Male Breast Cancer, Recurrent Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer
Conditions
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.
Interventions
DRUGlapatinib ditosylate
Given PO
RADIATIONradiation therapy
Undergo radiation therapy
OTHERlaboratory biomarker analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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 * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
lapatinib ditosylate: Given PO
radiation therapy: Undergo radiation therapy
laboratory biomarker analysis: Correlative studies | 7 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Treatment (Lapatinib Ditosylate, Radiation Therapy) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 7 |
| serious Total, serious adverse events | 3 / 7 |
Outcome results
Primary
Percentage of Patients Achieving Complete Clinical Response
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).
Time frame: Up to 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lapatinib Plus Radiation Therapy | Percentage of Patients Achieving Complete Clinical Response | 2 Participants |
Secondary
Change in the Proportion of BCSCs
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.
Time frame: Baseline to 12 weeks
Population: This outcome was not analyzed due to lack of funding. It may be re-evaluated in the future. Data were not collected and the outcome measure was not analyzed.
Secondary
Feasibility of Assessing the Effects of Lapatinib and Radiation Therapy on BCSCs Using Flow Cytometry and SCGEP
Defined as the percentage of biopsy specimens for which the SCGEP assay achieves a non-zero number.
Time frame: 12 weeks
Population: Data were not collected and the outcome measure was not analyzed.
Secondary
Incidence of Adverse Events Graded According to Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Adverse events will be tabulated by organ system and severity.
Time frame: Up to 12 weeks
Population: Participants enrolled in the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lapatinib Plus Radiation Therapy | Incidence of Adverse Events Graded According to Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Grade 3 Events | 2 incidencts |
| Lapatinib Plus Radiation Therapy | Incidence of Adverse Events Graded According to Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Grade 4 Events | 1 incidencts |
Secondary
Pathologic Complete Response Rate for Those Patients Undergoing Surgical Resection Defined as no Evidence of Residual Tumor in the Breast and Lymph Nodes
Proportion of patients who achieve a pathological complete response will be estimated with 95% exact confidence intervals.
Time frame: Up to 12 weeks
Population: Of the patients in the treatment arm, only 1 received surgery.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lapatinib Plus Radiation Therapy | Pathologic Complete Response Rate for Those Patients Undergoing Surgical Resection Defined as no Evidence of Residual Tumor in the Breast and Lymph Nodes | 0 Participants |