A Phase II Study of Lapatinib for Brain Metastases in Subjects with ErbB2-Positive Breast Cancer Following Trastuzumab-based Systemic Therapy and Cranial Radiotherapy - NON APPLICABILE

Phase 1

• Conditions: Brain Metastases in Subjects with ErbB2-Positive Breast Cancer; MedDRA version: 14.1Level: PTClassification code 10061287Term: Metastases to nervous systemSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2005-003944-68-IT
• Lead Sponsor: GLAXO SMITH KLINE RESEARCH & DEVELOPMENT LTD

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-08-30
• Last Update Posted: 19 February 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

? Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2; ? Subjects must have histologically or cytologically confirmed invasive breast cancer, with Stage IV disease; ? ErbB2 overexpressing breast cancer, defined as 3+ staining by immunohistochemistry (IHC), or 2+ staining by IHC in conjunction with ErbB 2 gene amplification by FISH, or ErbB2 gene amplification by FISH alone (in subjects whose tumor blocks were not assessed by IHC). Subjects with tumors that are 2+ by IHC but negative by FISH assay are ineligible. ? At least one measurable lesion in the brain, defined as any lesion equal to 10 mm in longest dimension on T1-weighted, gadolinium-enhanced MRI; ? Prior treatment of brain metastases with whole brain radiotherapy (WBRT) and/or stereotactic radiosurgery (SRS); ? Unequivocal evidence of new and/or progressive lesions in the brain on an imaging study; Note: Subjects with progressive brain lesions are not required to meet RECIST criteria for CNS progression in order to be eligible for this study. ? Prior treatment with trastuzumab, either alone or in combination with chemotherapy is required. Trastuzumab must be discontinued at least 2 weeks prior to enrollment on study; ? Cardiac ejection fraction within institutional range of normal as measured by echocardiogram. MUGA scans will be accepted in cases where an echocardiogram cannot be performed or is inconclusive; ? Female subjects with child bearing potential or male subjects able to father a child must be completely abstinent from intercourse or use acceptable methods for birth control during the course of the study; ? Subjects must have normal organ and marrow function as defined below: SYSTEM LABORATORY VALUES Hematologic ANC (absolute neutrophil count) 1.0 x 109/L Hemoglobin  9 g/dL (after transfusion if needed) Platelets  50 x 109/L Hepatic Albumin  2.5 g/dL Serum bilirubin  1.5x ULN unless due to Gilbert's syndrome AST and ALT  5x ULN if documented liver metastases  3x ULN without liver metastases Renal Serum Creatinine  2.0 mg/dL or Calculated Creatinine Clearance*  25 mL/min *Calculated by the Cockcroft and Gault Method
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

? Subjects who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study or who have unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment. ? Concurrent treatment with an investigational agent or participation in another treatment clinical trial. ? Subjects receiving concurrent chemotherapy, radiation therapy, immunotherapy, biologic therapy (including an ErbB1 and/or ErbB2 inhibitor), or hormonal therapy for treatment of their cancer. Hormone therapy for ovarian suppression which has been used for > 6 months, during which time there has been disease progression in the brain, is allowed. Concurrent treatment with bisphosphonates is allowed. ? Subjects with leptomeningeal carcinomatosis as the only site of CNS involvement. ? History of allergic reactions attributed to compounds of similar chemical composition (quinazolines) to lapatinib . ? Concurrent treatment with medications that are either inducers or inhibitors of CYP3A4 is prohibited. (For important exceptions, refer to Section Error! Reference source not found., Prohibited Medications). ? Malabsorption Syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with active, uncontrolled ulcerative colitis are also excluded. ? History of immediate or delayed hypersensitivity reaction to gadolinium contrast agents, or other contraindication to gadolinium contrast. ? Other known contraindication to MRI, such as a cardiac pacemaker, implanted cardiac defibrillator, brain aneurysm clips, cochlear implant, ocular foreign body, or shrapnel. ? Pre-existing severe cerebral vascular disease, such as stroke involving a major vessel, CNS vasculitis, or malignant hypertension. ? Active cardiac disease, defined as one or more of the following: ? History of uncontrolled or symptomatic angina ? History of arrhythmias requiring medications, or clinically significant, with the exception of asymptomatic atrial fibrillation requiring anticoagulation ? Myocardial infarction < 6 months from study entry ? Uncontrolled or symptomatic congestive heart failure ? Left ventricular ejection fraction (LVEF) below the institutional normal limit ? Any other cardiac condition, which in the opinion of the treating physician, would make this protocol unreasonably hazardous for the subject ? Uncontrolled infection. ? History of other malignancy, except for curatively treated basal cell carcinoma or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix. Subjects with other malignancies who have been disease-free for at least 5 years are eligible. ? Pregnant or lactating females.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified