HER2 negative invasive breast cancer
Conditions
Sponsors
Cambridge University Hospitals NHS Foundation Trust
University of Cambridge
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients with histological diagnosis of HER2 negative invasive breast cancer. • UNIFOCAL TUMOUR : - T2 or T3 tumours (radiological size > or = 20 mm). - T4 tumour of any size with direct extension to (a) chest wall or (b) skin. OR Inflammatory carcinoma with tumour of any size. OR • OTHER LOCALLY ADVANCED DISEASE: - Involvement of large or fixed axillary lymph nodes (radiological diameter >20 mm or clinical N2) and primary breast tumour of any diameter. - Where no primary breast tumour was found, the presence of breast cancer in a lymph node (LN) must be histopathologically confirmed by LN biopsy (trucut or whole LN). OR • MULTIFOCAL TUMOURS: - The sum of each tumours’ maximum diameter must be > OR = 20mm (total radiological tumour size > 20mm). - Patients with bilateral disease are eligible to enter the trial. - Any hormone receptor status. - Patient fit to receive the trial chemotherapy regimen - Patient must not have clinically significant cardiac abnormalities and must not have had a previous myocardial infarction during the 6 months prior to recruitment. Cardiac function should be assessed by physical examination and by baseline measurement of LVEF. - Patient must have adequate bone marrow, hepatic, and renal function.* - ECOG performance status of 0, 1, or 2 - No previous chemotherapy or endocrine therapy. - No previous diagnosis of malignancy unless: managed by surgical or radiological treatment only, and disease-free for 10 years, or previous basal cell carcinoma, cervical carcinoma in situ or ductal carcinoma in situ of the breast treated by surgery only. - Non-pregnant and non-lactating, with no intention of pregnancy during chemotherapy, and prepared to adopt adequate barrier contraceptive measures if there is any possibility of pregnancy (males and females). - No concomitant medical or psychiatric problems that might prevent completion of treatment or follow-up. - 18 years or older - Male or female - Written informed consent for the study. - Randomisation is recommended within 4 weeks of biopsy and chemotherapy should start 1 week after randomisation - Availability of paraffin embedded tumour blocks, from pre-chemotherapy biopsy and from surgical specimen, with corresponding slides, is required. - Adequate hepatic function defined as - AST/ALT 100xunits/L - Prothrombin time (PT) and Partial thromboplastin time (PTT/ aPTT) =1.5xULN. Are the trial subjects under 18? no Number of subjects for this
Exclusion criteria
Exclusion criteria: •HER2 positive invasive breast cancer (IHC 3+ or FISH positive) •T0 and T1 tumours in absence of large (total tumour size >20mm) or fixed axillary nodes •Evidence of metastatic disease. •Prior diagnosis of ishaemic heart disease, cerebrovascular disease, peripheral vascular disease, arterial or venous thromboembolic disease, cardiac failure •Prior diagnosis of gastroduodenal ulcer, symptomatic diverticulitis, inflammatory bowel disease. •Bleeding diathesis. •On therapeutic full dose of anti-coagulants, aspirin, clopidogrel or corticosteroids •Uncontrolled hypertension defined by a systolic pressure >150mmHg and/or diastolic pressure >90mmHg, with or without anti-hypertensive medication. Patients with initial blood pressure elevations are eligible if initiation or adjustment of antihypertensive medication lowers pressure to meet entry criteria. •Presence of active uncontrolled infection •History of nephritic or nephrotic syndrome •Major surgical procedure or traumatic injury within 28 days prior to randomisation. •Any evidence of other disease which in the opinion of the investigator places the patient at high risk of treatment related complication. •Any concomitant medical or psychiatric problems which in the opinion of the investigator would prevent completion of treatment or follow-up. •Non-healing wound, or peptic ulcer, or bone fracture. •On LHRH-agonists for ER strongly positive disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Complete pathological response (pathCR) rates (tumour and lymph nodes) after neoadjuvant chemotherapy defined as no residual invasive carcinoma within the breast (DCIS permitted) AND no evidence of metastatic disease within the lymph nodes.;Timepoint(s) of evaluation of this end point: We aim to have completed analysis of the primary endpoint within 3 years of recruitment completion.;Main Objective: To determine if patients with HER2 negative early breast cancer receiving a standard regimen of neo-adjuvant chemotherapy with Avastin show better rates of complete pathological response.; Secondary Objective: •Disease-Free Survival •Overall Survival •Rate of breast conservation •pathCR rate in breast alone •Safety and toxicity | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Disease-Free Survival • Overall Survival • pathCR rate in breast alone • Radiological (ultrasound) response after 3 and after 6 cycles of chemotherapy. • Rate of breast conservation • Toxicities and safety ;Timepoint(s) of evaluation of this end point: We aim to have completed analysis of the secondary endpoints within 3 years of recruitment completion. | — |
Countries
United Kingdom
Outcome results
None listed