Clinical Trials /

Capecitabine, Cyclophosphamide, Lapatinib Ditosylate, and Trastuzumab in Treating Patients With HER2-Positive Metastatic Breast Cancer

NCT01873833

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Capecitabine, Cyclophosphamide, Lapatinib Ditosylate, and Trastuzumab in Treating Patients With HER2-Positive Metastatic Breast Cancer
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 1B-12-10
  • SECONDARY ID: NCI-2013-01086
  • SECONDARY ID: P30CA014089
  • NCT ID: NCT01873833

Conditions

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

Interventions

DrugSynonymsArms
capecitabineCAPE, Ro 09-1978/000, XelodaTreatment (chemotherapy, lapatinib ditosylate, trastuzumab)
cyclophosphamideCPM, CTX, Cytoxan, Endoxan, EndoxanaTreatment (chemotherapy, lapatinib ditosylate, trastuzumab)
lapatinib ditosylateGSK572016, GW-572016, GW2016, Lapatinib, TykerbTreatment (chemotherapy, lapatinib ditosylate, trastuzumab)
trastuzumabanti-c-erB-2, Herceptin, MOAB HER2Treatment (chemotherapy, lapatinib ditosylate, trastuzumab)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVES:

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

      SECONDARY OBJECTIVES:

      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.

      OUTLINE:

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (chemotherapy, lapatinib ditosylate, trastuzumab)ExperimentalPatients 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.
  • capecitabine
  • cyclophosphamide
  • lapatinib ditosylate
  • trastuzumab

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:University of Southern California

Last Updated

August 26, 2021