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

NCT00072020 | Unknown Phase 3

• 5 other identifiers: SHEFF-AZURECDR0000335111EU-20315ISRCTN79831382BIG-1-04
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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. 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.

Conditions

Breast Cancer; Metastatic Cancer

Keywords

bone metastases; stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer

Outcome Measures

Primary Outcomes (1)

• Disease-free survival as assessed annually for 10 years

Secondary Outcomes (9)

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

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

• Time to distant metastases as assessed annually for 10 years

• Overall survival as assessed by final analysis at 10 years

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

Interventions

zoledronic acid DRUG

adjuvant therapy PROCEDURE

neoadjuvant therapy PROCEDURE

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of Sheffield: lead

Related Publications (7)

• 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.

  RESULT

• 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.

  PMID: 21995387 RESULT

• 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.

  PMID: 21394500 RESULT

• 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.

  PMID: 20234364 RESULT

• 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.

  RESULT

• 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.

  PMID: 38979716 DERIVED

• 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.

  PMID: 25035292 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

Zoledronic Acid; Chemotherapy, Adjuvant; Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Combined Modality Therapy; Therapeutics; Drug Therapy

Study Officials

• Robert E. Coleman, MD, FRCP

  Cancer Research Centre at Weston Park Hospital

• Victoria Hiley

  University of Leeds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: November 4, 2003
• First Posted: November 6, 2003
• Study Start: August 1, 2003
• Last Updated: August 2, 2013

Record last verified: 2006-01