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

NCT00967031 | Completed Phase 2

• 4 other identifiers: CDR0000642631EU-20940GEP 02-08012008-001084-10
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer; Metastatic Cancer

Keywords

HER2-positive breast cancer; male breast cancer; stage IV breast cancer; tumors metastatic to brain

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  february 2012

Secondary Outcomes (7)

• Toxicity as assessed by NCI CTC v3.0

  february 2012

• Time to radiotherapy

  february 2012

• Time to disease progression

  february 2012

• Overall response rate

  february 2012

• Clinical benefit (complete response, partial response, and stable disease for at least 6 months)

  february 2012

Study Arms (1)

Lapatinib + capecitabine

EXPERIMENTAL

lapatinib 1250mg/day + capecitabine 2000mg/m2/day

Drug: capecitabine; Drug: lapatinib ditosylate; Other: circulating tumor cell analysis; Other: laboratory biomarker analysis

Interventions

capecitabine DRUG

Lapatinib + capecitabine

lapatinib ditosylate DRUG

Lapatinib + capecitabine

circulating tumor cell analysis OTHER

Lapatinib + capecitabine

laboratory biomarker analysis OTHER

Lapatinib + capecitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• UNICANCER: lead

Study Sites (1)

Centre Leon Berard

Lyon, 69373, France

Location

Related Publications (2)

• Pierga JY, Bidard FC, Cropet C, Tresca P, Dalenc F, Romieu G, Campone M, Mahier Ait-Oukhatar C, Le Rhun E, Goncalves A, Leheurteur M, Domont J, Gutierrez M, Cure H, Ferrero JM, Labbe-Devilliers C, Bachelot T. Circulating tumor cells and brain metastasis outcome in patients with HER2-positive breast cancer: the LANDSCAPE trial. Ann Oncol. 2013 Dec;24(12):2999-3004. doi: 10.1093/annonc/mdt348. Epub 2013 Sep 6.

  PMID: 24013510 DERIVED

• Bachelot T, Romieu G, Campone M, Dieras V, Cropet C, Dalenc F, Jimenez M, Le Rhun E, Pierga JY, Goncalves A, Leheurteur M, Domont J, Gutierrez M, Cure H, Ferrero JM, Labbe-Devilliers C. Lapatinib plus capecitabine in patients with previously untreated brain metastases from HER2-positive metastatic breast cancer (LANDSCAPE): a single-group phase 2 study. Lancet Oncol. 2013 Jan;14(1):64-71. doi: 10.1016/S1470-2045(12)70432-1. Epub 2012 Nov 2.

  PMID: 23122784 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis; Breast Neoplasms, Male; Brain Neoplasms

Interventions

Capecitabine; Lapatinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Thomas Bachelot, MD

  Centre Leon Berard

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2009
• First Posted: August 27, 2009
• Study Start: April 1, 2009
• Primary Completion: February 1, 2012
• Last Updated: January 18, 2013

Record last verified: 2013-01

Locations

FR (1)