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Phase I/II Study of Neoadjuvant Lapatinib in Breast Cancer

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ClinicalTrials.gov Identifier: NCT00450892
Recruitment Status : Completed
First Posted : March 22, 2007
Last Update Posted : July 7, 2016
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC

Brief Summary:

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 or disease Intervention/treatment Phase
Breast Cancer Drug: docetaxel+lapatinib Drug: docetaxel + trastuzumab Drug: docetaxel + trastuzumab + lapatinib Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 129 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : February 2007
Actual Primary Completion Date : July 2013
Actual Study Completion Date : July 2013

Arm Intervention/treatment
arm 1 Drug: docetaxel+lapatinib
3 cycles of docetaxel (100 mg/m²) + lapatinib (1000 mg/d) followed by 3 cycles of FEC

arm 2 Drug: docetaxel + trastuzumab
3 cycles of docetaxel (100 mg/m²) + trastuzumab weekly schedule followed by 3 cycles of FEC 100

Experimental: arm 3 Drug: docetaxel + trastuzumab + lapatinib

3 cycles of docetaxel (100 mg/m²) + trastuzumab weekly schedule

+lapatinib (1000 mg/d) followed by 3 cycles of FEC 100

Primary Outcome Measures :
  1. Phase I part: Dose limiting toxicity during cycle 1 [ Time Frame: during study ]
  2. Phase II: Pathological complete response rate [ Time Frame: end of study ]

Secondary Outcome Measures :
  1. Phase I: Changes in apoptosis and proliferation markers. [ Time Frame: end of Phase I ]
  2. Phase II: Tolerability, clinical/radiological response rates, breast conserving surgery, pharmacodynamics data [ Time Frame: end of study ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No


  • Histologically confirmed invasive breast cancer meeting the following criteria:

    • Phase I

      • Locally advanced or inflammatory disease, or specified subgroup of large operable disease for whom neoadjuvant chemotherapy is appropriate, defined as any 1 of the following:

        • Clinical stage T4a-d, any N (inflammatory breast carcinoma: tumor mass, breast enlargement, oedema and warmth of the skin are often present but not mandatory for the diagnosis)
        • Any clinical T, N2 or N3 (ipsilateral supraclavicular nodes)
        • cT3cN0,1 any estrogen receptor (ER)
        • cT2cN1 any ER
        • cT2cN0 ER negative
      • Presence of bilateral breast cancer is allowed
      • 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)
    • Phase II

      • Locally advanced or inflammatory breast cancer, defined as any 1 of the following:

        • Clinical T4a-d, any N (inflammatory breast carcinoma: tumor mass, breast enlargement, oedema and warmth of the skin are often present but not mandatory for the diagnosis)
        • Any clinical T, N2 or N3 (ipsilateral supraclavicular nodes)
        • And M0
      • Bilateral breast cancer is allowed provided only 1 side is HER2-positive
      • Any large resectable T2 or T3 breast cancers, M0
  • HER2-positive disease by immunohistochemistry, fluorescent in situ hybridization, and/or chromogenic in situ hybridization
  • No CNS involvement
  • Two frozen trucuts for every core biopsy indicated by the translational research study
  • Hormone receptor status:

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


  • 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
  • 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
  • No current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease not requiring therapy as per investigator assessment)
  • No serious cardiac illness or medical condition within the past 6 months including, but not limited to, any of 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
  • Accessible for repeat dosing and follow up
  • No concurrent grapefruit juice
  • 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


  • 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 infusions 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00450892

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C.H.U. Sart-Tilman
Liege, Belgium
Clinique Sainte Elisabeth
Namur, Belgium
Institut Bergonie
Bordeaux, France
Institut Bergonié
Bordeaux, France
CHRU de Limoges
Limoges, France
Centre Leon Berard
Lyon, France
CRLC Val D'Aurelle
Montpellier, France
Centre Henri Becquerel
Rouen, France
Hopital Rene Huguenin - Institut Curie
Saint-Cloud, France
Centre Paul Strauss
Strasbourg, France
Institut Gustave Roussy
Villejuif, France
The Institute Of Oncology
Ljubljana, Slovenia
Hôpitaux universitaires de Genève - HUG - site de Cluse-Roseraie
Geneve, Switzerland
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland
United Kingdom
Western General Hospital
Edinburgh, United Kingdom
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
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Study Chair: David Cameron, MD Edinburgh Cancer Centre at Western General Hospital
Study Chair: Herve Bonnefoi, MD Institut Bergonié
Publications of Results:
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Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00450892    
Other Study ID Numbers: EORTC-10054
2006-000864-94 ( EudraCT Number )
First Posted: March 22, 2007    Key Record Dates
Last Update Posted: July 7, 2016
Last Verified: July 2016
Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
inflammatory breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Protein Kinase Inhibitors
Enzyme Inhibitors