Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Risedronate in Preventing Bone Loss in Premenopausal Women Receiving Chemotherapy for Primary Breast Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Supportive care Closed 18 and over NCI NCCTG-N02C1 N02C1, NCT00054418

Objectives

1. Compare the effectiveness of risedronate vs placebo in the prevention of bone loss in premenopausal women undergoing adjuvant or neoadjuvant chemotherapy for primary breast cancer.
2. Compare the degree of bone loss over 1 year in these women according to menopausal status after 1 year of therapy.
3. Determine the relationship of current climacteric symptoms, menstrual and reproductive history, and chemotherapy regimen with ovarian failure (permanent cessation of menses) in these women.
4. Determine the relationship of baseline serum estradiol levels with ovarian failure in these women.

Entry Criteria

Disease Characteristics:

• Resectable primary breast cancer
  • Stage I-IIIB disease



• Scheduled to undergo adjuvant or neoadjuvant chemotherapy



• No hypercalcemia (calcium level greater than 1 mg/dL above upper limit of normal within the past 6 months)



• No hypocalcemia (calcium level greater than 0.5 mg/dL below lower limit of normal within the past 6 months)



• No diseases affecting bone metabolism (i.e., hyperparathyroidism, hyperthyroidism, and hypercortisolism)



• Bone mineral density T score of -2.0 or greater at the hip or spine (T score of -2.1 or less is ineligible)

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• No concurrent estrogen
• No concurrent estrogen receptor modulators except tamoxifen
• No corticosteroid dose of prednisone or equivalent greater than 5 mg daily for more than 2 weeks within the past 6 months
• No concurrent estrogen replacement therapy
• No concurrent oral contraceptives

Radiotherapy

• Not specified

Surgery

• More than 3 months since prior and no concurrent dental extraction, root canal, or dental implants
• No prior bilateral oophorectomy

Other

• No prior bisphosphonates
• No other concurrent bisphosphonates

Patient Characteristics:

Age

• 18 and over

Sex

• Female

Menopausal status

• Premenopausal meeting the following criteria:
  • No more than 6 months since last menstrual period
  • No prior bilateral oophorectomy
  • Not on estrogen replacement therapy
    • If total abdominal hysterectomy performed, then must have at least 1 intact ovary
    • If more than 3 months since last menstrual period, then must have premenopausal estrogen levels within 1 month of study entry

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Creatinine no greater than 2.0 mg/dL
• No history of severe renal impairment

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception
• Able to stand or sit upright for at least 30 minutes
• No known swallowing disorder
• No history of vertebral compression fracture
  • Traumatic fracture of the coccyx allowed
• No malabsorption syndrome

Expected Enrollment

A total of 220 patients (110 per treatment arm) will be accrued for this study within 11 months.

Outcomes

Average intra-patient change in lumbar spine (L2-L4, PA) bone mineral density (BMD) from baseline to one year after study entry

Average intra-patient change in femoral neck and total hip BMD from baseline to one year after study entry
Incidence of osteopenia in the risedronate vs placebo groups at one year after study entry
Incidence of osteoporosis in the risedronate vs placebo groups at one year after study entry
Incidence of a 5% difference in intra-patient BMD scores at baseline
Serum and urine N-telopeptide and serum alkaline phosphatase at baseline and 6 months
Frequency and severity of toxicity as measured by NCI CTC version 2.0
Menopausal symptoms as measured by the Greene Climacteric Scale (GCS) at baseline, monthly during chemotherapy, at 6 months, 1 year, and 2 years after study entry
Association of baseline serum estradiol levels with permanent cessation of menses
Relationship between the subscales of the GCS (psychological, vasomotor, somatic and sexual) with type of chemotherapy, duration of chemotherapy, and menstrual cycle changes

Outline

This is a randomized, placebo-controlled, double-blind study. Patients are stratified according to planned tamoxifen therapy (yes vs no vs undecided), planned taxane therapy (yes vs no vs undecided), time from last menses (1-3 months vs longer than 3 months to 6 months), and age (under 40 vs 40 to 49 vs 50 and over). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral calcium and oral cholecalciferol daily and oral risedronate once weekly.



• Arm II: Patients receive calcium and cholecalciferol as in arm I and oral placebo once weekly.

In both arms, treatment begins during the first month of chemotherapy and continues for 1 year in the absence of unacceptable toxicity.

Questionnaires about cessation of menses, ovarian failure, and menopausal symptoms are completed at baseline, monthly during chemotherapy, at 6 months, and then at 1 and 2 years.

Patients are followed for 1 year.

Trial Contact Information

Trial Lead Organizations

North Central Cancer Treatment Group

Stephanie Hines, MD, Protocol chair		Ph: 904-953-0707

Registry Information
Official Title		A Phase III Randomized, Placebo-Controlled, Double-Blind Trial Of Risedronate (Actonel) For Prevention Of Bone Loss In Premenopausal Women Undergoing Chemotherapy For Primary Breast Carcinoma
Trial Start Date		2003-03-21
Registered in ClinicalTrials.gov		NCT00054418
Date Submitted to PDQ		2002-12-31
Information Last Verified		2006-05-21
NCI Grant/Contract Number		CA25224

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