Know Cancer

forgot password

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

Phase 2
18 Years
Not Enrolling
Breast Cancer, Metastatic Cancer

Thank you

Trial Information

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



- 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.

Inclusion Criteria


- 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

- 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)

Type of Study:


Study Design:

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

Outcome Measure:

Objective response rate

Outcome Time Frame:

february 2012

Safety Issue:


Principal Investigator

Thomas Bachelot, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Centre Leon Berard


AFSSAPS : agence française de sécurité Sanitaire des produits de santé

Study ID:




Start Date:

April 2009

Completion Date:

Related Keywords:

  • Breast Cancer
  • Metastatic Cancer
  • HER2-positive breast cancer
  • male breast cancer
  • stage IV breast cancer
  • tumors metastatic to brain
  • Breast Neoplasms
  • Neoplasm Metastasis
  • Neoplasms
  • Neoplasms, Second Primary