Ignite Creation Date:
2025-12-25 @ 4:07 AM
Ignite Modification Date:
2025-12-26 @ 3:04 AM
Study NCT ID:
NCT00072020
Status:
UNKNOWN
Last Update Posted:
2013-08-02
First Post:
2003-11-04
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Chemotherapy and/or Hormone Therapy With or Without Zoledronate in Treating Women With Stage II or Stage III Breast Cancer
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D001943', 'term': 'Breast Neoplasms'}, {'id': 'D009362', 'term': 'Neoplasm Metastasis'}], 'ancestors': [{'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D001941', 'term': 'Breast Diseases'}, {'id': 'D012871', 'term': 'Skin Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}, {'id': 'D009385', 'term': 'Neoplastic Processes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077211', 'term': 'Zoledronic Acid'}, {'id': 'D017024', 'term': 'Chemotherapy, Adjuvant'}, {'id': 'D020360', 'term': 'Neoadjuvant Therapy'}], 'ancestors': [{'id': 'D004164', 'term': 'Diphosphonates'}, {'id': 'D063065', 'term': 'Organophosphonates'}, {'id': 'D009943', 'term': 'Organophosphorus Compounds'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D007093', 'term': 'Imidazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D003131', 'term': 'Combined Modality Therapy'}, {'id': 'D013812', 'term': 'Therapeutics'}, {'id': 'D004358', 'term': 'Drug Therapy'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT'}}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'ACTIVE_NOT_RECRUITING', 'startDateStruct': {'date': '2003-08'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2006-01', 'lastUpdateSubmitDate': '2013-08-01', 'studyFirstSubmitDate': '2003-11-04', 'studyFirstSubmitQcDate': '2003-11-05', 'lastUpdatePostDateStruct': {'date': '2013-08-02', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2003-11-06', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Disease-free survival as assessed annually for 10 years'}], 'secondaryOutcomes': [{'measure': 'Time to bone metastases as first recurrence assessed annually for 10 years'}, {'measure': 'Time to bone metastases per se as assessed annually for 10 years'}, {'measure': 'Time to distant metastases as assessed annually for 10 years'}, {'measure': 'Overall survival as assessed by final analysis at 10 years'}, {'measure': 'Skeletal-related events prior to development of bone metastases as assessed annually for 10 years'}, {'measure': 'Skeletal-related events following development of bone metastases as assessed annually for 10 years'}, {'measure': 'Safety and toxicity of zoledronic acid as assessed annually for 10 years'}, {'measure': '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'}, {'measure': 'Analysis of tumor-specific mutations, proteomics and gene expression changes in tumor cells'}]}, 'conditionsModule': {'keywords': ['bone metastases', 'stage II breast cancer', 'stage IIIA breast cancer', 'stage IIIB breast cancer', 'stage IIIC breast cancer'], 'conditions': ['Breast Cancer', 'Metastatic Cancer']}, 'referencesModule': {'references': [{'type': 'RESULT', 'citation': '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.'}, {'pmid': '21995387', 'type': 'RESULT', 'citation': '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': '21394500', 'type': 'RESULT', 'citation': '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': '20234364', 'type': 'RESULT', 'citation': '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.'}, {'type': 'RESULT', 'citation': '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.'}, {'pmid': '38979716', 'type': 'DERIVED', 'citation': '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': '25035292', 'type': 'DERIVED', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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.\n\nPURPOSE: 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.', 'detailedDescription': 'OBJECTIVES:\n\nPrimary\n\n* 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.\n\nSecondary\n\n* Compare time to bone metastases, as first recurrence, in patients treated with these regimens.\n* Compare time to bone metastases, per se, in patients treated with these regimens.\n* Compare time to distant metastases in patients treated with these regimens.\n* Compare overall survival in patients treated with these regimens.\n* 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.\n* Determine the safety and toxicity of zoledronate in patients treated with these regimens.\n* 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.\n* 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.\n\nOUTLINE: 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.\n\n* 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.\n* Arm II: Patients receive neoadjuvant or adjuvant chemotherapy and/or hormonal therapy alone.\n\nAfter completion of study treatment, patients are followed annually for 5 years.\n\nPROJECTED ACCRUAL: A total of 3,300 patients (1,650 per treatment arm) will be accrued for this study within 3 years.'}, 'eligibilityModule': {'sex': 'FEMALE', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "DISEASE CHARACTERISTICS:\n\n* Diagnosis of primary breast cancer, meeting 1 of the following staging criteria:\n\n * Stage II\n * Stage III\n * T stage ≥ T1\n* Receiving OR scheduled to receive chemotherapy and/or endocrine therapy\n\n * For patients receiving neoadjuvant therapy\n\n * Tumor \\> 5 cm (T3), features of locally advanced disease (T4), OR biopsy-proven lymph node involvement (N1)\n * Scheduled to proceed to definitive surgery and/or radical radiotherapy with curative intent within 6 months of starting neoadjuvant therapy\n * No more than 30 days between initiation of neoadjuvant therapy and start of study drug\n * For patients receiving adjuvant therapy\n\n * Must have undergone complete primary tumor resection and treatment of axillary lymph nodes\\*\n * Must have lymph node involvement\n * No prior neoadjuvant therapy\\*\\*\n * 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\n\nNOTE: \\*\\*Preoperative endocrine therapy with a duration of \\< 30 days is not considered prior neoadjuvant therapy\n\n* No evidence of recurrent or metastatic disease\n* No history of breast cancer, except ductal carcinoma in situ or lobular carcinoma in situ\n* Hormone receptor status:\n\n * Not specified\n\nPATIENT CHARACTERISTICS:\n\nAge\n\n* 18 and over\n\nSex\n\n* Female\n\nMenopausal status\n\n* Premenopausal or postmenopausal\n\nPerformance status\n\n* Karnofsky 80-100% OR\n* ECOG 0-1\n\nLife expectancy\n\n* Not specified\n\nHematopoietic\n\n* Not specified\n\nHepatic\n\n* Not specified\n\nRenal\n\n* Creatinine ≤ 1.5 times upper limit of normal\n\nOther\n\n* Not pregnant or nursing\n* Fertile patients must use effective contraception\n* No active dental problems, including dental abscess or infection of the jaw bone (e.g., maxilla or mandible)\n* No prior or current diagnosis of osteonecrosis of the jaw\n* 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\n* No history of disease with influence on bone metabolism, including any of the following:\n\n * Paget's disease of the bone\n * Primary hyperparathyroidism\n * Osteoporosis requiring treatment or likely to require treatment within the next 6 months\n* No other severe physical or psychological disease that would preclude study compliance\n* No known hypersensitivity to bisphosphonates\n\nPRIOR CONCURRENT THERAPY:\n\nChemotherapy\n\n* See Disease Characteristics\n\nEndocrine therapy\n\n* See Disease Characteristics\n\nRadiotherapy\n\n* See Disease Characteristics\n\nSurgery\n\n* See Disease Characteristics\n* More than 4 weeks since prior and no concurrent dental or jaw surgery (e.g., extractions or implants)\n\n * Dental fillings, teeth scaling and polishing, or minor gingival surgery within the past 4 weeks are allowed\n\nOther\n\n* More than 1 year since prior bisphosphonates\n* More than 30 days since prior investigational drugs\n* No concurrent investigational drugs (i.e., not locally approved for any indication)"}, 'identificationModule': {'nctId': 'NCT00072020', 'briefTitle': 'Chemotherapy and/or Hormone Therapy With or Without Zoledronate in Treating Women With Stage II or Stage III Breast Cancer', 'organization': {'class': 'NIH', 'fullName': 'National Cancer Institute (NCI)'}, 'officialTitle': 'Does Adjuvant Zoledronic Acid Reduce Recurrence in Patients With High Risk Localized Breast Cancer?', 'orgStudyIdInfo': {'id': 'SHEFF-AZURE'}, 'secondaryIdInfos': [{'id': 'CDR0000335111', 'type': 'REGISTRY', 'domain': 'PDQ (Physician Data Query)'}, {'id': 'EU-20315'}, {'id': 'ISRCTN79831382'}, {'id': 'BIG-1-04'}]}, 'armsInterventionsModule': {'interventions': [{'name': 'zoledronic acid', 'type': 'DRUG'}, {'name': 'adjuvant therapy', 'type': 'PROCEDURE'}, {'name': 'neoadjuvant therapy', 'type': 'PROCEDURE'}]}, 'contactsLocationsModule': {'overallOfficials': [{'name': 'Robert E. Coleman, MD, FRCP', 'affiliation': 'Cancer Research Centre at Weston Park Hospital'}, {'name': 'Victoria Hiley', 'affiliation': 'University of Leeds'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Sheffield', 'class': 'OTHER'}}}}