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Phase II Trial of Metronomic Capecitabine and Cyclophosphamide With Lapatinib and Ttrastuzumab in Patients With HER2 Positive Metastatic Breast Cancer Who Have Progressed on a Previous Trastuzumab-Based Regimen

Phase 2
18 Years
Not Enrolling
HER2-positive Breast Cancer, Recurrent Breast Cancer, Stage IV Breast Cancer

Thank you

Trial Information

Phase II Trial of Metronomic Capecitabine and Cyclophosphamide With Lapatinib and Ttrastuzumab in Patients With HER2 Positive Metastatic Breast Cancer Who Have Progressed on a Previous Trastuzumab-Based Regimen


I. To estimate the progression free survival (PFS).


I. To evaluate the overall response rate (ORR).

II. To evaluate the clinical benefit rate (CBR; complete response, partial response, and
stable disease for >= 24 weeks).

III. To estimate the overall survival (OS).

IV. To assess the safety and tolerability.


Patients receive capecitabine orally (PO) once daily (QD), cyclophosphamide PO QD, and
lapatinib ditosylate PO QD on days 1-21 and trastuzumab intravenously (IV) on day 1. Courses
repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year.

Inclusion Criteria:

- Histologically confirmed HER2-positive metastatic breast cancer

- HER2 overexpression of tumor by either immunohistochemistry (IHC) or fluorescence in
situ hybridization (FISH); tumors tested by IHC must be 3+ positive; tumors tested by
FISH must have a ratio of HER2:CEP17 > 2.0; when both tests are performed, the FISH
result must be positive

- Prior trastuzumab use in the adjuvant or metastatic setting

- No more than two prior cytotoxic chemotherapeutic regimens for metastatic breast

- Eastern Cooperative Oncology Group (ECOG) performance status of =< 2

- Absolute neutrophil count (ANC) >= 1500/mm^3

- Platelets >= 100,000/mm^3

- Hemoglobin >= 9 g/dL

- Bilirubin =< 1.5 x upper limit of normal (ULN)

- Serum creatinine =< 1.5 x ULN or calculated creatinine clearance >= 60 ml/min

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN

- Fully recovered from toxicity due to prior therapy

- Capable of understanding the informed consent and complying with the protocol and
signed the informed consent document prior to any study-specific screening procedures
or evaluations being performed

- Must be able to swallow pills

- May have either measurable or non-measurable disease by Response Evaluation Criteria
in Solid Tumors (RECIST) 1.1 criteria

- Sexually active participants must agree to use a medically accepted barrier method of
contraception (i.e. male condom or female condom) during the course of the study and
for 3 months following discontinuation of study treatments; for participants of
childbearing potential, a barrier method and a second method of contraception must be

- Participants of childbearing potential must have a negative pregnancy test at
screening and enrollment; participants of childbearing potential are defined as
premenopausal females capable of becoming pregnant, i.e. females who have had any
evidence of menses in the past 12 months with the exception of those who had prior
hysterectomy (oophorectomy or surgical sterilization); however, women who have been
amenorrheic for >= 12 months are still considered to be of childbearing potential if
the amenorrhea is possibly due to any other cause including prior chemotherapy,
antiestrogens, or ovarian suppression

Exclusion Criteria:

- Prior treatment with capecitabine or lapatinib

- Radiation therapy within 2 weeks before the first dose of study treatment

- Hormonal therapy within 2 weeks before the first dose of study treatment

- Cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) within 3
weeks before the first dose of study treatment

- Biologic therapy (including antibodies [other than trastuzumab], immune modulators,
cytokines) within 4 weeks before the first dose of study treatment; Note: there is no
washout period required for trastuzumab

- Any other type of investigational agent within 4 weeks before the first dose of study

- Major surgery, or not recovered from major surgery within 4 weeks before the first
dose of study treatment

- Untreated, symptomatic, or progressive brain metastases; participants must have no
radiographic or other signs of progression in the brain for >= 1 month after
completion of local therapy; any corticosteroid use for brain metastases must have
been discontinued without the subsequent appearance of symptoms for >= 4 weeks prior
to first study treatment

- Uncontrolled significant intercurrent illness that would preclude the patient from
study participation per investigator assessment

- Left ventricular ejection fraction (LVEF) =< 50% as documented by multi gated
acquisition scan (MUGA) or echocardiogram performed within 28 days prior to the first
study treatment

- Currently receiving anticoagulation with therapeutic doses of warfarin (low-molecular
weight heparin is permitted)

- Pregnant or breastfeeding

- Known to be positive for the human immunodeficiency virus (HIV) (a test for HIV at
screening is not required)

- Have acute or currently active/requiring anti-viral therapy hepatic or biliary
disease (with the exception of patients with Gilbert's syndrome, asymptomatic
gallstones, liver metastases or stable chronic liver disease per investigator

- Previously identified allergy or hypersensitivity or intolerance to components of the
study treatment formulation (cyclophosphamide, capecitabine, lapatinib [lapatinib
ditosylate], trastuzumab)

- Any other diagnosis of malignancy or evidence of malignancy (except non-melanoma skin
cancer, in-situ carcinoma of the cervix) within 2 years prior to screening for this

- Unable or unwilling to abide by the study protocol or cooperate fully with the
investigator or designee

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:


Outcome Description:

One-sided one-sample logrank test will be used to evaluate the improvement in PFS compared to the reported historical PFS rate.

Outcome Time Frame:

From the date of registration to date of first documentation of progression or symptomatic deterioration or death due to any cause, assessed up to 1 year

Safety Issue:


Principal Investigator

Agustin Garcia

Investigator Role:

Principal Investigator

Investigator Affiliation:

USC/Norris Comprehensive Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

July 2013

Completion Date:

July 2016

Related Keywords:

  • HER2-positive Breast Cancer
  • Recurrent Breast Cancer
  • Stage IV Breast Cancer
  • Breast Neoplasms



USC Norris Comprehensive Cancer Center Los Angeles, California  90089