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

Unicancer

Status and phase

Completed

Phase 2

Conditions

Metastatic Cancer

Breast Cancer

Treatments

Other: circulating tumor cell analysis

Other: laboratory biomarker analysis

Drug: capecitabine

Drug: lapatinib ditosylate

Study type

Interventional

Funder types

Other

Identifiers

NCT00967031

EU-20940

2008-001084-10 (EudraCT Number)

CDR0000642631

GEP 02-0801

Details and patient eligibility

About

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.

Full description

OBJECTIVES:

Primary

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.

Secondary

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.

Tertiary

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.

Enrollment

45 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

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

PRIOR CONCURRENT THERAPY:

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)