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

Breast Cancer Clinical Trial

— ANZAC  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00525759
• Other study ID #: STH14707
• Status: Completed
• Phase: Phase 2
• Start date: July 2007
• Est. completion date: January 2010

Study information

• Verified date: November 2023
• Source: Sheffield Teaching Hospitals NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: January 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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
• 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

Locations

Country	Name	City	State
United Kingdom	Sheffield Teaching Hospitals NHS Foundation Trust / Weston Park Hospital	Sheffield	South Yorkshire

Sponsors (2)

Lead Sponsor	Collaborator
Sheffield Teaching Hospitals NHS Foundation Trust	University of Sheffield

Country where clinical trial is conducted

United Kingdom, 

References & Publications (3)

Jagdev SP, Coleman RE, Shipman CM, Rostami-H A, Croucher PI. The bisphosphonate, zoledronic acid, induces apoptosis of breast cancer cells: evidence for synergy with paclitaxel. Br J Cancer. 2001 Apr 20;84(8):1126-34. doi: 10.1054/bjoc.2001.1727. — View Citation

Neville-Webbe HL, Rostami-Hodjegan A, Evans CA, Coleman RE, Holen I. Sequence- and schedule-dependent enhancement of zoledronic acid induced apoptosis by doxorubicin in breast and prostate cancer cells. Int J Cancer. 2005 Jan 20;113(3):364-71. doi: 10.1002/ijc.20602. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Increase in apoptotic index between diagnostic core biopsy and repeat core biopsy taken on day 5		Repeat biopsy on day 5 (+/- day 21)
Secondary	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
Secondary	Changes in serum angiogenesis markers between pre-treatment and operative time points		Pre-treatment, Day 5, day 21, pre-surgery
Secondary	Changes in bone biochemical markers between pre-treatment, treatment and operative timepoints		Pre-treatment, Day 5, day 21, pre-surgery
Secondary	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