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Trial record 1 of 5 for:    Phase III Trial of Biphosphonates as Adjuvant Therapy for Primary Breast Cancer
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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
  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
NSABP Foundation Inc
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: August 19, 2014
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
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Clodronic Acid
Ibandronic acid
Zoledronic acid
Bone Density Conservation Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 20, 2014