Status:

COMPLETED

Phase I/II Study of Neoadjuvant Lapatinib in Breast Cancer

Lead Sponsor:

European Organisation for Research and Treatment of Cancer - EORTC

Collaborating Sponsors:

GlaxoSmithKline

Conditions:

Breast Cancer

Eligibility:

FEMALE

18-70 years

Phase:

PHASE1

PHASE2

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 st...

Detailed Description

OBJECTIVES: Primary * Determine the maximum tolerated dose of neoadjuvant therapy comprising docetaxel and lapatinib ditosylate before or after fluorouracil, epirubicin hydrochloride, and cyclophosp...

Eligibility Criteria

Inclusion

  • DISEASE CHARACTERISTICS:
  • 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
  • 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
  • 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
  • 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 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

Exclusion

    Key Trial Info

    Start Date :

    February 1 2007

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ACTUAL

    End Date :

    July 1 2013

    Estimated Enrollment :

    129 Patients enrolled

    Trial Details

    Trial ID

    NCT00450892

    Start Date

    February 1 2007

    End Date

    July 1 2013

    Last Update

    July 7 2016

    Active Locations (15)

    Enter a location and click search to find clinical trials sorted by distance.

    Page 1 of 4 (15 locations)

    1

    C.H.U. Sart-Tilman

    Liège, Belgium

    2

    Clinique Sainte Elisabeth

    Namur, Belgium

    3

    Institut Bergonie

    Bordeaux, France

    4

    Institut Bergonié

    Bordeaux, France

    Phase I/II Study of Neoadjuvant Lapatinib in Breast Cancer | DecenTrialz