Evaluate Trastuzumab Plus Standard Chemotherapy Given Before Surgery in Breast Cancer Patients With Low HER 2 Expression

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by University of Kansas
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
University of Kansas
ClinicalTrials.gov Identifier:
NCT00944047
First received: July 16, 2009
Last updated: December 30, 2013
Last verified: December 2013
  Purpose

The purpose of this study is to find out if there is a benefit of adding Herceptin (trastuzumab) to standard chemotherapy in this type of breast cancer.


Condition Intervention Phase
Breast Cancer
Drug: nab-paclitaxel
Drug: trastuzumab
Drug: Doxorubicin
Drug: cyclophosphamide
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Abraxane and Trastuzumab Followed by Dose Dense Doxorubicin and Cyclophosphamide as Neoadjuvant Therapy in Invasive Breast Cancer With Low HER2 Expression (1+ or 2+ by IHC)

Resource links provided by NLM:


Further study details as provided by University of Kansas:

Primary Outcome Measures:
  • Pathologic Complete Response [ Time Frame: 22 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Assessment of cardiac safety by comparing left ventricular ejection fraction by echocardiogram from baseline to completion of treatment and assessment of reduction in primary tumor size response after first two cycles of chemotherapy with pCR rate. [ Time Frame: 22 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: July 2009
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Nab-paclitaxel, trastuzumab, doxorubicin, cyclophosphamide
Drug: nab-paclitaxel
100 MG/M2 IV over 30 minutes once a week for 12 weeks
Other Name: Abraxane
Drug: trastuzumab
4 MG loading dose followed by 2 MG/KG every week for a total of 12 weeks
Other Name: Herceptin
Drug: Doxorubicin
60 MG/M2 every two weeks for a total of 4 cycles
Other Name: Adriamycin
Drug: cyclophosphamide
600 MG/M2 every 2 weeks for 4 cycles (administered with Doxorubicin above)
Other Name: Cytoxan

Detailed Description:

Neoadjuvant (primary) chemotherapy refers to chemotherapy given before surgery. Neoadjuvant chemotherapy has a number of potential advantages including increasing the chances for breast preservation at the time of surgery as well as it may improve the local control of the cancer. Several national breast cancer studies have shown that neoadjuvant chemotherapy was equal to chemotherapy given following surgery.

A standard treatment for stage II or Stage III invasive breast cancer with low HER2 expression is combination chemotherapyAdriamycin, Cytoxan,followed by a Taxane: given either before or after surgery), followed by surgery +/- radiation therapy.

The main purpose of chemotherapy however is to reduce the risk of recurrence of cancer and also make surgery more successful. HER2 is a receptor located on the surface of some cells. This receptor plays a role in regulating the growth of the cell, in addition to the growth of tumors. High levels of the HER2 receptor may predict those women who benefit from treatment with agents such as Herceptin that target HER2. Herceptin (Trastuzumab) is a drug that is effective both alone and in combination with standard chemotherapy. There is some data to suggest that patients whose tumors have low expression of the HER2 protein and are normal by FISH may also receive benefit from Herceptin.

  Eligibility

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

Inclusion Criteria:

  • Female patient ≥ 18 years of age
  • Histologically proven stage II or III adenocarcinoma of the breast
  • Must be candidate for neoadjuvant treatment (Tumor size ≥ 2 cm, T2, T3, T4 and/or clinical N1 or N2).
  • HER-2/neu 1+ or 2+ by immunohistochemistry
  • Must have operable tumor.
  • Performance status of 2 or better per SWOG criteria
  • LVEF ≥ 55% by echocardiogram performed within 4 weeks prior to treatment initiation
  • If patient of childbearing potential, pregnancy test is negative
  • Patients with reproductive potential must use an effective method to avoid pregnancy for the duration of the trial.
  • Adequate bone marrow function: ANC > 1500/mm3, platelet count > 100,000/mm3, and hemoglobin > 9 g/dL
  • Adequate kidney function: serum creatinine of < 1.5mg/dl and/or creatinine clearance of > 60 mL/min
  • Adequate hepatic function: transaminases < 2.5 x upper limit of normal and total bilirubin < 1.5 mg/dL
  • Must be informed of the investigational nature of the study and must sign an informed consent in accordance with the institutional rules.
  • Pretreatment lab values must be performed within 14 days of patient registration, and other baseline studies (with the exception of mammogram) must be performed within 30 days of patient registration.

EXCLUSION CRITERIA:

  • Patient with metastatic breast cancer.
  • Women with tumors that are HER-2 neu 0+ or 3+ by immunohistochemistry
  • Women with HER 2 FISH amplified tumors (FISH ratio >2.2)
  • Patients who have had prior endocrine therapy for > 4 weeks or chemotherapy for this breast cancer will be excluded.
  • Locally advanced, inoperable tumors will be excluded.
  • The presence of any other medical or psychiatric disorder that, in the opinion of the treating physician, would contraindicate the use of drugs in this protocol or place the subject at undue risk for treatment complications.
  • History of significant cardiac disease, cardiac risk factors or uncontrolled arrhythmias
  • Ejection fraction < 55%
  • Pregnancy or lactation
  • Patients with inadequate laboratory values (as defined above) are excluded from study.
  • Patients with NCI common toxicity criteria (CTC) grade 2 or greater peripheral neuropathy are excluded from study.
  • Patients with active infection are excluded from study.
  • Patients with concomitant or previous malignancies within the last 5 years, are excluded from the study. Exceptions include: adequately treated basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, and ductal carcinoma in situ (DCIS).
  • Patients with emotional limitations are excluded from study.
  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: NCT00944047

Contacts
Contact: Stella Baccaray, RN 913-588-2937 sbaccaray@kumc.edu

Locations
United States, Kansas
Hays Medical Center Recruiting
Hays, Kansas, United States, 67601
Contact: Anne O'Dea, MD    785-623-5774    anneodea@haysmed.com   
Contact: January Fields-Meehan, MD    785-623-5774      
Sub-Investigator: Anne O'Dea, MD         
Sub-Investigator: January Fields-Meehan, MD         
University of Kansas Medical Center Cancer Center Recruiting
Kansas City, Kansas, United States, 66205
Sub-Investigator: Priyanka Sharma, MD         
Sub-Investigator: Carol Fabian, MD         
Sponsors and Collaborators
University of Kansas
Celgene Corporation
Investigators
Principal Investigator: Qamar Khan, MD University of Kansas Medical Center Cancer Center
  More Information

No publications provided

Responsible Party: University of Kansas
ClinicalTrials.gov Identifier: NCT00944047     History of Changes
Other Study ID Numbers: 11368
Study First Received: July 16, 2009
Last Updated: December 30, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Kansas:
invasive breast cancer
HER2
primary breast cancer
neo-adjuvant therapy
Trastuzumab
Nab-paclitaxel

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Cyclophosphamide
Doxorubicin
Liposomal doxorubicin
Paclitaxel
Trastuzumab
Alkylating Agents
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Tubulin Modulators

ClinicalTrials.gov processed this record on October 23, 2014