Lapatinib Ditosylate and Radiation Therapy in Treating Patients With Locally Advanced or Locally Recurrent Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Stanford University
Information provided by (Responsible Party):
Stanford University Identifier:
First received: May 30, 2013
Last updated: July 31, 2014
Last verified: July 2014

This phase II trial studies how well lapatinib ditosylate and radiation therapy work in treating patients with locally advanced or locally recurrent breast cancer. Lapatinib ditosylate 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 ditosylate together with radiation therapy may be an effective treatment for breast cancer.

Condition Intervention Phase
Male Breast Cancer
Recurrent Breast Cancer
Stage IIIA Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Drug: lapatinib ditosylate
Radiation: radiation therapy
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study to Investigate Concurrent Lapatinib and Radiotherapy in Locally Advanced or Locally Recurrent Breast Cancer and the Impact on Breast Cancer Stem Cells

Resource links provided by NLM:

Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Percentage of patients achieving complete clinical response [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
    Complete clinical response will be defined as the absence of tumor on the chest wall, in the treated breast, or in the nodal regions as assessed by clinical examination +/- radiographic imaging (if clinically indicated).

Secondary Outcome Measures:
  • Feasibility of assessing the effects of lapatinib and radiation therapy on BCSCs using flow cytometry and SCGEP [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Defined as the percentage of biopsy specimens for which the SCGEP assay achieves a non-zero number.

  • Change in the proportion of BCSCs [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Defined as the difference between the percentage of BCSCs before and after treatment. Proportion of biopsy samples that are evaluable for BCSCs will be estimated along with 95% exact confidence intervals. BCSC results will be summarized using medians and interquartile ranges. Changes in BCSCs will be assessed using the Wilcoxon signed rank test.

  • Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: Yes ]
    Adverse events will be tabulated by organ system and severity.

  • Pathologic complete response rate for those patients undergoing surgical resection defined as no evidence of residual tumor in the breast and lymph nodes [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
    Proportion of patients who achieve a pathological complete response will be estimated with 95% exact confidence intervals.

Estimated Enrollment: 22
Study Start Date: July 2013
Estimated Primary Completion Date: January 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (lapatinib ditosylate, radiation therapy)
Patients receive lapatinib ditosylate PO QD on day 1 until completion of radiation therapy. Beginning on day 7, patients undergo radiation therapy for 5-7 weeks.
Drug: lapatinib ditosylate
Given PO
Other Names:
  • GSK572016
  • GW-572016
  • GW2016
  • Lapatinib
  • Tykerb
Radiation: radiation therapy
Undergo radiation therapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:


I. To assess the clinical complete response rate (CR) after concurrent lapatinib (lapatinib ditosylate) and radiotherapy in patients with locally advanced or locally recurrent breast cancer that is refractory to chemotherapy.


I. To evaluate the feasibility of assessing breast cancer stem cells (BCSCs) using flow cytometry and single cell gene expression profiling (SCGEP).

II. To determine the change in the proportion of BCSCs after combined modality therapy.

III. To evaluate the safety and efficacy of the combination of lapatinib and radiotherapy.

IV. To assess the pathologic complete response rate (pCR) in those undergoing surgical resection.


Patients receive lapatinib ditosylate orally (PO) once daily (QD) on day 1 until completion of radiation therapy. Beginning on day 7, patients undergo radiation therapy for 5-7 weeks.

After completion of study treatment, patients are followed up at 2-4 weeks and then at 6-12 weeks.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients with histologically or cytologically confirmed locally advanced breast cancer that is refractory to chemotherapy or other therapeutic agents or with a history of breast cancer with new evidence of a local recurrence (defined as a chest wall or breast recurrence and/or nodal recurrence); the diagnosis will be made based on clinical and pathologic features
  • Prior radiotherapy and/or chemotherapy is allowed
  • Life expectancy must be greater than 3 months
  • Karnofsky performance status (KPS) score >= 70
  • Total bilirubin =< 1.5 x institutional upper limit of normal
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
  • Alkaline phosphatase =< 2.5 x institutional upper limit of normal
  • Creatinine =< 1.5 x institutional upper limit of normal
  • Patients must have left-ventricular ejection fraction > 50% at baseline
  • Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients who have contraindications to radiotherapy, such as scleroderma, dermatomyositis, or severe cutaneous manifestations of systemic lupus erythematosus (SLE)
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, or psychiatric illness/social situations that would limit compliance with study requirements
  • Women who are pregnant or lactating, as well as women of child-bearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the duration of the study
  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 identifier: NCT01868503

United States, California
Stanford University Cancer Institute Recruiting
Stanford, California, United States, 94305
Contact: Amanda Simmons    650-724-4606   
Principal Investigator: Kathleen C. Horst         
Sponsors and Collaborators
Stanford University
Principal Investigator: Kathleen Horst Stanford University Hospitals and Clinics
  More Information

No publications provided

Responsible Party: Stanford University Identifier: NCT01868503     History of Changes
Other Study ID Numbers: BRS0027, NCI-2013-01065, P30CA124435
Study First Received: May 30, 2013
Last Updated: July 31, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms by Site
Skin Diseases
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses processed this record on March 26, 2015