Zoledronate, Clodronate, or Ibandronate in Treating Women Who Have Undergone Surgery for Stage I, Stage II, or Stage III Breast Cancer - Full Text View

Sponsor:	Southwest Oncology Group
Collaborators:	National Cancer Institute (NCI) North Central Cancer Treatment Group Eastern Cooperative Oncology Group National Surgical Adjuvant Breast and Bowel Project (NSABP) Cancer and Leukemia Group B NCIC Clinical Trials Group
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00127205

Purpose

RATIONALE: Zoledronate, clodronate, or ibandronate may delay or prevent bone metastases in patients with nonmetastatic breast cancer. It is not yet known whether zoledronate is more effective than clodronate or ibandronate in treating breast cancer.

PURPOSE: This randomized phase III trial is studying zoledronate to see how well it works compared to clodronate or ibandronate in treating women who have undergone surgery for stage I, stage II, or stage III breast cancer.

Condition	Intervention	Phase
Breast Cancer	Drug: clodronate disodium Drug: ibandronate sodium Drug: zoledronic acid	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Primary Purpose: Treatment
Official Title:	Phase III Trial of Bisphosphonates as Adjuvant Therapy for Primary Breast Cancer

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Ibandronic acid Zoledronic acid Ibandronate sodium

U.S. FDA Resources

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

Primary Outcome Measures:

Histologic confirmation of disease recurrence [ Designated as safety issue: No ]
Sites of first disease recurrence [ Designated as safety issue: No ]
Disease-free survival [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Zubrod performance status [ Designated as safety issue: No ]

Secondary Outcome Measures:

Correlation of inherited germ-line single nucleotide polymorphisms (SNP, rs2297480) in farnesyl diphosphate synthase (FDPS) with adverse event of acute phase reactions [ Designated as safety issue: No ]

Estimated Enrollment:	5400
Study Start Date:	July 2005
Estimated Primary Completion Date:	February 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm I Patients receive zoledronate IV over 15 minutes once a month for 6 months and then once every 3 months for 2.5 years.	Drug: zoledronic acid Given IV
Active Comparator: Arm II Patients receive oral clodronate once daily for 35 months.	Drug: clodronate disodium Given orally
Experimental: Arm III Patients receive oral ibandronate once daily for 35 months.	Drug: ibandronate sodium Given orally

Detailed Description:

OBJECTIVES:

Compare disease-free survival and overall survival of women with resected primary stage I-III adenocarcinoma of the breast treated with adjuvant zoledronate vs clodronate vs ibandronate.
Compare the distributions of sites of first disease recurrence in patients treated with these drugs.
Compare adverse events in patients treated with these drugs.
Correlate parathyroid hormone related protein status and N-telopeptide levels at baseline with disease-free survival and sites of first recurrence in patients treated with these drugs.
Investigate whether there is an association between inherited germ-line single nucleotide polymorphisms (SNP, rs2297480) in farnesyl diphosphate synthase (FDPS) and the adverse event of acute phase reactions in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 3 treatment arms.

Arm I: Patients receive zoledronate IV over 15 minutes once a month for 6 months and then once every 3 months for 2.5 years.
Arm II: Patients receive oral clodronate once daily for 35 months.
Arm III: Patients receive oral ibandronate once daily for 35 months. Treatment in all arms continues in the absence of disease recurrence or unacceptable toxicity.

After completion of study treatment, patients are followed every 6 months until disease recurrence and then annually for up to 10 years.

PROJECTED ACCRUAL: A total of 5,400 will be accrued for this study.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed primary adenocarcinoma of the breast
- Stage I-III disease
- No evidence of metastatic disease
Must have undergone lumpectomy or total mastectomy for primary disease within the past 12 weeks, or have completed chemotherapy within the past 8 weeks
- Axillary evaluation per institutional standards
Currently receiving or planning to receive standard adjuvant systemic therapy comprising chemotherapy, hormonal therapy, or combined chemotherapy/hormonal therapy for breast cancer
- Patients who are at low risk for disease recurrence and for whom adjuvant systemic therapy will not be prescribed are not eligible
- Patients who receive biologic agents only or local radiotherapy only (without chemotherapy and/or hormone therapy) are not eligible
- Additional therapies are allowed including radiotherapy and biologic agents (e.g., trastuzumab [Herceptin^®], bevacizumab, or hematopoietic growth factors)
- Neoadjuvant therapy or hormonal therapy alone is allowed provided study entry occurs ≥ 12 weeks after completion of surgery
Patients with skeletal pain are eligible provided bone scan and/or roentgenological exam are negative for metastatic disease
- Suspicious findings must be confirmed as benign by x-ray, MRI, or biopsy
Hormone receptor status:
- Not specified

PATIENT CHARACTERISTICS:

Age

18 and over

Sex

Female

Menopausal status

Not specified

Performance status

Zubrod 0-2

Life expectancy

Not specified

Hematopoietic

Not specified

Hepatic

Not specified

Renal

Creatinine ≤ 2 times upper limit of normal
Creatinine clearance ≥ 30 mL/min
No renal failure

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No history of esophageal stricture or motility disorders
- Gastroesophageal reflux disorder allowed
No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

Prior or concurrent hematopoietic growth factors allowed
HER-2-targeted therapies allowed
Antiangiogenics allowed

Chemotherapy

See Disease Characteristics

Endocrine therapy

See Disease Characteristics

Radiotherapy

Concurrent radiotherapy to the breast, chest wall, or lymph node group allowed at the discretion of the treating physician

Surgery

See Disease Characteristics

Other

Prior neoadjuvant therapy allowed
Prior bisphosphonates for bone density allowed
No other concurrent bisphosphonates as adjuvant therapy or for treatment of osteoporosis
No concurrent enrollment in clinical trials with bone density as an endpoint
- Concurrent enrollment on any other locoregional or systemic therapy breast cancer study (including cooperative group studies) allowed

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00127205

Sponsors and Collaborators

Southwest Oncology Group

National Cancer Institute (NCI)

North Central Cancer Treatment Group

Eastern Cooperative Oncology Group

National Surgical Adjuvant Breast and Bowel Project (NSABP)

Cancer and Leukemia Group B

NCIC Clinical Trials Group

Investigators

Investigator:	Julie R. Gralow, MD	Seattle Cancer Care Alliance
Investigator:	Robert B. Livingston, MD	University of Arizona
Investigator:	James N. Ingle, MD	Mayo Clinic
Investigator:	Carla I. Falkson, MD	University of Alabama at Birmingham
Investigator:	Alexander H. G. Paterson, MD, FRCP, FACP, MBChB	Tom Baker Cancer Centre - Calgary
Investigator:	Elizabeth C. Dees, MD	UNC Lineberger Comprehensive Cancer Center
Investigator:	Mark J. Clemons, MD	Odette Cancer Centre at Sunnybrook

More Information

Additional Information:

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

Featured trial article This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Laurence H. Baker, Southwest Oncology Group - Group Chair's Office
ClinicalTrials.gov Identifier:	NCT00127205 History of Changes
Other Study ID Numbers:	CDR0000437061, SWOG-S0307, NCCTG-SWOG-S0307, ECOG-SWOG-S0307, NSABP-SWOG-S0307, CALGB-SWOG-S0307, CAN-NCIC-SWOG-S0307
Study First Received:	August 3, 2005
Last Updated:	May 19, 2012
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Zoledronic acid

Ibandronic acid
Clodronic Acid
Diphosphonates
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 21, 2012