Breast cancer MedDRA version: 9.1 Level: LLT Classification code 10006187 Term: Breast cancer
Conditions
Interventions
Trade Name: Zometa (Zoledronic Acid)
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ZOLEDRONIC ACID
CAS Number: 1180729
Sponsors
Sheffield Teaching Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - women with histological diagnosis of invasive breast cancer - T2 tumour or above - requiring neo-adjuvant chemotheraoy in the opinion of the responsible clinician - any hormone or HER2 receptor status - over 18 years - women of child bearing potential must use reliable and appropriate method of contraception - WHO performance status of 0, 1 or 2 - patients must consent to or have undergone a core biopsy for the diagnosis of their breast cancer AND consent to undergo and additional core biopsy prior to the second cycle of chemotherapy - written informed consent 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
Exclusion criteria: - T0, T1 tumours - no previous chemotherapy or radiotherapy to the treated breast - evidence of metastatic disease or recurrent breast cancer - previous diagnosis of malignancy unless i) contralateral breast cancer off all treatments for at least 6 months prior to treatment with chemotherapy ii) disease free for 5 years iii) non-melanomatous skin cancer or carcinoma of the uterine cervix treated with curative intent - serum creatinine >1.5x upper limiit of normal reference range or calculated creatinine clearance <40 mls/min - prior treatment with bisphosphonates in the last year - concurrent tamoxifen or aromatase inhibitor medication - requiring anticoagulation with warfarin or coumarin derivatives - known hypersensitivity to bisphosphonates - current active dental problems including dental adcess or infection of the jawbone or a current or prior diagnosis of osteonecrosis of the jaw - recent (within 4 weeks) or planned dental or jaw surgery - pregnant and lactating women - cardiac dysfunction that, in the opinion of the clinician, precludes the use if anthracycline chemotherapy - males - unwilling to have interim biopsy prior to the second cycle of chemotherapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): the primary outcome measure for this study is an increase in apoptotic index between diagnostic core biopsy and repeat core biopsy taken on day 5 of study ;Main Objective: the principle objective is to study the short-term biological effects of treatment and whether the addition of zoledronic acid to combination neoadjuvant (pre-operative) chemotherapy causes additive or synergistic efects on tumour growth ininvasive breast cancer; specifically assessing apoptosis (programmed cancer cell death) and proliferation (cancer activity). It is hoped the study will determine whether the addition of zoledronic acid to neoadjuvant chemotherapy causes an increase in apoptosis between the diagnostic core biopsy and an additional core biopsy for research purposes on day 5, compared to neoadjuvant chemotherapy alone ; Secondary Objective: the secondary objectives of the study are: 1) to determine whether the addition of zoledronic acid to neoadjuvant chenotherapy casuers a reduction in proliferation between the preoperative core biopsy, the day 5 interim biopsy and the operative tumour sample, compared to neoadjuvant chemotheraoy alone. 2) to determine the pattern of expression of serum angiogenesis biomarkers (markers of new tumour blood vessel formation in the bloodstream) at randomisation, day 5, before the second cycle of chemotherapy and prior to surgery 3) to measure bone markers at randomisation, day 5, before the second cycke of chemotherapy and prior to surgery (to assess if bone turnover and activity has reduced 4) to detect the presence of circulating tumour cells in the peripheral blood (taken at randomisation, day 5, before the second cycle of chemotherapy and prior to surgery) and any changes in response to treatment | — |
Countries
United Kingdom
Outcome results
None listed