A Study of Lapatinib for Brain Metastases in Subjects with ErbB2-Positive Breast Cancer Following Trastuzumab Therapy and Cranial Radiotherapy

Phase 1

• Conditions: Progressive symptomatic or asymptomatic ErbB2 overexpressing breast cancer brain metastases.; MedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000020826; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2005-003944-68-DE
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-12-28
• Last Update Posted: 2 October 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 220

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 ErbB 2 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 >or= 10mm in longest dimension on T1-weighted, gadolinium-enhanced MRI;
Prior treatment of brain metastases with WBRT and/or 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 will 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;
At least 2 weeks since prior radiotherapy, last chemotherapy, immunotherapy, biologic therapy, or hormonal therapy for cancer, and sufficiently recovered or stabilized from side effects associated with prior therapy. Concurrent treatment with bisphosphonates is permitted;
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 in the protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 188
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 56

Exclusion Criteria

1. 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;
2. Concurrent treatment with an investigational agent or participation in another treatment clinical trial;
3. 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;
4. Subjects with leptomeningeal carcinomatosis as the only site of CNS involvement;
5. History of allergic reactions attributed to compounds of similar chemical
composition (quinazolines) to lapatinib;
6. Concurrent treatment with medications that are either inducers or inhibitors of CYP3A4 is prohibited. (For important exceptions, refer to Section 8.2, Prohibited Medications);
7. Malabsorption Syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with active, uncontrolled ulcerative colitis are also excluded;
8. History of immediate or delayed hypersensitivity reaction to gadolinium contrast
agents, or other contraindication to gadolinium contrast;
9. Other known contraindication to MRI, such as a cardiac pacemaker, implanted cardiac defibrillator, brain aneurysm clips, cochlear implant, ocular foreign body, or shrapnel;
10. Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical or psychiatric disorder that would interfere with the subject's safety;
11. Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent;
12. Pre-existing severe cerebral vascular disease, such as stroke involving a major vessel, CNS vasculitis, or malignant hypertension;
13. 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
? Ejection fraction 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 patient
14. Uncontrolled infection;
15. 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;
16. Pregnant or lactating females.

Study & Design

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