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Breast CancerPhase 3NCT00072020

Chemotherapy and/or Hormone Therapy With or Without Zoledronate in Treating Women With Stage II or Stage III Breast Cancer

A Phase 3 study testing zoledronic acid, adjuvant therapy and neoadjuvant therapy in people with Breast Cancer and Metastatic Cancer, run by University of Sheffield.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

RATIONALE: Zoledronate may delay or prevent the formation of bone metastases. It is not yet known whether chemotherapy and/or hormone therapy are more effective with or without zoledronate in preventing cancer recurrence and bone metastases in women with breast cancer. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer, Metastatic Cancer
What is being tested?
zoledronic acid, adjuvant therapy and neoadjuvant therapy
Type of treatment
Surgery or procedure
How many people
Not given
Where
No sites listed yet
Study dates
Aug 2003to not given
Phase
Phase 3
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

DISEASE CHARACTERISTICS:

  • Diagnosis of primary breast cancer, meeting 1 of the following staging criteria:
  • Stage II
  • Stage III
  • T stage ≥ T1
  • Receiving OR scheduled to receive chemotherapy and/or endocrine therapy
  • For patients receiving neoadjuvant therapy
  • Tumor > 5 cm (T3), features of locally advanced disease (T4), OR biopsy-proven lymph node involvement (N1)
  • Scheduled to proceed to definitive surgery and/or radical radiotherapy with curative intent within 6 months of starting neoadjuvant therapy
  • No more than 30 days between initiation of neoadjuvant therapy and start of study drug
  • For patients receiving adjuvant therapy
  • Must have undergone complete primary tumor resection and treatment of axillary lymph nodes*
  • Must have lymph node involvement
  • No prior neoadjuvant therapy**
  • No more than 60 days since prior definitive surgery NOTE: *Patients whose treatment plan includes further primary tumor resection and/or treatment of the axillary lymph nodes (e.g., clearance or radiotherapy) with curative intent after completion of chemotherapy are eligible provided the treatment is completed within 9 months of study entry

NOTE: **Preoperative endocrine therapy with a duration of < 30 days is not considered prior neoadjuvant therapy

  • No evidence of recurrent or metastatic disease
  • No history of breast cancer, except ductal carcinoma in situ or lobular carcinoma in situ
  • Hormone receptor status:
  • Not specified

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Sex

  • Female

Menopausal status

  • Premenopausal or postmenopausal

Performance status

  • Karnofsky 80-100% OR
  • ECOG 0-1

Life expectancy

  • Not specified

Hematopoietic

  • Not specified

Hepatic

  • Not specified

Renal

  • Creatinine ≤ 1.5 times upper limit of normal

Other

  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No active dental problems, including dental abscess or infection of the jaw bone (e.g., maxilla or mandible)
  • No prior or current diagnosis of osteonecrosis of the jaw
  • No other malignancy within the past 5 years (including prior contralateral breast cancer) except nonmelanoma skin cancer or curatively treated carcinoma in situ of the cervix
  • No history of disease with influence on bone metabolism, including any of the following:
  • Paget's disease of the bone
  • Primary hyperparathyroidism
  • Osteoporosis requiring treatment or likely to require treatment within the next 6 months
  • No other severe physical or psychological disease that would preclude study compliance
  • No known hypersensitivity to bisphosphonates

PRIOR CONCURRENT THERAPY:

Chemotherapy

  • See Disease Characteristics

Endocrine therapy

  • See Disease Characteristics

Radiotherapy

  • See Disease Characteristics

Surgery

  • See Disease Characteristics
  • More than 4 weeks since prior and no concurrent dental or jaw surgery (e.g., extractions or implants)
  • Dental fillings, teeth scaling and polishing, or minor gingival surgery within the past 4 weeks are allowed

Other

  • More than 1 year since prior bisphosphonates
  • More than 30 days since prior investigational drugs
  • No concurrent investigational drugs (i.e., not locally approved for any indication)

About this study

Official title: Does Adjuvant Zoledronic Acid Reduce Recurrence in Patients With High Risk Localized Breast Cancer?

RATIONALE: Zoledronate may delay or prevent the formation of bone metastases. It is not yet known whether chemotherapy and/or hormone therapy are more effective with or without zoledronate in preventing cancer recurrence and bone metastases in women with breast cancer.

PURPOSE: This randomized phase III trial is studying giving chemotherapy and/or hormone therapy together with zoledronate to see how well they work compared to chemotherapy and/or hormone therapy alone in preventing cancer recurrence and bone metastases in women with stage II or stage III breast cancer.

Read the detailed description

OBJECTIVES:

Primary

  • Compare disease-free survival of women with stage II or III breast cancer at high risk of relapse treated with neoadjuvant or adjuvant chemotherapy and/or hormonal therapy with vs without zoledronate.

Secondary

  • Compare time to bone metastases, as first recurrence, in patients treated with these regimens.
  • Compare time to bone metastases, per se, in patients treated with these regimens.
  • Compare time to distant metastases in patients treated with these regimens.
  • Compare overall survival in patients treated with these regimens.
  • Compare the reduction in skeletal-related events (fractures, spinal cord compression, radiotherapy to the bone, surgery to the bone, and hypercalcemia) before and after the development of bone metastases in patients treated with these regimens.
  • Determine the safety and toxicity of zoledronate in patients treated with these regimens.
  • Correlate prognostic factors, such as estrogen-receptor and progesterone-receptor status, TNM stage, tumor grade, HER2/neu status, and menopausal status with treatment outcome in patients treated with these regimens.
  • Determine more specific prognostic indicators for the development of bone metastases and factors that are able to predict specific benefit from bisphosphonate treatment using proteomics, tissue micro-array, and other modern techniques in these patients.

OUTLINE: This is a randomized, open-label, parallel-group, multicenter study. Patients are stratified according to participating center. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive neoadjuvant or adjuvant chemotherapy and/or hormonal therapy. Patients also receive concurrent zoledronate IV over 15 minutes every 3-4 weeks for 6 doses, every 3 months for 8 doses, and then every 6 months for 5 doses in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive neoadjuvant or adjuvant chemotherapy and/or hormonal therapy alone.

After completion of study treatment, patients are followed annually for 5 years.

PROJECTED ACCRUAL: A total of 3,300 patients (1,650 per treatment arm) will be accrued for this study within 3 years.

Keywords
bone metastases, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer
Medical subject headings
Breast Neoplasms, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Disease-free survival as assessed annually for 10 years

Secondary outcomes (9)

  1. Time to bone metastases as first recurrence assessed annually for 10 years

  2. Time to bone metastases per se as assessed annually for 10 years

  3. Time to distant metastases as assessed annually for 10 years

  4. Overall survival as assessed by final analysis at 10 years

  5. Skeletal-related events prior to development of bone metastases as assessed annually for 10 years

  6. Skeletal-related events following development of bone metastases as assessed annually for 10 years

  7. Safety and toxicity of zoledronic acid as assessed annually for 10 years

  8. Evaluation of the influence of prognostic factors (e.g., estrogen receptor or progesterone receptor [ER/PR] status, TNM stage, tumor grade, HER2/neu, and menopausal status) on treatment outcome

  9. Analysis of tumor-specific mutations, proteomics and gene expression changes in tumor cells

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Nov 2003 (estimated)
  2. Study startAug 2003

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Masking
None (open label)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00072020
Sponsor's protocol ID
SHEFF-AZURE
Other IDs
CDR0000335111, EU-20315, ISRCTN79831382, BIG-1-04
Status last verified
Jan 2006
First submitted
4 Nov 2003
Last updated
2 Aug 2013
Results posted
No

Publications

  • Marshall H, Gregory W, Bell R, et al.: Adjuvant therapy with zoledronic acid (AZURE-BIG 01/04): The influence of menopausal status and age on treatment effects. [Abstract] J Clin Oncol 30 (Suppl 15): A-502, 2012.

  • Coleman RE, Marshall H, Cameron D, Dodwell D, Burkinshaw R, Keane M, Gil M, Houston SJ, Grieve RJ, Barrett-Lee PJ, Ritchie D, Pugh J, Gaunt C, Rea U, Peterson J, Davies C, Hiley V, Gregory W, Bell R; AZURE Investigators. Breast-cancer adjuvant therapy with zoledronic acid. N Engl J Med. 2011 Oct 13;365(15):1396-405. doi: 10.1056/NEJMoa1105195. Epub 2011 Sep 25.

    PubMed 21995387

  • Coleman R, Woodward E, Brown J, Cameron D, Bell R, Dodwell D, Keane M, Gil M, Davies C, Burkinshaw R, Houston SJ, Grieve RJ, Barrett-Lee PJ, Thorpe H. Safety of zoledronic acid and incidence of osteonecrosis of the jaw (ONJ) during adjuvant therapy in a randomised phase III trial (AZURE: BIG 01-04) for women with stage II/III breast cancer. Breast Cancer Res Treat. 2011 Jun;127(2):429-38. doi: 10.1007/s10549-011-1429-y. Epub 2011 Mar 11.

    PubMed 21394500

  • Coleman RE, Winter MC, Cameron D, Bell R, Dodwell D, Keane MM, Gil M, Ritchie D, Passos-Coelho JL, Wheatley D, Burkinshaw R, Marshall SJ, Thorpe H; AZURE (BIG01/04) Investigators. The effects of adding zoledronic acid to neoadjuvant chemotherapy on tumour response: exploratory evidence for direct anti-tumour activity in breast cancer. Br J Cancer. 2010 Mar 30;102(7):1099-105. doi: 10.1038/sj.bjc.6605604. Epub 2010 Mar 16.

    PubMed 20234364

  • Coleman R, Thorpe H, Cameron D, et al.: Zoledronic acid is well tolerated and can be safely administered with adjuvant chemotherapy first safety data from the AZURE trial (BIG01/04). [Abstract] Breast Cancer Res Treat 100 (Suppl 1): A-2080, S107, 2006.

  • 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 38979716

  • Coleman R, Cameron D, Dodwell D, Bell R, Wilson C, Rathbone E, Keane M, Gil M, Burkinshaw R, Grieve R, Barrett-Lee P, Ritchie D, Liversedge V, Hinsley S, Marshall H; AZURE investigators. Adjuvant zoledronic acid in patients with early breast cancer: final efficacy analysis of the AZURE (BIG 01/04) randomised open-label phase 3 trial. Lancet Oncol. 2014 Aug;15(9):997-1006. doi: 10.1016/S1470-2045(14)70302-X. Epub 2014 Jul 15.

    PubMed 25035292

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing zoledronic acid, adjuvant therapy and neoadjuvant therapy in people with Breast Cancer and Metastatic Cancer, run by University of Sheffield.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

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: status not confirmed, as of the sponsor's last update on 2 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.

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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

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?

Disease-free survival as assessed annually for 10 years. 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 NCT00072020, which also lists 7 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 2 Aug 2013; AzTrials last refreshed its copy on 6 Nov 2026.

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