Clinical trial · Interventional
Investigating the Biological Effects of the Addition of Zoledronic Acid to Pre-operative Chemotherapy in Breast Cancer
A Randomised Phase II Feasibility Study Investigating the Biological Effects of the Addition of Zoledronic Acid to Neoadjuvant Combination Chemotherapy on Invasive Breast Cancer
NCT00525759CI-TRIAL-00071660ANZACcompletedPhase 2ClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Breast Cancer | Malignant Breast Neoplasm | CURATED_EXACT | 0.92 |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| 5-FU, Epirubicin, Cyclophosphamide, Docetaxel | Drug | — | UNRESOLVED |
| 5-FU, Epirubicin, Cyclophosphamide, Docetaxel, Zoledronic acid | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- type
- ACTIVE_COMPARATOR
- label
- A
- description
- Neoadjuvant chemotherapy alone
- interventionNames
- Drug: 5-FU, Epirubicin, Cyclophosphamide, Docetaxel
- type
- EXPERIMENTAL
- label
- B
- description
- Neoadjuvant chemotherapy + zoledronic acid
- interventionNames
- Drug: 5-FU, Epirubicin, Cyclophosphamide, Docetaxel, Zoledronic acid
Primary outcomes (1)
- measure
- Increase in apoptotic index between diagnostic core biopsy and repeat core biopsy taken on day 5
- timeFrame
- Repeat biopsy on day 5 (+/- day 21)
Eligibility
Eligibility (as posted)
- Sex
- Female
- Minimum age
- 18 Years
Show eligibility criteria text
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
References
Publications (5)
- BACKGROUNDJagdev 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. PMID 11308265
- BACKGROUNDNeville-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. PMID 15455384
- 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
- DERIVEDAdams 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. PMID 38979716
- DERIVEDWinter 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. PMID 23515409