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

Sponsor:	University of Sheffield
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00072020

Purpose

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.

Condition	Intervention	Phase
Breast Cancer Metastatic Cancer	Drug: zoledronic acid Procedure: adjuvant therapy Procedure: neoadjuvant therapy	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control
Official Title:	Does Adjuvant Zoledronic Acid Reduce Recurrence in Patients With High Risk Localized Breast Cancer?

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Zoledronic acid

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Disease-free survival as assessed annually for 10 years [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time to bone metastases as first recurrence assessed annually for 10 years [ Designated as safety issue: No ]
Time to bone metastases per se as assessed annually for 10 years [ Designated as safety issue: No ]
Time to distant metastases as assessed annually for 10 years [ Designated as safety issue: No ]
Overall survival as assessed by final analysis at 10 years [ Designated as safety issue: No ]
Skeletal-related events prior to development of bone metastases as assessed annually for 10 years [ Designated as safety issue: No ]
Skeletal-related events following development of bone metastases as assessed annually for 10 years [ Designated as safety issue: No ]
Safety and toxicity of zoledronic acid as assessed annually for 10 years [ Designated as safety issue: Yes ]
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 [ Designated as safety issue: No ]
Analysis of tumor-specific mutations, proteomics and gene expression changes in tumor cells [ Designated as safety issue: No ]

Study Start Date:

August 2003

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00072020

Sponsors and Collaborators

University of Sheffield

Investigators

Investigator:	Robert E. Coleman, MD, FRCP	Cancer Research Centre at Weston Park Hospital
Investigator:	Victoria Hiley	University of Leeds

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

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.

Study ID Numbers:	CDR0000335111, SHEFF-AZURE, EU-20315, ISRCTN79831382, BIG-1-04
Study First Received:	November 4, 2003
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00072020 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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

Additional relevant MeSH terms:

Zoledronic acid
Skin Diseases
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic
Breast Neoplasms
Bone Density Conservation Agents

Pharmacologic Actions
Neoplasms
Neoplastic Processes
Neoplasms by Site
Pathologic Processes
Neoplasm Metastasis
Breast Diseases

ClinicalTrials.gov processed this record on November 09, 2009