses.
    Other Name: Trastuzumab
  • Drug: Taxol
    225 mg/m^2 by vein as a continuous infusion over 24 hours each cycle for a total of 4 cycles.
    Other Name: Paclitaxel
  • Drug: Fluorouracil
    500 mg/m^2 by vein on Days 1 and 4 for 4 cycles at 3-4 week intervals.
  • Drug: Cytoxan
    500 mg/m^2 on Day 1 of each cycle for 4 cycles.
    Other Names:
    • Cyclophosphamide
    • Neosar
  • Drug: Epirubicin
    75 mg/m^2 IV on Day 1 of each cycle for 4 cycles.
Study Arms  ICMJE Experimental: Herceptin + Taxol Followed by FEC
Herceptin starting 4 mg/kg intravenous (IV), then 2 mg/kg weekly for all other cycles neo-adjuvant chemotherapy and during FEC therapy for total 24 doses. Taxol 225 mg/m^2 continuous IV over 24 hours each cycle; Fluorouracil 500 mg/m^2 IV Days 1 at 3-4 week intervals; Cytoxan 500 mg/m^2 IV on Day 1; Epirubicin 75 mg/m^2 IV on Day 1. Four 21-day cycles.
Interventions:
  • Drug: Herceptin
  • Drug: Taxol
  • Drug: Fluorouracil
  • Drug: Cytoxan
  • Drug: Epirubicin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 10, 2011)
74
Original Enrollment  ICMJE
 (submitted: June 23, 2005)
164
Actual Study Completion Date  ICMJE July 2011
Actual Primary Completion Date November 2004   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. All patients with histologic confirmation of invasive, but non-inflammatory carcinoma of the breast with T2-3 (greater than 2 cm), N0-1, M0 will be eligible. Patients with T1N1 (after histological confirmation of nodal disease) will be eligible for the study.
  2. Histologic confirmation of invasive tumor will be done by core needle biopsy. On the tissue obtained, estrogen and progesterone receptors (ER/PR) as well as Her-2/neu (will be determined by immunohistochemistry (IH) and/or fluorescence in situ hybridization (FISH)) and p53 will be done (for research evaluation). Tumor proliferation rate will be evaluable by immunohistochemistry using paraffin-embedded sections and monoclonal antibody for ki-67. Residual tumor tissue will be saved in the tissue bank for further future studies.
  3. All patients who are Her-2/neu positive will be eligible for the study. Her-2/neu positivity for protocol purposes will be determined by IHC and patients with tumors that are 3+ or FISH + will be eligible.
  4. Patients must sign an informed consent indicating that they are aware of the investigational nature of the study, in keeping with institutional policy.
  5. 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 a bilirubin within normal laboratory values. In addition, patients should have adequate renal function, defined as serum creatinine <2.0 mg%.
  6. Patients must have a normal cardiac ejection fraction as determined by baseline echocardiogram. Tape must be saved for review by central cardiologist.
  7. Patients who underwent biopsy outside will be eligible if they had a measurable residual tumor.
  8. Patients with multicentric disease and extensive Ductal Carcinoma in Situ (DCIS) will be eligible for study.
  9. Patients with a history of cardiac arrhythmia will be eligible for study after being cleared by cardiology.

Exclusion Criteria:

  1. Patients with T1N0 disease are not eligible for the study.
  2. Those patients with history of other invasive malignancies will be excluded except non-melanoma skin cancer and non-invasive cervical cancer.
  3. Patients with a history of congestive heart failure will be excluded.
  4. Patients who had surgical therapy prior to referral will be ineligible.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00038402
Other Study ID Numbers  ICMJE ID99-146
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party M.D. Anderson Cancer Center
Study Sponsor  ICMJE M.D. Anderson Cancer Center
Collaborators  ICMJE Genentech, Inc.
Investigators  ICMJE
Principal Investigator: Aman U Buzdar, MD M.D. Anderson Cancer Center
PRS Account M.D. Anderson Cancer Center
Verification Date July 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP