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Clodronate With or Without Chemotherapy and/or Hormonal Therapy in Treating Women With Stage I or Stage II Breast Cancer

Phase 3
Completed
Conditions
Breast Cancer
Interventions
Drug: placebo
Registration Number
NCT00009945
Lead Sponsor
NSABP Foundation Inc
Brief Summary

RATIONALE: Clodronate may be effective in preventing the spread of cancer to the bones and other parts of the body. It is not yet known whether clodronate is more effective alone or combined with chemotherapy and /or hormonal therapy in preventing metastatic breast cancer.

PURPOSE: Randomized phase III trial to determine the effectiveness of clodronate with or without chemotherapy and /or hormonal therapy in preventing metastases in women who have stage I or stage II breast cancer.

Detailed Description

OBJECTIVES:

* Determine whether clodronate administered alone or in addition to adjuvant chemotherapy and/or hormonal therapy improves disease-free survival in women with early stage breast cancer.

* Determine whether clodronate reduces the incidence of skeletal metastases and non-skeletal metastases in these patients.

* Determine whether clodronate improves overall and relapse-free survival in these patients.

* Determine whether clodronate reduces the incidence of skeletal morbidity (e.g., skeletal fractures, hypercalcemia, skeletal pain, need for radiotherapy, spinal cord compression) in these patients.

* Investigate the relevance of serum markers of bone turnover as a prognostic factor for the development of bone metastasis in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified by age (under 50 vs 50 and over), number of positive lymph nodes (0 vs 1-3 vs 4 or more), and hormone receptor status (estrogen receptor \[ER\] and progesterone receptor \[PR\] negative vs ER and/or PR positive). Patients are randomized to one of two treatment arms.

Patients in both arms commence treatment within 2 weeks of randomization and continue treatment for 3 years in the absence of bone metastasis or unacceptable toxicity. Study medication must be continued in the case of documented visceral or soft tissue metastasis or other event without skeletal metastasis.

Patients in both arms may also receive adjuvant chemotherapy and/or tamoxifen at the discretion of the protocol investigator. Patients receiving hormonal therapy begin hormonal therapy within 3-12 weeks after the last dose of chemotherapy and continue for a minimum of 5 years.

Patients who have undergone a prior lumpectomy receive adjuvant whole breast radiotherapy. Patients who have undergone a prior mastectomy may receive radiotherapy at the investigator's discretion.

Patients are followed every 6 months for 5 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 3,323 patients will be accrued for this study within 3.5 years.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
3323
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm 1: ClodronateclodronatePatient receives 2 tablets once daily for 3 years.
Arm 2: PlaceboplaceboPatient receives 2 tablets once daily for 3 years.
Primary Outcome Measures
NameTimeMethod
Disease Free Survival.8 years

Time to first event where an event is any recurrences, 2nd primary or death to determine the percentage of patients disease free at 8 years

Secondary Outcome Measures
NameTimeMethod
Skeletal Metastasis Free Survival8 years

Time from randomization to first diagnosis of skeletal metastasis to determine the percentage of patient free of skeletal metastasis at 8 years

Overall Survival8 years

Time from randomization to any death to determine the percentage of patients alive at 8 years

Relapse Free Survival8 years

Time from randomization to any local, regional, or distant recurrence of breast cancer to determine the percentage of patients relapse free at 8 years

Incidence of Non-skeletal Metastasis8 years

Time from randomization to incidence of non-skeletal metastasis to determine the percentage of patients free from non-skeletal metastasis at 8 years

Trial Locations

Locations (17)

Altru Cancer Center

🇺🇸

Grand Forks, North Dakota, United States

Fletcher Allen Health Care - University Health Center Campus

🇺🇸

Burlington, Vermont, United States

CCOP - Mayo Clinic Scottsdale Oncology Program

🇺🇸

Scottsdale, Arizona, United States

Veterans Affairs Medical Center - Biloxi

🇺🇸

Biloxi, Mississippi, United States

Siouxland Hematology-Oncology

🇺🇸

Sioux City, Iowa, United States

Medcenter One Health System

🇺🇸

Bismarck, North Dakota, United States

CCOP - Geisinger Clinic and Medical Center

🇺🇸

Danville, Pennsylvania, United States

Rapid City Regional Hospital

🇺🇸

Rapid City, South Dakota, United States

University of Tennessee Cancer Institute

🇺🇸

Memphis, Tennessee, United States

Danville Radiation Therapy Center

🇺🇸

Memphis, Tennessee, United States

Harrington Cancer Center

🇺🇸

Amarillo, Texas, United States

Veterans Affairs Medical Center - Amarillo

🇺🇸

Amarillo, Texas, United States

CCOP - Cedar Rapids Oncology Project

🇺🇸

Cedar Rapids, Iowa, United States

University of Washington School of Medicine

🇺🇸

Seattle, Washington, United States

MBCCOP - Hawaii

🇺🇸

Honolulu, Hawaii, United States

MBCCOP - Massey Cancer Center

🇺🇸

Richmond, Virginia, United States

Mayo Clinic

🇺🇸

Jacksonville, Florida, United States

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