Phase I/II Study of Neoadjuvant Lapatinib in Breast Cancer

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00450892
First received: March 20, 2007
Last updated: January 20, 2014
Last verified: January 2014
  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: docetaxel+lapatinib
Drug: docetaxel + trastuzumab
Drug: docetaxel + trastuzumab + lapatinib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Phase I part: Dose limiting toxicity during cycle 1 [ Time Frame: during study ] [ Designated as safety issue: Yes ]
  • Phase II: Pathological complete response rate [ Time Frame: end of study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Phase I: Changes in apoptosis and proliferation markers. [ Time Frame: end of Phase I ] [ Designated as safety issue: No ]
  • Phase II: Tolerability, clinical/radiological response rates, breast conserving surgery, pharmacodynamics data [ Time Frame: end of study ] [ Designated as safety issue: No ]

Enrollment: 129
Study Start Date: February 2007
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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


  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 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
  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: NCT00450892

Locations
Belgium
C.H.U. Sart-Tilman
Liege, Belgium
Clinique Sainte Elisabeth
Namur, Belgium
France
Institut Bergonié
Bordeaux, France
Institut Bergonie
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
Slovenia
The Institute Of Oncology
Ljubljana, Slovenia
Switzerland
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
GlaxoSmithKline
Investigators
Study Chair: David Cameron, MD Edinburgh Cancer Centre at Western General Hospital
Study Chair: Herve Bonnefoi, MD Institut Bergonié
  More Information

Additional Information:
Publications:
Cameron DA, Marreaud S, Zaman K, et al.: LAPATAX: A randomized phase II trial of FEC-docetaxel combined with lapatinib and/or trastuzumab as neoadjuvant therapy of HER2-positive breast cancer—EORTC 10054 trial. [Abstract] J Clin Oncol 28 (Suppl 15): A-TPS116, 2010.
Bonnefoi H, Zaman K, Nobahar M, et al.: Lapatax: a phase I study of neoadjuvant lapatinib combined with docetaxel in Her2/neu overexpressing breast cancer (BC) EORTC protocol 10054. [Abstract] 31st Annual San Antonio Breast Cancer Symposium, December 10-14, 2008, San Antonio, Texas. A-5112, 2008.

Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00450892     History of Changes
Other Study ID Numbers: EORTC-10054, EORTC-10054, GSK-EORTC-10054, 2006-000864-94
Study First Received: March 20, 2007
Last Updated: January 20, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
United Kingdom: Medicines and Healthcare Products Regulatory Agency

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:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Docetaxel
Trastuzumab
Lapatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014