ANZAC: Investigating the Biological Effects of the Addition of Zoledronic Acid to Pre-operative Chemotherapy in Breast Cancer

Sponsor

Sheffield Teaching Hospitals NHS Foundation Trust (Other)

Overall Status

Completed

CT.gov ID

NCT00525759

Collaborator

(none)

Enrollment

Location

Arms

30.1

Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

There is clear preclinical in vitro and in vivo evidence of sequence dependent synergy between chemotherapy agents and zoledronic acid. The aim of the study is to investigate if the synergistic increase in tumour cell apoptosis observed in preclinical studies occurs in patients. The hypothesis for this study is that there may be anti-tumour benefits of the sequential application of chemotherapy agents followed by zoledronic acid in patients with invasive breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: 5-FU, Epirubicin, Cyclophosphamide, Docetaxel Drug: 5-FU, Epirubicin, Cyclophosphamide, Docetaxel, Zoledronic acid	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomised Phase II Feasibility Study Investigating the Biological Effects of the Addition of Zoledronic Acid to Neoadjuvant Combination Chemotherapy on Invasive Breast Cancer

Study Start Date :

Jul 1, 2007

Actual Primary Completion Date :

Jan 1, 2010

Actual Study Completion Date :

Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: A Neoadjuvant chemotherapy alone	Drug: 5-FU, Epirubicin, Cyclophosphamide, Docetaxel 3 cycles of FEC q3w, followed by 3 cycles of docetaxel q3w FEC: 5FU 500mg/m2 intravenous bolus D1, Epirubicin 100mg/m2 intravenous bolus D1, Cyclophosphamide 500mg/m2 intravenous bolus D1) every 21 days Docetaxel: (100mg/ m2 intravenous infusion) every 21 days
Experimental: B Neoadjuvant chemotherapy + zoledronic acid	Drug: 5-FU, Epirubicin, Cyclophosphamide, Docetaxel, Zoledronic acid 3 cycles of FEC q3w, followed by 3 cycles of docetaxel q3w FEC: 5FU 500mg/m2 intravenous bolus D1, Epirubicin 100mg/m2 intravenous bolus D1, Cyclophosphamide 500mg/m2 intravenous bolus D1) every 21 days Docetaxel: (100mg/ m2 intravenous infusion) every 21 days Zoledronic acid: 4mg intravenous infusion Day 2, AFTER FIRST CYCLE CHEMOTHERAPY ONLY

Arm

Intervention/Treatment

Active Comparator: A

Neoadjuvant chemotherapy alone

Drug: 5-FU, Epirubicin, Cyclophosphamide, Docetaxel

3 cycles of FEC q3w, followed by 3 cycles of docetaxel q3w FEC: 5FU 500mg/m2 intravenous bolus D1, Epirubicin 100mg/m2 intravenous bolus D1, Cyclophosphamide 500mg/m2 intravenous bolus D1) every 21 days Docetaxel: (100mg/ m2 intravenous infusion) every 21 days

Experimental: B

Neoadjuvant chemotherapy + zoledronic acid

Drug: 5-FU, Epirubicin, Cyclophosphamide, Docetaxel, Zoledronic acid

Outcome Measures

Primary Outcome Measures

Increase in apoptotic index between diagnostic core biopsy and repeat core biopsy taken on day 5 [Repeat biopsy on day 5 (+/- day 21)]

Secondary Outcome Measures

Reduction in Ki67 immunostaining between preoperative core biopsy, repeat core biopsy on day 5, +/- day 21, and operative specimen [Day 5, +/- Day 21, surgical specimen]
Changes in serum angiogenesis markers between pre-treatment and operative time points [Pre-treatment, Day 5, day 21, pre-surgery]
Changes in bone biochemical markers between pre-treatment, treatment and operative timepoints [Pre-treatment, Day 5, day 21, pre-surgery]
Detection of, and changes in, circulating tumour cells in peripheral blood taken pre-treatment, during treatment and following treatment [Pre-treatment, day 5, day 21, pre-surgery]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Women with histological diagnosis of invasive breast cancer requiring neoadjuvant chemotherapy
T2 tumour or above
WHO Performance status of 0,1 or 2
Must consent to or have undergone a core biopsy for diagnosis of breast cancer AND consent to undergo an additional core biopsy prior to the second cycle of chemotherapy (Day 5 +/- Day 21)
Written informed consent

Exclusion Criteria:

Previous chemotherapy or radiotherapy to treated breast
Evidence of metastatic disease or recurrent breast cancer or previous malignancy (some exceptions)
Calculated creatinine clearance < 40mls/min
Prior treatment with bisphosphonates in last year or known contraindications to bisphosphonate therapy
Concurrent tamoxifen or aromatase inhibitor medication
Pregnant or lactating women
Cardiac dysfunction that precludes use of anthracycline chemotherapy
Unwilling to have extra interim biopsy