S0307 Phase III Trial of Bisphosphonates as Adjuvant Therapy for Primary Breast Cancer.
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|ClinicalTrials.gov Identifier: NCT00127205|
Recruitment Status : Active, not recruiting
First Posted : August 5, 2005
Results First Posted : August 28, 2019
Last Update Posted : August 28, 2020
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 or disease||Intervention/treatment||Phase|
|Breast Cancer||Drug: clodronate disodium Drug: ibandronate sodium Drug: zoledronic acid||Phase 3|
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||6097 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase III Trial of Bisphosphonates as Adjuvant Therapy for Primary Breast Cancer|
|Study Start Date :||July 2005|
|Actual Primary Completion Date :||December 2017|
|Estimated Study Completion Date :||January 2021|
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
Active Comparator: Arm II
Patients receive oral clodronate once daily for 35 months.
Drug: clodronate disodium
Experimental: Arm III
Patients receive oral ibandronate once daily for 35 months.
Drug: ibandronate sodium
- 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 ]Time from date of registration to date of first observation of recurrence or death due to any cause. Patients last known to be alive who have not experienced recurrence of disease are censored at their last contact date. The outcome for the disease-free survival will be presented as 5 year survival rate.
- Overall Survival [ Time Frame: follow up completed every 6 months for 5 years and then annually for 5 years or until death ]Time from date of registration to date of death due to any cause. Patients last known to be alive are censored at their last contact date. The outcome for overall survival will be presented as 5 year overall survival rate.
- Distributions of Sites of First Recurrence on the Three Arms. [ Time Frame: Disease assessments are completed every 6 months for 5 years then annually for 5 years or until death or recurrence ]All sites of invasive disease documented within 30 days of first documentation of invasive recurrence.
- Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs [ Time Frame: Toxicity assessment is repeated every 2 months for the first 6 months, then every 3 months until 3 years or end of treatment. ]Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00127205
|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||Toronto Sunnybrook Regional Cancer Centre|