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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:
Collaborators:
North Central Cancer Treatment Group
Eastern Cooperative Oncology Group
NSABP Foundation Inc
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: August 19, 2014
Last verified: August 2014

August 3, 2005
August 19, 2014
July 2005
February 2015   (final data collection date for primary outcome measure)
  • 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 ]
Not Provided
Complete list of historical versions of study NCT00127205 on ClinicalTrials.gov Archive Site
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 ]
Not Provided
Not Provided
Not Provided
 
S0307 Zoledronate, Clodronate, or Ibandronate in Treating Women Who Have Undergone Surgery for Stage I, Stage II, or Stage III Breast Cancer
Phase III Trial of Bisphosphonates as Adjuvant Therapy for Primary Breast Cancer

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.

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.

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Breast Cancer
  • Drug: clodronate disodium
    Given orally
  • Drug: ibandronate sodium
    Given orally
  • Drug: zoledronic acid
    Given IV
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
5400
May 2020
February 2015   (final data collection date for primary outcome measure)

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
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT00127205
CDR0000437061, S0307, U10CA032102
Yes
Southwest Oncology Group
Southwest Oncology Group
  • 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
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
Southwest Oncology Group
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP