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

November 3, 2010 updated by: Sheffield Teaching Hospitals NHS Foundation Trust

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • South Yorkshire
      • Sheffield, South Yorkshire, United Kingdom, S10 2SJ
        • Sheffield Teaching Hospitals NHS Foundation Trust / Weston Park Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Increase in apoptotic index between diagnostic core biopsy and repeat core biopsy taken on day 5
Time Frame: Repeat biopsy on day 5 (+/- day 21)
Repeat biopsy on day 5 (+/- day 21)

Secondary Outcome Measures

Outcome Measure
Time Frame
Reduction in Ki67 immunostaining between preoperative core biopsy, repeat core biopsy on day 5, +/- day 21, and operative specimen
Time Frame: Day 5, +/- Day 21, surgical specimen
Day 5, +/- Day 21, surgical specimen
Changes in serum angiogenesis markers between pre-treatment and operative time points
Time Frame: Pre-treatment, Day 5, day 21, pre-surgery
Pre-treatment, Day 5, day 21, pre-surgery
Changes in bone biochemical markers between pre-treatment, treatment and operative timepoints
Time Frame: Pre-treatment, Day 5, day 21, pre-surgery
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
Time Frame: Pre-treatment, day 5, day 21, pre-surgery
Pre-treatment, day 5, day 21, pre-surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sheffield Teaching Hospitals NHS Foundation Trust

Investigators

  • Principal Investigator: Robert E Coleman, MB BS, MD, Academic Unit of Clinical Oncology, University of Sheffield

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2007

Primary Completion (Actual)

January 1, 2010

Study Completion (Actual)

January 1, 2010

Study Registration Dates

First Submitted

September 5, 2007

First Submitted That Met QC Criteria

September 5, 2007

First Posted (Estimate)

September 6, 2007

Study Record Updates

Last Update Posted (Estimate)

November 4, 2010

Last Update Submitted That Met QC Criteria

November 3, 2010

Last Verified

November 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STH14707

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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