Conditions: Breast Cancer
Keywords: stage I breast cancer stage II breast cancer
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 3323
Healthy volunteers: no

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.

Arms:
arm 1: Patient receives 2 tablets once daily for 3 years. arm 2: Patient receives 2 tablets once daily for 3 years.

Interventions: intervention 1: clodronate intervention 2: placebo
Intervention descriptions: intervention 1: 1600 mg PO daily intervention 2: 2 pills PO daily

Protocol document: