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

NCT00127205 | Completed Phase 3 Results DMC

• 2 other identifiers: CDR0000437061S0307
• Study Type: interventional
• Target: 6,097
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Breast Cancer

Keywords

stage I breast cancer; stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (3)

• Overall Survival

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

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

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

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

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

Study Arms (3)

Arm I

EXPERIMENTAL

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

Arm II

ACTIVE COMPARATOR

Patients receive oral clodronate once daily for 35 months.

Drug: clodronate disodium

Arm III

EXPERIMENTAL

Patients receive oral ibandronate once daily for 35 months.

Drug: ibandronate sodium

Interventions

clodronate disodium DRUG

Given orally

Arm II

ibandronate sodium DRUG

Given orally

Arm III

zoledronic acid DRUG

Given IV

Arm I

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• SWOG Cancer Research Network: lead
• National Cancer Institute (NCI): collaborator
• North Central Cancer Treatment Group: collaborator
• Eastern Cooperative Oncology Group: collaborator
• NSABP Foundation Inc: collaborator
• Cancer and Leukemia Group B: collaborator
• NCIC Clinical Trials Group: collaborator

Related Publications (2)

• 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.

  PMID: 38979716 DERIVED

• 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.

  PMID: 32929540 DERIVED

Related Links

• Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Clodronic Acid; Ibandronic Acid; Zoledronic Acid

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: SWOG statistician
• Organization: SWOG Statistics & Data Management Center

jmiao@fredhutch.org

2066674263

Study Officials

• 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 CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2005
• First Posted: August 5, 2005
• Study Start: July 1, 2005
• Primary Completion: December 1, 2017
• Study Completion: March 29, 2021
• Last Updated: July 2, 2021
• Results First Posted: August 28, 2019

Record last verified: 2021-06