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Breast CancerPhase 3NCT00127205

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

A Phase 3 study testing clodronate disodium, ibandronate sodium and zoledronic acid in people with Breast Cancer, run by SWOG Cancer Research Network.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
clodronate disodium, ibandronate sodium and zoledronic acid
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6,097 participants
Where
No sites listed yet
Study dates
Jul 2005to 29 Mar 2021
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

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

About this study

Official title: 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.

Read the 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.

Conditions
Breast Cancer
Being tested
clodronate disodium, ibandronate sodium, zoledronic acid
Keywords
stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • clodronate disodiumDrug

    Given orally

  • ibandronate sodiumDrug

    Given orally

  • zoledronic acidDrug

    Given IV

Study groups in NCT00127205
Study groupRoleWhat they receive
Arm IExperimentalPatients receive zoledronate IV over 15 minutes once a month for 6 months and then once every 3 months for 2.5 years.
Receives: Drug: zoledronic acid
Arm IIActive comparatorPatients receive oral clodronate once daily for 35 months.
Receives: Drug: clodronate disodium
Arm IIIExperimentalPatients receive oral ibandronate once daily for 35 months.
Receives: Drug: ibandronate sodium

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Disease-free Survival

    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.

    Measured: Disease assessments are completed every 6 months for 5 years then annually for 5 years or until death or recurrence

Secondary outcomes (3)

  1. Overall Survival

    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.

    Measured: follow up completed every 6 months for 5 years and then annually for 5 years or until death

  2. Distributions of Sites of First Recurrence on the Three Arms.

    All sites of invasive disease documented within 30 days of first documentation of invasive recurrence.

    Measured: Disease assessments are completed every 6 months for 5 years then annually for 5 years or until death or recurrence

  3. Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs

    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.

    Measured: Toxicity assessment is repeated every 2 months for the first 6 months, then every 3 months until 3 years or end of treatment.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Aug 2005 (estimated)
  2. Study startJul 2005
  3. Primary completionDec 2017
  4. Study completion29 Mar 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
6,097 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00127205
Sponsor's protocol ID
CDR0000437061
Other IDs
S0307
Status last verified
Jun 2021
First submitted
3 Aug 2005
Last updated
2 Jul 2021
Data monitoring committee
Yes

Publications

  • Adams A, Jakob T, Huth A, Monsef I, Ernst M, Kopp M, Caro-Valenzuela J, Wockel A, Skoetz N. Bone-modifying agents for reducing bone loss in women with early and locally advanced breast cancer: a network meta-analysis. Cochrane Database Syst Rev. 2024 Jul 9;7(7):CD013451. doi: 10.1002/14651858.CD013451.pub2.

    PubMed 38979716

  • Kizub DA, Miao J, Schubert MM, Paterson AHG, Clemons M, Dees EC, Ingle JN, Falkson CI, Barlow WE, Hortobagyi GN, Gralow JR. Risk factors for bisphosphonate-associated osteonecrosis of the jaw in the prospective randomized trial of adjuvant bisphosphonates for early-stage breast cancer (SWOG 0307). Support Care Cancer. 2021 May;29(5):2509-2517. doi: 10.1007/s00520-020-05748-8. Epub 2020 Sep 15.

    PubMed 32929540

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing clodronate disodium, ibandronate sodium and zoledronic acid in people with Breast Cancer, run by SWOG Cancer Research Network.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00127205, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2021.

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