A prospective Phase II study to evaluate alterations in molecular biomarkers in HER2-positive metastatic breast cancer together with assessment of trastuzumab use beyond progression after initial exposure to trastuzumab-taxane based treatment - SHERsig

Recruitment & Eligibility

Status: ot Recruiting

Sex: Female

Target Recruitment: 50

Inclusion Criteria

1. Written and signed informed consent prior to beginning protocol-specific procedures.
2. Female patients age =18 years.
3. Evaluable with or without measurable metastatic breast cancer and at least one metastatic lesion which is amenable to multiple core biopsies.
4. HER2-positive metastatic lesion, defined as IHC3+ and/or ISH positive (FISH, CISH or SISH), as confirmed by the central laboratory testing.
5. All tumor biopsy material can be made available for central laboratory testing.
6. ECOG performance status = 2.
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

Prior or Current Treatments
1. Prior chemotherapy for metastatic disease.
2. Prior trastuzumab-based therapy for metastatic breast cancer.
3. Prior therapy with capecitabine.
4. Prior adjuvant/neoadjuvant trastuzumab, or adjuvant bevacizumab or tyrosine kinase inhibitor (TKI) completed <6 months prior to first study treatment.
5. Prior doxorubicin >360 mg/m2 or epirubicin 720 mg/m2 or equivalent.
6. Prior adjuvant taxane completed <12 months prior to first study treatment.
7. Biopsy of metastatic or breast lesion with fine needle aspiration only.
8. CNS disease as the only site of metastatic disease.
9. Use of immunotherapy or biological anticancer therapy within 21 days prior to study entry.
10. Oral or parenteral anticoagulation within 7 days prior to the baseline biopsy and/or coagulation profile outside the normal laboratory range within 48 hrs prior to the baseline biopsy.
11. Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational drug within 30 days prior to study screening.
12. Concurrent immunotherapy or anticancer hormonal therapy.

Laboratory
13. Inadequate bone marrow function: ANC < 1.5 x 109/L, platelet count < 100 x 109/L or Hb < 9 g/dL.
14. Inadequate renal function: serum creatinine > 2.0 mg/dL or 177 µmol/L.
15. Inadequate liver function:
• serum (total) bilirubin > 1.5 ULN,
• AST and ALT > 3 x ULN (>6 x ULN for patients with liver metastases),
• AST or ALT > 3 x ULN concurrent with serum alkaline phosphatase levels > 6 x ULN at baseline.

Prior or Concomitant Conditions
16. Serious concurrent disease which could affect compliance with the protocol or interpretation of results, including, but not limited to:
• Known bleeding diastheses
• Co-morbid condition which does not permit cessation of anti-platelet therapy (such as clopidigrel, aspirin) for 7 days before and after serial core biopsies
• Existing peripheral neuropathy NCI grade > 2 from any cause
• Active infection requiring antibiotics
• Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg)
• Clinically significant cardiovascular disease: Cerebrovascular accident / stroke (= 6 months prior to registration), myocardial infarction (= 6 months prior to registration), unstable angina, New York Heart Association (NYHA) Class 2 or greater congestive heart failure, serious cardiac arrhythmia requiring medication
• Dyspnoea at rest requiring supportive oxygen therapy or with significant pleural effusions
• Patients requiring chronic daily treatment with corticosteroids (dose of >10 mg/day methylprednisolone equivalent) (excluding inhaled steroids)

17. Cardiac toxicity during previous trastuzumab treatment that necessitated discontinuation of trastuzumab.
18. Left ventricular ejection fraction (LVEF) of < 50% by echocardiogram or MUGA.
19. Evidence of any other serious intercurrent disease, metabolic or psychological dysfunction, physical examination finding, or clinical laboratory finding, sociological or geographical condition which would contraindicate the use of an investigational drug, or preclude adequate follow-up and compliance with the study protocol.
20. History of another malignancy which could affect compliance with the protocol or interpretation of results. Cancer patients treated with curative intent (including for contralateral invasive or in situ breast cancer) are generally eligible if disease-free for at least 5 years, as are patients treated curatively for ca

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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