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

This study has been completed.
Sponsor:
Information provided by:
Sheffield Teaching Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT00525759
First received: September 5, 2007
Last updated: November 3, 2010
Last verified: November 2010
History of Changes
  Purpose

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 Intervention Phase
Breast Cancer
 Drug: 5-FU, Epirubicin, Cyclophosphamide, Docetaxel
Drug: 5-FU, Epirubicin, Cyclophosphamide, Docetaxel, Zoledronic acid
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Sheffield Teaching Hospitals NHS Foundation Trust:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Changes in serum angiogenesis markers between pre-treatment and operative time points [ Time Frame: Pre-treatment, Day 5, day 21, pre-surgery ] [ Designated as safety issue: No ]
  • Changes in bone biochemical markers between pre-treatment, treatment and operative timepoints [ Time Frame: Pre-treatment, Day 5, day 21, pre-surgery ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 40
Study Start Date: July 2007
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00525759

Locations
United Kingdom
Sheffield Teaching Hospitals NHS Foundation Trust / Weston Park Hospital
Sheffield, South Yorkshire, United Kingdom, S10 2SJ
Sponsors and Collaborators
Sheffield Teaching Hospitals NHS Foundation Trust
Investigators
Principal Investigator: Robert E Coleman, MB BS, MD Academic Unit of Clinical Oncology, University of Sheffield
  More Information

Publications:
Ottewell PD, Jones M, Coleman RE, Holen I. Synergistic effects of cytotoxic drugs and anti-resorptive agents in vitro and in vivo. In 29th Annual San Antonio Breast Cancer Symposium Vol.100 Suppl.1 Abstract 6102, Breast Cancer Research and Treatment

Responsible Party: Director of Research & Development, Sheffield Teaching Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT00525759     History of Changes
Other Study ID Numbers: STH14707
Study First Received: September 5, 2007
Last Updated: November 3, 2010
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee
United Kingdom: National Health Service

Keywords provided by Sheffield Teaching Hospitals NHS Foundation Trust:
Breast cancer
Zoledronic acid
Neoadjuvant chemotherapy
Synergy
Apoptosis

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Fluorouracil
Docetaxel
Epirubicin
Zoledronic acid
Diphosphonates
Immunosuppressive Agents
Immunologic Factors
 Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Antimetabolites
Antimetabolites, Antineoplastic
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on May 23, 2013