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

Phase 2

Completed

• Conditions: Breast Cancer
• Interventions: Drug: 5-FU, Epirubicin, Cyclophosphamide, Docetaxel; Drug: 5-FU, Epirubicin, Cyclophosphamide, Docetaxel, Zoledronic acid

• Registration Number: NCT00525759
• Lead Sponsor: Sheffield Teaching Hospitals NHS Foundation Trust

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2007-07
• Study First Submitted: 2007-09-05
• Study First Submitted QC: 2007-09-05
• Study First Posted: 2007-09-06
• Primary Completion: 2010-01
• Study Completion: 2010-01
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-21
• Last Update Posted: 2023-11-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 40

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A	5-FU, Epirubicin, Cyclophosphamide, Docetaxel	Neoadjuvant chemotherapy alone
B	5-FU, Epirubicin, Cyclophosphamide, Docetaxel, Zoledronic acid	Neoadjuvant chemotherapy + zoledronic acid

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (1)

Sheffield Teaching Hospitals NHS Foundation Trust / Weston Park Hospital; 🇬🇧 Sheffield, South Yorkshire, United Kingdom