Trial record 1 of 1 for:    NCT01873833
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Capecitabine, Cyclophosphamide, Lapatinib Ditosylate, and Trastuzumab in Treating Patients With HER2-Positive Metastatic Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2015 by University of Southern California
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Southern California Identifier:
First received: June 6, 2013
Last updated: June 8, 2015
Last verified: June 2015
This phase II trial studies how well capecitabine, cyclophosphamide, lapatinib ditosylate, and trastuzumab work in treating patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Drugs used in chemotherapy, such as capecitabine and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving capecitabine and cyclophosphamide daily may kill more tumor cells. Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for growth. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of the tumor to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving capecitabine, cyclophosphamide, lapatinib ditosylate, and trastuzumab together may be an effective treatment for breast cancer.

Condition Intervention Phase
HER2-positive Breast Cancer
Recurrent Breast Cancer
Stage IV Breast Cancer
Drug: capecitabine
Drug: cyclophosphamide
Drug: lapatinib ditosylate
Biological: trastuzumab
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 Trial of Metronomic Capecitabine and Cyclophosphamide With Lapatinib and Trastuzumab in Patients With HER2 Positive Metastatic Breast Cancer Who Have Progressed on a Previous Trastuzumab-Based Regimen

Resource links provided by NLM:

Further study details as provided by University of Southern California:

Primary Outcome Measures:
  • PFS [ 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 ] [ Designated as safety issue: No ]
    One-sided one-sample logrank test will be used to evaluate the improvement in PFS compared to the reported historical PFS rate.

Estimated Enrollment: 40
Study Start Date: July 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (chemotherapy, lapatinib ditosylate, trastuzumab)
Patients receive capecitabine PO QD, cyclophosphamide PO QD, and lapatinib ditosylate PO QD on days 1-21 and trastuzumab IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: capecitabine
Given PO
Other Names:
  • CAPE
  • Ro 09-1978/000
  • Xeloda
Drug: cyclophosphamide
Given PO
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: lapatinib ditosylate
Given PO
Other Names:
  • GSK572016
  • GW-572016
  • GW2016
  • Lapatinib
  • Tykerb
Biological: trastuzumab
Given IV
Other Names:
  • anti-c-erB-2
  • Herceptin
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:


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.


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

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 cancer. In addition, prior Trastuzumab emtansine (TDM-1, Kadcyla) is allowed.
  • 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 used
  • 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 treatment
  • 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 assessment)
  • 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 study
  • Unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee
  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: NCT01873833

United States, California
USC Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Kristy A. Watkins, R.N.    323-865-0452   
Principal Investigator: Agustin A. Garcia         
Sponsors and Collaborators
University of Southern California
National Cancer Institute (NCI)
Principal Investigator: Agustin Garcia University of Southern California
  More Information

No publications provided

Responsible Party: University of Southern California Identifier: NCT01873833     History of Changes
Other Study ID Numbers: 1B-12-10  NCI-2013-01086  P30CA014089 
Study First Received: June 6, 2013
Last Updated: June 8, 2015
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms by Site
Skin Diseases
Alkylating Agents
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses processed this record on February 08, 2016