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Lapatinib and Radiation Therapy in Treating Patients With Locally Recurrent or Chemotherapy-Refractory Locally Advanced or Metastatic Breast Cancer

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ClinicalTrials.gov Identifier: NCT00379509
Recruitment Status : Completed
First Posted : September 22, 2006
Last Update Posted : March 21, 2017
Information provided by (Responsible Party):

Study Description
Brief Summary:

RATIONALE: Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving lapatinib together with radiation therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of lapatinib when given together with radiation therapy in treating patients with locally recurrent or chemotherapy-refractory locally advanced or metastatic breast cancer.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: lapatinib ditosylate Genetic: TdT-mediated dUTP nick end labeling assay Genetic: gene expression analysis Genetic: microarray analysis Other: immunohistochemistry staining method Procedure: biopsy Radiation: radiation therapy Phase 1

Detailed Description:



  • Determine the toxicity of lapatinib ditosylate and radiotherapy in patients with locally recurrent breast cancer or chemotherapy-refractory, locally advanced or metastatic breast cancer.
  • Determine the impact of this drug on inhibition of receptor and downstream signal transduction pathway activation in tumor tissue, in the context of inhibitor dose escalation with or without radiotherapy.


  • Determine, preliminarily, the efficacy of lapatinib ditosylate and radiotherapy in these patients.
  • Correlate response in these patients with inhibition of downstream signaling.
  • Assess gene expression changes in tumor biopsy samples from patients treated with lapatinib ditosylate alone or in combination with radiotherapy.

OUTLINE: This is a multicenter, parallel group, dose-escalation study of lapatinib ditosylate. Patients are stratified according to prior radiotherapy (yes vs no).

  • Group I (prior radiotherapy): Patients receive oral lapatinib ditosylate once daily in the absence of disease progression or unacceptable toxicity. Beginning on day 8 of lapatinib ditosylate therapy, patients undergo concurrent radiotherapy 5 days a week for up to 5 weeks.
  • Group II (no prior radiotherapy): Patients receive oral lapatinib ditosylate as in group I. Beginning on day 8, patients undergo concurrent radiotherapy 5 days a week for up to 7 weeks.

In each group, cohorts of 3-6 patients receive escalating doses of lapatinib ditosylate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity during the first course.

Patients undergo skin punch or core biopsy at baseline* and on day 8 and day 15. Tumor biopsy samples are examined by IHC for evaluation of EGFR, phospho-EGFR, HER2, phospho-HER2, phospho-Akt, and phospho-MAPK. Samples are also examined for cell proliferation by Ki-67, apoptosis by TUNEL, and angiogenesis by microvessel density. Additionally, mRNA is extracted from fresh frozen samples and examined by microarray analysis.

NOTE: *Archival tissue acceptable for baseline sample, if available

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Radiosensitization Study of GW572016 With Biologic Correlates in Locoregionally Recurrent Breast Cancer
Study Start Date : April 2006
Primary Completion Date : June 2010
Study Completion Date : August 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: GW572016 Drug: lapatinib ditosylate
Patients will be assigned in cohorts of 3. Dose levels of GW572106 will include 500mg, 1000mg,1500 mg (additional levels at 750 mg and 1250 mg will be added if needed). Lapatinib is an oral drug. It is taken every day.
Genetic: TdT-mediated dUTP nick end labeling assay
Genetic analysis of tumor tissue
Genetic: gene expression analysis
Genetic analysis of tumor tissue.
Genetic: microarray analysis
Genetic analysis of tumor tissue.
Other: immunohistochemistry staining method
Laboratory analysis of tumor tissue.
Procedure: biopsy
Serial biopsies by skin punch or core biopsy or fine needle aspiration.
Radiation: radiation therapy
Radiotherapy will be delivered at standard dose and fractionation. For patients who have not received previous locoregional radiotherapy, 50-56 Gy will be delivered to the regional lymph nodes and/or chest wall at a dose of 2 Gy per fraction, 5 days per week followed by a boost to the sites of gross involvement to a total dose of 60-70 Gy over a course of 6-7 weeks. For patients who have received adjuvant radiotherapy, a dose of 35-45 Gy will be delivered to sites of chest wall involvement at a dose of 1.8 Gy per fraction over 4-5 weeks. In either de novo or reirradiated settings, the total dose to the brachial plexus will not exceed 60 Gy.

Outcome Measures

Primary Outcome Measures :
  1. Toxicity as assessed by NCI CTCAE v3.0 [ Time Frame: 4-5 years ]
  2. Inhibition of receptor and downstream signal transduction pathway activation in tumor tissue as assessed by IHC [ Time Frame: 4-5 years ]

Secondary Outcome Measures :
  1. Efficacy [ Time Frame: 4-5 years ]
  2. Correlation of response with inhibition of downstream signaling [ Time Frame: 4-5 years ]
  3. Gene expression [ Time Frame: 4-5 years ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Diagnosis of breast cancer meeting 1 of the following criteria:

    • Locally recurrent disease
    • Locally advanced disease AND meets the following criterion:

      • Chemotherapy-refractory disease (achieved < partial response to ≥ 3 courses of neoadjuvant chemotherapy)
    • Metastatic disease
  • Evaluable disease by exam and/or imaging studies

    • Amenable to serial biopsies by skin punch, core biopsy, or fine-needle aspiration
  • Unresectable disease after standard neoadjuvant chemotherapy

    • Resectability must be determined by a surgical oncologist prior to treatment
  • Stable CNS metastases allowed
  • Hormone receptor status not specified


  • Male or female
  • Menopausal status not specified
  • Life expectancy > 12 weeks
  • ECOG performance status 0-2
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Able to swallow and retain oral medication
  • WBC ≥ 3,000/mm³
  • ANC ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Total bilirubin normal
  • AST and ALT ≤ 2.5 times upper limit of normal
  • Creatinine normal OR creatinine clearance ≥ 60 mL/min
  • Cardiac ejection fraction normal by ECHO or MUGA
  • No other malignancy within the past 5 years
  • No concurrent disease or condition that would preclude study participation
  • No ongoing coagulopathy
  • No active severe infection


  • See Disease Characteristics
  • Recovered from prior therapy
  • At least 3 weeks since prior and no other concurrent systemic therapy for breast cancer
  • At least 14 days since prior and no concurrent herbal or alternative medicine
  • At least 14 days since prior and no concurrent dietary supplement
  • At least 14 days since prior CYP3A4 inducers
  • At least 7 days since prior CYP3A4 inhibitors
  • No antacid within 1 hour before or after study drug administration
  • Concurrent bisphosphonate allowed
  • No concurrent oral glucocorticosteroid > 1.5 mg of dexamethasone (or equivalent)
Contacts and Locations

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): NCT00379509

United States, North Carolina
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7295
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Elizabeth C. Dees, MD UNC Lineberger Comprehensive Cancer Center
More Information

Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00379509     History of Changes
Other Study ID Numbers: LCCC 0411
P30CA016086 ( U.S. NIH Grant/Contract )
First Posted: September 22, 2006    Key Record Dates
Last Update Posted: March 21, 2017
Last Verified: March 2017

Keywords provided by UNC Lineberger Comprehensive Cancer Center:
recurrent breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer
male breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action