A phase II open label, multicenter study to evaluate the efficacy and safety of daily dose of Lapatinib in advanced breast cancer patients with HER-2 non-amplified primary tumours and HER-2 positive circulating tumour cells or EGFR positive circulating tumor cells

Phase 1

Conditions: Advanced breast cancer patients with HER-2 non-amplified primary tumours and HER-2 positive circulating tumour cells or EGFR positive circulating tumour cells
MedDRA version: 9.1 Level: LLT Classification code 10057654 Term: Breast cancer female

Registration Number: EUCTR2007-002155-17-GB

Lead Sponsor: GlaxoSmithKline Research and Development Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 0

Inclusion Criteria

1. Signed written informed consent
2. Female patients, age = 18 years
3. Histologically confirmed diagnosis of HER-2 negative (i.e. no gene amplification by FISH or IHC 2+ and no amplification by FISH or IHC 0/1+) infiltrating primary breast cancer.
4. Evidence of EGFR positive circulating tumour cells or HER-2 positive (=50% CTCs or FISH positive) in a peripheral blood sample taken at screening visit.
5. Metastatic disease with at least one measurable lesion as per RECIST criteria classification
6. No brain metastasis requiring local therapy. Stable or asymptomatic subjects are allowed.
7. Availability of tumour block or at least six unstained 4 µm sections of the primary
tumour to be sent to the central lab after eligibility confirmation for HER-2 central testing by FISH.
8. Eastern Cooperative Oncology Group (ECOG) score for performance status 0 to 3
9. Life expectancy > 12 weeks
10. Adequate baseline haematologic, hepatic and renal function at screening visit.
11. Normal left ventricular ejection fraction (LVEF) by echocardiogram or MUGA.
12. Negative serum pregnancy test (only in childbearing potential female)
13. Patients with reproductive potential needs consistent and correct use of adequate non-hormonal methods of birth control (barrier methods or intrauterine device)
14. Previous treatment with anthracyclines and/or taxanes in the neo-adjuvant,
adjuvant or advanced setting
15. At least one line of treatment for metastatic disease
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Any unstable systemic disease including active infections, significant cardiovascular disease, as well as myocardial infarction within the previous year, any significant hepatic (current active hepatic or biliary disease [with exception of patients with Gilbert's syndrome, asymtomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment]), renal or metabolic disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of study medication or that might affect the interpretation of the results or render the patient at high risk from treatment complications.
2. Pregnant or lactating women
3. Dementia, altered mental status, or any psychiatric condition that could prohibit the understanding or rendering of informed consent
4. Lack of physical integrity of the upper gastrointestinal (GI) tract, poor absorption
of the GI tract or inability to take oral medication
5. Other co-existing malignancy or malignancies within the last 5 years with the
exception of basal cell carcinoma or in-situ carcinoma
6. Concurrent anti-cancer therapies (chemo or hormonal therapy) other than study drug
7. Concurrent treatment with an investigational agent or participation in any investigational drug study within 4 weeks preceding treatment start
8. Concurrent radiotherapy to the only target lesion. Concurrent bisphosphonates are allowed as long as this therapy has started before patient receives study medication.
9. Previous treatment with anti HER-2 or anti-EGFR therapies
10. Protocol specified treatment regimens that would be inappropriate for the
management of the subject (See also concomitant medication Section 7.9).

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of a daily dose of lapatinib in advanced breast cancer patients with HER-2 non-amplified primary tumours with HER-2 or EGFR positive circulating tumour cells.;<br> Secondary Objective: • To evaluate anti-tumour activitiy of lapatinib<br> • To evaluate the safety of lapatinib<br> • To determine the early response of lapatinib on proliferation and the MAP kinase cascade by PET in a substudy in patients with EGFR positive CTCs only.<br><br> The translational research objective is to correlate response to lapatinib with HER-2 and EGFR protein levels and amplification evaluated on CTCs before starting treatment. A centralized review of the HER-2 status on the primary tumour will be performed retrospectively.<br> ;<br> Primary end point(s): The primary endpoint for the analysis is to evaluate the overall response rate (ORR)<br> according to RECIST criteria.<br>

Secondary Outcome Measures

Name	Time	Method

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