Overview

This trial is active, not recruiting.

Condition breast cancer
Treatments clodronate disodium, ibandronate sodium, zoledronic acid
Phase phase 3
Sponsor Southwest Oncology Group
Collaborator National Cancer Institute (NCI)
Start date July 2005
End date August 2016
Trial size 5400 participants
Trial identifier NCT00127205, CDR0000437061, S0307, U10CA032102

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Patients receive zoledronate IV over 15 minutes once a month for 6 months and then once every 3 months for 2.5 years.
zoledronic acid
Given IV
(Active Comparator)
Patients receive oral clodronate once daily for 35 months.
clodronate disodium
Given orally
(Experimental)
Patients receive oral ibandronate once daily for 35 months.
ibandronate sodium
Given orally

Primary Outcomes

Measure
Histologic confirmation of disease recurrence
time frame: scans or biopsy at recurrence
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
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
Overall survival
time frame: follow up completed every 6 months for 5 years and then annually for 5 years or until death
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

Secondary Outcomes

Measure
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

Eligibility Criteria

Female participants at least 18 years old.

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

Additional Information

Official title Phase III Trial of Bisphosphonates as Adjuvant Therapy for Primary Breast Cancer
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.
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by Southwest Oncology Group.