Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Objectives

Primary

1. 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

1. To document any toxicity evaluated by NCI CTC v3.0.
2. To assess the time to radiotherapy.
3. To document the time to disease progression in the central nervous system (CNS) of these patients.
4. To evaluate the overall response rate for extra-CNS disease.
5. 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

1. To evaluate serum proteomic and metabonomic markers as predictors of response.
2. To evaluate the predictive value of circulating tumor cells (CTC) on response.

Entry 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

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 isoenzyme 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)

Patient Characteristics:

• Menopausal status not specified
• ECOG performance status 0-2
• Life expectancy ≥ 3 months
• ANC ≥ 1,000/mm³
• Platelet count ≥ 100,000/mm³
• 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)
• AST and ALT ≤ 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, 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 DLCO ≤ 50% of normal, and O₂ 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

Expected Enrollment

Outcomes

Objective response rate

Toxicity as assessed by NCI CTC v3.0
Time to radiotherapy
Time to disease progression
Overall response rate
Clinical benefit (complete response, partial response, and stable disease for at least 6 months)
Evaluation of serum proteomic and metabonomic markers as predictors of response
Evaluation of the predictive value of circulating tumor cells 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.

Trial Contact Information

Trial Lead Organizations

Federation Nationale des Centres de Lutte Contre le Cancer

Thomas Bachelot, MD, Principal investigator		Ph: 33-4-78-78-26-54 Email: bachelot@lyon.fnclcc.fr

France
	Lyon
	Centre Leon Berard
		Thomas Bachelot, MD	Ph:  33-4-78-78-26-54
			Email: bachelot@lyon.fnclcc.fr

Registry Information
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
Trial Start Date		2009-04-15
Registered in ClinicalTrials.gov		NCT00967031
Date Submitted to PDQ		2009-05-07
Information Last Verified		2011-08-22

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