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Docetaxel and Lapatinib With or Without Combination Chemotherapy or Docetaxel and Trastuzumab With Combination Chemotherapy in Treating Women With Locally Advanced, Inflammatory, or Resectable Breast Cancer
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), December 2008
Sponsored by: European Organization for Research and Treatment of Cancer
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00450892
  Purpose

RATIONALE: Drugs used in chemotherapy, such as docetaxel, fluorouracil, epirubicin, and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving these treatments before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving trastuzumab after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of docetaxel and lapatinib when given with or without combination chemotherapy and to see how well they work in treating women with locally advanced, inflammatory, or resectable breast cancer.


Condition Intervention Phase
Breast Cancer
Drug: cyclophosphamide
Drug: docetaxel
Drug: epirubicin hydrochloride
Drug: fluorouracil
Drug: lapatinib ditosylate
Drug: trastuzumab
Procedure: adjuvant therapy
Procedure: biopsy
Procedure: conventional surgery
Procedure: fluorescence in situ hybridization
Procedure: immunohistochemistry staining method
Procedure: laboratory biomarker analysis
Procedure: neoadjuvant therapy
Procedure: pharmacological study
Procedure: proteomic profiling
Procedure: reverse transcriptase-polymerase chain reaction
Phase I
Phase II

Genetics Home Reference related topics: breast cancer
MedlinePlus related topics: Breast Cancer Cancer
Drug Information available for: Cyclophosphamide Docetaxel Fluorouracil Lapatinib Lapatinib Ditosylate Epirubicin hydrochloride Epirubicin Trastuzumab
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Open Label
Official Title: A Phase I-II Study of Lapatinib and Docetaxel as Neoadjuvant Treatment for HER-2 Positive Locally Advanced/Inflammatory or Large Operable Breast Cancer

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Dose-limiting toxicity during course 1 of phase I and course 4 of the bridge step of phase I [ Designated as safety issue: Yes ]
  • Maximum tolerated dose (MTD) of docetaxel and lapatinib ditosylate (Phase I) [ Designated as safety issue: Yes ]
  • MTD and dose intensity of docetaxel and lapatinib ditosylate in combination with fluorouracil, epirubicin hydrochloride, and cyclophosphamide (Phase I) [ Designated as safety issue: Yes ]
  • Pathological complete response rate (Phase II) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in apoptosis and proliferation markers (i.e., PTEN mutation and function, pAkt, mTOR, and associated proteins) (Phase I) [ Designated as safety issue: No ]
  • Correlation of drug exposure with adverse events or biological modifications (Phase I) [ Designated as safety issue: Yes ]
  • Safety and tolerability as defined by CTCAE v 3.0 (Phase II) [ Designated as safety issue: Yes ]
  • Response rate as defined by RECIST criteria in patients with measurable disease (Phase II) [ Designated as safety issue: No ]
  • Pharmacodynamics (Phase II) [ Designated as safety issue: No ]

Estimated Enrollment: 114
Study Start Date: February 2007
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
  Show Detailed Description

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed invasive breast cancer meeting one of the following criteria:

    • Locally advanced or inflammatory disease

      • Clinical stage T4a-d, any N, M0 OR any clinical stage T, N2-3 (ipsilateral supraclavicular nodes), M0 disease
      • OR cT3cN0,1 any estrogen receptor (ER)
      • OR cT2cN1 any ER
      • Or cT2cN0 ER-negative
  • HER2-positive disease by immunohistochemistry, fluorescent in situ hybridization, and/or chromogenic in situ hybridization
  • Bilateral breast cancer is allowed in phase I
  • No bone, liver, or other extensive metastases

    • Minimal lung, skin, or nodal metastases may be allowed at the discretion of the investigator (phase I only)
  • No CNS involvement
  • Hormone receptor status:

    • Estrogen receptor- and/or progesterone receptor-positive or negative tumor

PATIENT CHARACTERISTICS:

  • Female
  • WHO performance status 0-2
  • Hemoglobin > 10.0 g/dL
  • Absolute neutrophil count > 1,500/mm^3
  • Platelet count > 100,000/mm^3
  • Bilirubin < 1.5 times upper limit of normal (ULN)
  • AST and ALT < 3 times ULN
  • Creatinine < 1.5 times ULN
  • No other malignancies within the past 3 years except basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix (phase II)
  • LVEF normal by MUGA or ECHO
  • ECG normal
  • No current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease)
  • No serious cardiac illness or medical condition within the past 6 months including, but not limited to, the following:

    • History of documented congestive heart failure
    • High-risk uncontrolled arrhythmias
    • Angina pectoris requiring antianginal medication
    • Clinically significant valvular heart disease
    • Evidence of transmural infarction on ECG
    • Poorly controlled hypertension, defined as systolic blood pressure (BP) > 180 mm Hg or diastolic BP > 100 mm Hg
  • Able to swallow and retain oral medication
  • No active or uncontrolled infection
  • No other serious illness
  • No malabsorption syndrome
  • No other medical condition (i.e., history of chronic alcohol abuse, hepatitis, HIV, and/or cirrhosis)
  • No psychological, familial, sociological, or geographical condition that would preclude study participation
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception 2 weeks prior to, during, and for 1 month after completion of study treatment

PRIOR CONCURRENT THERAPY:

  • No prior therapy for any cancer, including chemotherapy, radiotherapy, or hormonal therapy for breast cancer (phase I)
  • No prior epidermal growth factor receptor- or HER2-targeted therapy or antibody therapy (phase I)
  • More than 10 days since prior and no concurrent CYP3A4 inducers or inhibitors
  • More than 14 days since prior and no concurrent herbal or dietary supplements
  • No antacids 1 hour before or after lapatinib ditosylate administration
  • No other concurrent investigational therapy or anticancer therapy
  • No concurrent prophylactic antibiotics
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00450892

Locations
United Kingdom, Scotland
Edinburgh Cancer Centre at Western General Hospital Recruiting
Edinburgh, Scotland, United Kingdom, EH4 2XU
Contact: David Cameron, MD     44-131-537-3057     david.cameron@ed.ac.uk    
Sponsors and Collaborators
European Organization for Research and Treatment of Cancer
Investigators
Study Chair: David Cameron, MD Edinburgh Cancer Centre at Western General Hospital
Study Chair: Herve Bonnefoi, MD Hopital Cantonal Universitaire de Geneve
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Publications of Results:
Bonnefoi H, Zaman K, Nobahar M: Lapatax: a phase I study of neoadjuvant lapatinib combined with docetaxel in Her2/neu overexpressing breast cancer (BC) EORTC protocol 10054. [Abstract] A-5112, 2008.

Study ID Numbers: CDR0000536482, EORTC-10054, GSK-EORTC-10054, EUDRACT-2006-000864-94
Study First Received: March 20, 2007
Last Updated: December 23, 2008
ClinicalTrials.gov Identifier: NCT00450892  
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
inflammatory breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer

Study placed in the following topic categories:
Docetaxel
Inflammatory breast cancer
Skin Diseases
Fluorouracil
Trastuzumab
Breast Neoplasms
Lapatinib
Cyclophosphamide
Epirubicin
Breast Diseases

Additional relevant MeSH terms:
Antimetabolites
Antimetabolites, Antineoplastic
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 January 14, 2009