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

Phase 2

Terminated

Conditions: Male Breast Cancer
Recurrent Breast Cancer
Stage IIIA Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer

Interventions: Drug: lapatinib ditosylate
Radiation: radiation therapy
Other: laboratory biomarker analysis

Brief Summary: 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.

Detailed Description: PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

OUTLINE:

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.

Recruitment & Eligibility

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
Patients must be >18 years of age.
Karnofsky Performance Status (KPS) score > 70
Patts must have normal organ function as defined below:
- total bilirubin < 1.5 x institutional upper limit of normal
- AST(SGOT)/ALT(SGPT) < 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.

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

Arm && Interventions

Group	Intervention	Description
Lapatinib Plus Radiation Therapy	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 and will have their blood banked for laboratory biomarker analysis.
Lapatinib Plus Radiation Therapy	lapatinib ditosylate	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 and will have their blood banked for laboratory biomarker analysis.
Lapatinib Plus Radiation Therapy	laboratory biomarker analysis	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 and will have their blood banked for laboratory biomarker analysis.

Primary Outcome Measures

Name	Time	Method
Percentage of Patients Achieving Complete Clinical Response	Up to 12 weeks	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

Name	Time	Method
Feasibility of Assessing the Effects of Lapatinib and Radiation Therapy on BCSCs Using Flow Cytometry and SCGEP	12 weeks	Defined as the percentage of biopsy specimens for which the SCGEP assay achieves a non-zero number.
Change in the Proportion of BCSCs	Baseline to 12 weeks	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	Up to 12 weeks	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	Up to 12 weeks	Proportion of patients who achieve a pathological complete response will be estimated with 95% exact confidence intervals.

Locations (1): Stanford University Cancer Institute
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Stanford, California, United States