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Phase II Neoadjuvant Doxorubicin and Cyclophosphamide -> Docetaxel With Lapatinib in Stage II/III Her2Neu+ Breast Cancer

This study is currently recruiting participants.
Verified by Stanford University, July 2008

Sponsors and Collaborators: Stanford University
GlaxoSmithKline
Sanofi-Aventis
Information provided by: Stanford University
ClinicalTrials.gov Identifier: NCT00404066
  Purpose

This trial combines dose dense chemotherapy with Doxorubicin and Cyclophosphamide (AC) followed by standard every 3 week docetaxel and GW572016 for neoadjuvant treatment of her2neu positive stage II/III breast cancer. GW572016 or Lapatinib, the investigational agent, acts as a duel inhibitor of both epidermal growth factor receptor (EGFR) and ErbB-2 (Her2/neu) tyrosine kinase activity. EGFR and ErbB2 receptors are frequently over-expressed or altered in human cancers including breast cancer. This study plans to determine the antitumor activity of this regimen and its effectiveness of preventing tumor growth and spread.


Condition Intervention Phase
Breast Cancer
Drug: Lapatinib
Drug: Doxorubicin
Drug: Cyclophosphamide
Drug: Docetaxel
Phase II

Genetics Home Reference related topics:   breast cancer   

MedlinePlus related topics:   Breast Cancer    Cancer   

ChemIDplus related topics:   Doxorubicin    Doxorubicin hydrochloride    Cyclophosphamide    Docetaxel    Lapatinib    Lapatinib Ditosylate    Trastuzumab   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment
Official Title:   Phase II Neoadjuvant Chemotherapy Trial in Clinical Stage II/III Her2Neu Positive Breast Cancer With Sequential AC"³Docetaxel With Concurrent Dual EGFR Kinase Blockade by GW572016 (Lapatinib) Followed by 1 Year Adjuvant Trastuzumab

Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Pathologic complete response

Secondary Outcome Measures:
  • Radiological complete response
  • Rate of breast conserving surgery
  • Side effects and toxicity profile of Docetaxel and GW572016 (Lapatinib)
  • Disease free survival

Estimated Enrollment:   71
Study Start Date:   October 2006

Detailed Description:

This trial combines dose dense chemotherapy with Doxorubicin and Cyclophosphamide (AC) followed by standard every 3 week docetaxel and GW572016 for neoadjuvant treatment of her2neu positive stage II/III breast cancer. GW572016 or Lapatinib, the investigational agent, acts as a duel inhibitor of both epidermal growth factor receptor (EGFR) and ErbB-2 (Her2/neu) tyrosine kinase activity. EGFR and ErbB2 receptors are frequently over-expressed or altered in human cancers including breast cancer. This study plans to determine the antitumor activity of this regimen and its effectiveness of preventing tumor growth and spread.

The primary objective of the study is to improve pathological complete response rates with the addition of dual EGFR blockade. Neoadjuvant chemotherapy which achieves pathologic complete responses (pCR) has been shown to predict improved long-term survival and serves as a surrogate for clinical outcome. By using this primary endpoint we can obtain statistical data with smaller patient numbers and at a lower overall cost. Additionally, we hope to correlate clinical and radiologic outcomes with gene expression data.

  Eligibility
Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Criteria

Inclusion Criteria:- Women with histologically confirmed Her2neu positive breast cancer. Patients are considered Her2Neu positive by either Immunohistochemistry (IHC) 3+ or Fluorescence In Situ Hybridization (FISH)+

  • Stage II/III breast cancer including any large primary tumor (> 2 cm), tumors of any size associated with skin or chest wall involvement, tumors of any size with axillary lymph node involvement, (T2-T4, N0-N2) and those with ipsilateral subclavicular or supraclavicular lymph nodes).
  • At least one bidimensional, measurable indicator lesion. All sites of disease should be noted and followed. Baseline measurements and evaluations of tumor must be done within 3 weeks prior to initiation of treatment.
  • Patients must be between 18 and 70 years of age
  • ECOG performance status 2/ Karnofsky > 60% at screening and on the first day of treatment.
  • Informed consent must be obtained prior to registration.
  • Cardiac ejection fraction within the institutional range of normal as measured by MUGA scan. Note that baseline and on treatment scans should be performed using the same modality and preferably at the same institutions
  • Patients must have normal organ and marrow function as defined below:

    • Hematologic (minimal values)

      1. Absolute neutrophil count > 1,500/mm3
      2. Hemoglobin > 8.0 g/dl
      3. Platelet count > 100,000/mm^3
    • Creatinine within normal institutional limits
    • Hepatic

      1. Total Bilirubin equal to or less than ULN
      2. AST and ALT and Alkaline Phosphatase must be within the range allowing for eligibility.
      3. In determining eligibility the more abnormal of the two values (AST or ALT) should be used.
  • Eligibility of patients receiving medications or substances known to affect, or with the potential to affect the activity or pharmacokinetics of GW572016 will be determined following review of their use by the Principal Investigator

    • Antacid use is prohibited 1 hour before and 1 hour after GW572016 dosing.
    • All herbal (alternative) medicines are prohibited. In addition please see section 6.6 of the protocol regarding medications that are prohibited during the administration of GW572016 and for the duration of GW572016.
  • The effects of GW572016 on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Must have negative pregnancy test if of child bearing years.
  • Peripheral neuropathy: must be < grade 1
  • Able to swallow and retain oral medication Exclusion Criteria:- Evidence of disease outside the breast or chest wall, except for ipsilateral axillary , supraclavicular, or infraclavicular lymph nodes.
  • Prior chemotherapy, immunotherapy, or hormonal therapy for breast cancer.
  • More than 3 months between histologic diagnosis and registration on this study.
  • History of other malignancy within the last five years, except curatively treated basal cell carcinoma of the skin or carcinoma in situ of the cervix.
  • Psychological, familial, sociological or geographical conditions which do not permit weekly medical follow-up and compliance with the study protocol. Patients who are medically unstable, including but not limited to active infection, acute hepatitis, deep vein thrombosis requiring anticoagulant therapy, gastrointestinal bleeding, uncontrolled hypercalcemia, uncontrolled diabetes, dementia, seizures, superior vena cava syndrome, and patients whose circumstances do not permit completion of the study or the required follow-up.
  • Patients who have congestive heart failure, abnormal LVEF, angina pectoris, uncontrolled cardiac arrhythmias, or other significant heart disease, or who have had a myocardial infarction within the past year.
  • Pregnant or lactating females, or females of childbearing potential not employing adequate contraception.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to GW572016.
  • HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with GW572016. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated.
  • Patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis).
  • Patients with a history of severe hypersensitivity reaction to Taxotere® or other drugs formulated with polysorbate 80.
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00404066

Locations
United States, California
Stanford University School of Medicine     Recruiting
      Stanford, California, United States, 94305
      Contact: Mary Chen     650-723-8686     mmjchen@stanford.edu    
      Contact: Cancer Clinical Trials Office     (650) 498-7061        
      Principal Investigator: Dr. Ellie Guardino MD/PhD            
      Sub-Investigator: Robert W Carlson            

Sponsors and Collaborators
Stanford University
GlaxoSmithKline
Sanofi-Aventis

Investigators
Principal Investigator:     Dr. Ellie Guardino MD/PhD     Stanford University    
  More Information


Study ID Numbers:   BRSADJ0002, 96692, BRSADJ0002, NCT00404066
First Received:   November 22, 2006
Last Updated:   July 22, 2008
ClinicalTrials.gov Identifier:   NCT00404066
Health Authority:   United States: Institutional Review Board;   United States: Food and Drug Administration

Study placed in the following topic categories:
Docetaxel
Skin Diseases
Trastuzumab
Breast Neoplasms
Lapatinib
Cyclophosphamide
Doxorubicin
Breast Diseases

Additional relevant MeSH terms:
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Antibiotics, Antineoplastic
Protein Kinase Inhibitors
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents

ClinicalTrials.gov processed this record on September 23, 2008




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