Breast CancerPhase 2ANZACNCT00525759
Investigating the Biological Effects of the Addition of Zoledronic Acid to Pre-operative Chemotherapy in Breast Cancer
A Phase 2 study testing 5-FU, Epirubicin, Cyclophosphamide, Docetaxel and 5-FU, Epirubicin, Cyclophosphamide, Docetaxel, Zoledronic acid in people with Breast Cancer, run by Sheffield Teaching Hospitals NHS Foundation Trust at 1 site in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- 5-FU, Epirubicin, Cyclophosphamide, Docetaxel and 5-FU, Epirubicin, Cyclophosphamide, Docetaxel, Zoledronic acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jul 2007to Jan 2010
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Sheffield Teaching Hospitals NHS Foundation Trust / Weston Park Hospital
Sheffield, South Yorkshire, S10 2SJ
About this study
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
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.
- Conditions
- Breast Cancer
- Being tested
- 5-FU, Epirubicin, Cyclophosphamide, Docetaxel, 5-FU, Epirubicin, Cyclophosphamide, Docetaxel, Zoledronic acid
- Keywords
- Breast cancer, Zoledronic acid, Neoadjuvant chemotherapy, Synergy, Apoptosis
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-FU, Epirubicin, Cyclophosphamide, DocetaxelDrug
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 acidDrug
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
| Study group | Role | What they receive |
|---|---|---|
| A | Active comparator | Neoadjuvant chemotherapy alone Receives: Drug: 5-FU, Epirubicin, Cyclophosphamide, Docetaxel |
| B | Experimental | Neoadjuvant chemotherapy + zoledronic acid Receives: Drug: 5-FU, Epirubicin, Cyclophosphamide, Docetaxel, Zoledronic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Increase in apoptotic index between diagnostic core biopsy and repeat core biopsy taken on day 5
Measured: Repeat biopsy on day 5 (+/- day 21)
Secondary outcomes (4)
Reduction in Ki67 immunostaining between preoperative core biopsy, repeat core biopsy on day 5, +/- day 21, and operative specimen
Measured: Day 5, +/- Day 21, surgical specimen
Changes in serum angiogenesis markers between pre-treatment and operative time points
Measured: Pre-treatment, Day 5, day 21, pre-surgery
Changes in bone biochemical markers between pre-treatment, treatment and operative timepoints
Measured: 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
Measured: Pre-treatment, day 5, day 21, pre-surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Sep 2007 (estimated)
- Study startJul 2007
- Primary completionJan 2010
- Study completionJan 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sheffield Teaching Hospitals NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University of Sheffield
- Investigators
- Robert E Coleman, MB BS, MD, Principal investigator, Academic Unit of Clinical Oncology, University of Sheffield
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00525759
- Sponsor's protocol ID
- STH14707
- Acronym
- ANZAC
- Status last verified
- Nov 2023
- First submitted
- 5 Sep 2007
- Last updated
- 24 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 11308265Neville-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.
PubMed 15455384Ottewell 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
Adams A, Jakob T, Huth A, Monsef I, Ernst M, Kopp M, Caro-Valenzuela J, Wockel A, Skoetz N. Bone-modifying agents for reducing bone loss in women with early and locally advanced breast cancer: a network meta-analysis. Cochrane Database Syst Rev. 2024 Jul 9;7(7):CD013451. doi: 10.1002/14651858.CD013451.pub2.
PubMed 38979716Winter MC, Wilson C, Syddall SP, Cross SS, Evans A, Ingram CE, Jolley IJ, Hatton MQ, Freeman JV, Mori S, Holen I, Coleman RE. Neoadjuvant chemotherapy with or without zoledronic acid in early breast cancer--a randomized biomarker pilot study. Clin Cancer Res. 2013 May 15;19(10):2755-65. doi: 10.1158/1078-0432.CCR-12-3235. Epub 2013 Mar 20.
PubMed 23515409
Study at a glance
From the registry record, last updated by the sponsor on 24 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00525759
- Acronym / sponsor ID
- ANZAC / STH14707
- Conditions
- Breast Cancer
- Keywords
- Breast cancer, Zoledronic acid, Neoadjuvant chemotherapy, Synergy, Apoptosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Sheffield Teaching Hospitals NHS Foundation TrustUniversity, hospital or other
- Collaborators
- University of Sheffield
- Study start
- Jul 2007
- Primary completion
- Jan 2010 (actual)
- Study completion
- Jan 2010 (actual)
- First posted
- 6 Sep 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Active comparator | Drug: 5-FU, Epirubicin, Cyclophosphamide, DocetaxelNeoadjuvant chemotherapy alone |
| B | Experimental | Drug: 5-FU, Epirubicin, Cyclophosphamide, Docetaxel, Zoledronic acidNeoadjuvant chemotherapy + zoledronic acid |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 5-FU, Epirubicin, Cyclophosphamide, Docetaxel3 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 | Drug | A |
| 5-FU, Epirubicin, Cyclophosphamide, Docetaxel, Zoledronic acid3 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 | Drug | B |
Primary outcome
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)
4 secondary outcomes
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
Changes in serum angiogenesis markers between pre-treatment and operative time points
Time frame: 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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Nov 2023.
- Background: PubMed 11308265Jagdev 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.
- Background: PubMed 15455384Neville-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.
- BackgroundOttewell 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
- Derived from this study: PubMed 38979716Adams A, Jakob T, Huth A, Monsef I, Ernst M, Kopp M, Caro-Valenzuela J, Wockel A, Skoetz N. Bone-modifying agents for reducing bone loss in women with early and locally advanced breast cancer: a network meta-analysis. Cochrane Database Syst Rev. 2024 Jul 9;7(7):CD013451. doi: 10.1002/14651858.CD013451.pub2.
- Derived from this study: PubMed 23515409Winter MC, Wilson C, Syddall SP, Cross SS, Evans A, Ingram CE, Jolley IJ, Hatton MQ, Freeman JV, Mori S, Holen I, Coleman RE. Neoadjuvant chemotherapy with or without zoledronic acid in early breast cancer--a randomized biomarker pilot study. Clin Cancer Res. 2013 May 15;19(10):2755-65. doi: 10.1158/1078-0432.CCR-12-3235. Epub 2013 Mar 20.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert E Coleman, MB BS, MD principal investigator
Academic Unit of Clinical Oncology, University of Sheffield
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 5-FU, Epirubicin, Cyclophosphamide, Docetaxel and 5-FU, Epirubicin, Cyclophosphamide, Docetaxel, Zoledronic acid in people with Breast Cancer, run by Sheffield Teaching Hospitals NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00525759, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Nov 2023.