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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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
Sponsor:
Collaborators:
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
Information provided by (Responsible Party):
Southwest Oncology Group

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.


Condition or disease Intervention/treatment Phase
Breast Cancer Drug: clodronate disodium Drug: ibandronate sodium Drug: zoledronic acid Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6097 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes 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

Information from the National Library of Medicine

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


Sponsors and Collaborators
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
Investigators
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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
  Study Documents (Full-Text)

Documents provided by Southwest Oncology Group:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00127205    
Other Study ID Numbers: CDR0000437061
S0307 ( Other Identifier: SWOG )
First Posted: August 5, 2005    Key Record Dates
Results First Posted: August 28, 2019
Last Update Posted: August 28, 2020
Last Verified: August 2020
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:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Zoledronic Acid
Ibandronic Acid
Clodronic Acid
Bone Density Conservation Agents
Physiological Effects of Drugs