S0307 Phase III Trial of Bisphosphonates as Adjuvant Therapy for Primary Breast Cancer.

Tracking Information
First Submitted Date ICMJE	August 3, 2005
First Posted Date ICMJE	August 5, 2005
Last Update Posted Date	December 15, 2017
Study Start Date ICMJE	July 2005
Actual Primary Completion Date	December 2017 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: May 22, 2013)	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 ]
Original Primary Outcome Measures ICMJE	Not Provided
Change History	Complete list of historical versions of study NCT00127205 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: May 22, 2013)	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 ]
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	S0307 Phase III Trial of Bisphosphonates as Adjuvant Therapy for Primary Breast Cancer.
Official Title ICMJE	Phase III Trial of Bisphosphonates as Adjuvant Therapy for Primary Breast Cancer
Brief 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.
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.
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Breast Cancer
Intervention ICMJE	Drug: clodronate disodium Given orally; Drug: ibandronate sodium Given orally; Drug: zoledronic acid Given IV
Study Arms	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. Intervention: Drug: zoledronic acid; Active Comparator: Arm II Patients receive oral clodronate once daily for 35 months. Intervention: Drug: clodronate disodium; Experimental: Arm III Patients receive oral ibandronate once daily for 35 months. Intervention: Drug: ibandronate sodium
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Active, not recruiting
Estimated Enrollment ICMJE; (submitted: September 10, 2009)	5400
Original Enrollment ICMJE	Not Provided
Estimated Study Completion Date	May 2020
Actual Primary Completion Date	December 2017 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: Female
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Not Provided
Removed Location Countries	Canada, United States
Administrative Information
NCT Number ICMJE	NCT00127205
Other Study ID Numbers ICMJE	CDR0000437061; S0307 ( Other Identifier: SWOG ); U10CA032102 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Southwest Oncology Group
Study Sponsor ICMJE	Southwest Oncology Group
Collaborators ICMJE	National Cancer Institute (NCI); North Central Cancer Treatment Group; Eastern Cooperative Oncology Group; NSABP Foundation Inc; Cancer and Leukemia Group B; NCIC Clinical Trials Group
Investigators ICMJE	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
PRS Account	Southwest Oncology Group
Verification Date	December 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP