Clinical trial NCT01868503: Lapatinib Ditosylate and Radiation Therapy in Treating Patients With Locally Advanced or Locally Recurrent Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Male Breast Cancer
Recurrent Breast Cancer
Stage IIIA Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2013-06-04
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Patients Achieving Complete Clinical Response
timeFrame: Up to 12 weeks
Secondary outcomes:
measure: Feasibility of Assessing the Effects of Lapatinib and Radiation Therapy on BCSCs Using Flow Cytometry and SCGEP
timeFrame: 12 weeks
measure: Change in the Proportion of BCSCs
timeFrame: Baseline to 12 weeks
measure: Incidence of Adverse Events Graded According to Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
timeFrame: Up to 12 weeks
measure: Pathologic Complete Response Rate for Those Patients Undergoing Surgical Resection Defined as no Evidence of Residual Tumor in the Breast and Lymph Nodes
timeFrame: Up to 12 weeks
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University Cancer Institute
state: California
Study officials:
affiliation: Stanford University Hospitals and Clinics
name: Kathleen Horst
role: PRINCIPAL_INVESTIGATOR
References: