S0307 Zoledronate, Clodronate, or Ibandronate in Treating Women Who Have Undergone Surgery for Stage I, Stage II, or Stage III Breast Cancer
This study is ongoing, but not recruiting participants.
Sponsor:
Southwest Oncology Group
Collaborators:
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 (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00127205
First received: August 3, 2005
Last updated: May 22, 2013
Last verified: May 2013
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
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 Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Phase III Trial of Bisphosphonates as Adjuvant Therapy for Primary Breast Cancer |
Resource links provided by NLM:
Further study details as provided by Southwest Oncology Group:
Primary Outcome Measures:
- Histologic confirmation of disease recurrence [ Time Frame: scans or biopsy at recurrence ] [ Designated as safety issue: No ]
- Sites of first disease recurrence [ Time Frame: Disease assessments are completed every 6 months for 5 years then annually for 5 years or until death or recurrence ] [ Designated as safety issue: No ]
- Disease-free survival [ Time Frame: Disease assessments are completed every 6 months for 5 years then annually for 5 years or until death or recurrence ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: follow up completed every 6 months for 5 years and then annually for 5 years or until death ] [ Designated as safety issue: No ]
- Zubrod performance status [ Time Frame: Assessed every 8 weeks for 6 months then every 3 months while on treatment, then every 6 months for 5 years then annually for 5 years or until death ] [ 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 [ Time Frame: collected at baseline ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 5400 |
| Study Start Date: | July 2005 |
| Estimated Study Completion Date: | May 2020 |
| 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
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
| Study Chair: | Julie R. Gralow, MD | Seattle Cancer Care Alliance |
| Study Chair: | Robert B. Livingston, MD | University of Arizona |
| Study Chair: | James N. Ingle, MD | Mayo Clinic |
| Study Chair: | Carla I. Falkson, MD | University of Alabama at Birmingham |
| Study Chair: | Alexander H Paterson, MD, FRCP | Tom Baker Cancer Centre - Calgary |
| Study Chair: | Elizabeth C. Dees, MD | UNC Lineberger Comprehensive Cancer Center |
| Study Chair: | Mark J. Clemons, MD | Odette Cancer Centre at Sunnybrook |
More Information
Additional Information:
No publications provided
| Responsible Party: | Southwest Oncology Group |
| ClinicalTrials.gov Identifier: | NCT00127205 History of Changes |
| Other Study ID Numbers: | CDR0000437061, S0307, U10CA032102 |
| Study First Received: | August 3, 2005 |
| Last Updated: | May 22, 2013 |
| Health Authority: | United States: Federal Government United States: Food and Drug Administration |
Keywords provided by Southwest Oncology Group:
|
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 22, 2013