Working… Menu

Lapatinib Ditosylate and Capecitabine in Treating Patients With Stage IV Breast Cancer and Brain Metastases

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00967031
Recruitment Status : Completed
First Posted : August 27, 2009
Last Update Posted : January 18, 2013
Information provided by (Responsible Party):

Brief Summary:

RATIONALE: Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving lapatinib ditosylate together with capecitabine may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving lapatinib ditosylate together with capecitabine works in treating patients with stage IV breast cancer and brain metastases.

Condition or disease Intervention/treatment Phase
Breast Cancer Metastatic Cancer Drug: capecitabine Drug: lapatinib ditosylate Other: circulating tumor cell analysis Other: laboratory biomarker analysis Phase 2

Detailed Description:



  • To assess the objective response rate by volumetric analysis of brain metastasis as assessed by MRI in patients with HER2-positive stage IV breast cancer treated with lapatinib ditosylate and capecitabine.


  • To document any toxicity evaluated by NCI CTC v3.0.
  • To assess the time to radiotherapy.
  • To document the time to disease progression in the central nervous system (CNS) of these patients.
  • To evaluate the overall response rate for extra-CNS disease.
  • To assess the clinical benefit (complete response, partial response, and stable disease for ≥ 6 months) for both CNS and extra-CNS disease in these patients.


  • To evaluate serum proteomics and metabonomics markers as predictors of response.
  • To evaluate the predictive value of circulating tumor cells (CTC) on response.

OUTLINE: This is a multicenter study.

Patients receive oral lapatinib ditosylate once daily. Patients also receive oral capecitabine twice daily on days 1-14. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 45 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter Phase II Clinical Trial Assessing the Efficacy of the Combination of Lapatinib and Capecitabine in Patients With Non Pretreated Brain Metastasis From HER2 Positive Breast Cancer
Study Start Date : April 2009
Actual Primary Completion Date : February 2012

Arm Intervention/treatment
Experimental: Lapatinib + capecitabine
lapatinib 1250mg/day + capecitabine 2000mg/m2/day
Drug: capecitabine
Drug: lapatinib ditosylate
Other: circulating tumor cell analysis
Other: laboratory biomarker analysis

Primary Outcome Measures :
  1. Objective response rate [ Time Frame: february 2012 ]

Secondary Outcome Measures :
  1. Toxicity as assessed by NCI CTC v3.0 [ Time Frame: february 2012 ]
  2. Time to radiotherapy [ Time Frame: february 2012 ]
  3. Time to disease progression [ Time Frame: february 2012 ]
  4. Overall response rate [ Time Frame: february 2012 ]
  5. Clinical benefit (complete response, partial response, and stable disease for at least 6 months) [ Time Frame: february 2012 ]
  6. Evaluation of serum proteomics and metabonomics markers as predictors of response [ Time Frame: may 2012 ]
  7. Evaluation of the predictive value of circulating tumor cells on response [ Time Frame: february 2012 ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed invasive breast cancer

    • Stage IV disease
  • At least 1 measurable CNS lesion ≥ 10 mm on T1-weighted gadolinium-enhanced MRI

    • No single brain metastasis that could be treated by surgery
  • HER-2 positive primary tumor as defined as IHC3+ or IHC2+ and FISH-positive
  • Hormone receptor status: not specified


  • Menopausal status not specified
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Life expectancy ≥ 3 months
  • Absolute Neutrophil Count (ANC) ≥ 1,000/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 10g/dL
  • Creatinine ≥ 1.5 times upper limit of normal (ULN)
  • Albumin ≥ 2.5 g/dL
  • Serum bilirubin ≤ 1.5 times ULN (unless due to Gilbert's syndrome)
  • ASAT and ALAT ≤ 3 times ULN (≤ 5 times ULN with documented liver metastasis)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception 2 weeks before, during, and for 28 days after completion of study treatment (female) or for 1 week after completion of treatment (male)
  • Able to swallow and retain oral medication
  • Affiliated to a Social Security System
  • No known contraindication to MRI
  • No prior or active malignancy, unless disease free for ≥ 10 years
  • No other concurrent severe and/or uncontrolled medical disease which could compromise study participation, including any of the following:

    • Infection
    • Cardiac disease (e.g., uncontrolled hypertension, congestive cardiac failure, ventricular arrhythmias, active ischemic heart disease, myocardial infarction within the past year, Left Ventricular EJection Fraction (LVEF) > grade 2)
    • Current active hepatic or biliary disease (except for Gilbert syndrome, asymptomatic gallstones, liver metastasis or stable chronic liver disease per investigator assessment)
    • Renal disease
    • Active gastrointestinal (GI) tract ulceration, malabsorption syndrome, active uncontrolled ulcerative colitis, or disease significantly affecting GI function
    • Severely impaired lung function (e.g., spirometry and diffusion capacity of lung for carbon monoxide (DLCO) ≤ 50% of normal, and O_2 saturation ≤ 88% at rest on room air)
  • No known dihydropyrimidine dehydrogenase deficiency
  • No significantly altered mental status prohibiting the understanding of the study, or with psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
  • Not deprived of liberty or placed under the authority of a tutor


  • At least 2 weeks since prior breast cancer treatment (e.g., trastuzumab, chemotherapy, immunotherapy or biological response modifiers, endocrine therapy, or radiotherapy)
  • More than 30 days since prior investigational drugs
  • More than 14 days since prior and no concurrent strong inhibitors or inducers of the cytochrome P450 isoenzyme 3A4 (CYP3A4) (i.e., clarithromycin, ketoconazole, itraconazole, voriconazole, ritonavir)
  • No prior whole brain radiotherapy (WBRT) or brain stereotactic radiotherapy
  • No prior treatment with capecitabine and/or lapatinib ditosylate
  • No prior resection of the stomach or small bowel
  • No concurrent systemic treatment or radiation therapy for breast cancer (except corticosteroid, bisphosphonates, or mannitol)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00967031

Layout table for location information
Centre Leon Berard
Lyon, France, 69373
Sponsors and Collaborators
Layout table for investigator information
Principal Investigator: Thomas Bachelot, MD Centre Leon Berard

Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information
Responsible Party: UNICANCER Identifier: NCT00967031     History of Changes
Other Study ID Numbers: CDR0000642631
GEP 02-0801
2008-001084-10 ( EudraCT Number )
First Posted: August 27, 2009    Key Record Dates
Last Update Posted: January 18, 2013
Last Verified: January 2013
Keywords provided by UNICANCER:
HER2-positive breast cancer
male breast cancer
stage IV breast cancer
tumors metastatic to brain
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors