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

NCT ID: NCT01873833

Last Updated: 2023-10-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-29
• Study Completion Date: 2021-03-02

Brief Summary

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (chemotherapy, lapatinib ditosylate, trastuzumab)

Patients receive capecitabine by mouth (PO) every day (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.

Group Type: EXPERIMENTAL

capecitabine

Intervention Type: DRUG

Given PO

cyclophosphamide

Intervention Type: DRUG

Given PO

lapatinib ditosylate

Intervention Type: DRUG

Given PO

trastuzumab

Intervention Type: BIOLOGICAL

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

capecitabine

Given PO

Intervention Type: DRUG

cyclophosphamide

Given PO

Intervention Type: DRUG

lapatinib ditosylate

Given PO

Intervention Type: DRUG

trastuzumab

Given IV

Intervention Type: BIOLOGICAL

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

CAPE; Ro 09-1978/000; Xeloda; CPM; CTX; Cytoxan; Endoxan; Endoxana; GSK572016; GW-572016; GW2016; Lapatinib; Tykerb; anti-c-erB-2; Herceptin; Monoclonal antibody (MOAB) HER2; MOAB HER2

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: chromosome enumeration probe (CEP)17 > 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Southern California

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Darcy V Spicer, MD

Role: PRINCIPAL_INVESTIGATOR

University of Southern California

Locations

USC Norris Comprehensive Cancer Center

Los Angeles, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2013-01086

Identifier Type: REGISTRY

Identifier Source: secondary_id

P30CA014089

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1B-12-10

Identifier Type: -

Identifier Source: org_study_id