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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00054418
• Other study ID #: NCCTG-N02C1
• Secondary ID: NCI-2012-02515CD
• Status: Completed
• Phase: Phase 3
• First received: February 5, 2003
• Last updated: July 12, 2016
• Start date: March 2003
• Est. completion date: May 2008

Study information

• Verified date: July 2016
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Preventing bone loss in patients who are receiving chemotherapy for breast cancer may decrease the risk of fractures and may help patients live more comfortably. It is not yet known whether calcium is more effective with or without risedronate in preventing bone loss.

PURPOSE: This randomized phase III trial is studying two forms of calcium with or without risedronate to compare how well they work in preventing bone loss in premenopausal women who are receiving chemotherapy for primary stage I, stage II, stage IIIA, or stage IIIB breast cancer.

Description:

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. In both arms, treatment begins during the first month of chemotherapy and continues for 1 year in the absence of unacceptable toxicity. For more information regarding the treatment arms, please see the "Arms" section below. 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. A summary of study goals is listed below.

Goals:

1. To evaluate the effectiveness of risedronate at a weekly oral dose of 35 mg versus placebo in the prevention of bone loss in premenopausal women undergoing adjuvant or neoadjuvant chemotherapy for primary breast cancer.

2. To evaluate the degree of bone loss over one year in premenopausal women undergoing adjuvant chemotherapy for primary breast cancer according to menopausal status at one year after therapy begins.

3. To evaluate the relationship of current climacteric symptoms, menstrual and reproductive history, and chemotherapy regimen with ovarian failure (permanent cessation of menses) in premenopausal women undergoing adjuvant or neoadjuvant chemotherapy for primary breast cancer.

4. To evaluate the relationship of baseline serum estradiol levels with ovarian failure in premenopausal women undergoing adjuvant or neoadjuvant chemotherapy for primary breast cancer.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 216
• Est. completion date: May 2008
• Est. primary completion date: April 2007
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

1. Required Characteristics

1. Premenopausal women

• = 6 months since last menstrual period

• no prior bilateral oophorectomy

• not on estrogen replacement therapy

• if TAH is performed, with at least one intact ovary, or if > 3 months since last menstrual period, then patients must have premenopausal estrogen levels = 1 month of study entry

2. Scheduled to undergo adjuvant or neoadjuvant chemotherapy for primary breast cancer (stages I-IIIB)

3. = 18 years of age

4. ECOG performance status (PS) 0 or 1

2. Contraindications

1. Hypercalcemia (calcium level > 1mg/dL above UNL = 6 months

2. Hypocalcemia (calcium level > 0.5 mg/dL below UNL = 6 months

3. Inability to stand or sit upright for at least 30 minutes

4. Known swallowing disorder

5. Bone mineral density T score of = - 2.0 at the hip or lumbar spine

• a patient with a T score of - 2.1 is ineligible

• a patient with a T score of - 1.9 is eligible

6. History of vertebral compression fracture

• Exception: traumatic fracture of the coccyx would not exclude a patient from participation

7. Corticosteroids at doses > 5 mg daily of prednison or equivalent for > 2 weeks in the past 6 months

8. Previous treatment with bisphosphonates

9. Diseases affecting bone metabolism (hyperthyroidism, hyperparathyroidism, and hypercortisolism)

10. History of severe renal impairment or creatinine > 2.0 mg/dL

11. Malabsorption syndrome

12. Estrogen replacement therapy

13. Oral contraceptive use

14. Prior bilateral oophorectomy

15. Pregnant women

• Nursing women

• Women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragm, injections, intrauterine device [IUD], surgical sterilization, abstinence, etc.)

• This study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown

16. Dental extraction, root canal, or implants = 3 months prior to registration or planned during study treatment

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Osteoporosis

Intervention

Dietary Supplement:
• calcium carbonate
calcium 600 mg daily administered orally for one year
• vitamin D
vitamin D 400 U daily administered orally for one year

Drug:
• risedronate sodium
risedronate 35 mg weekly administered orally

Other:
• placebo
placebo tablet weekly administered orally for one year

Locations

Country	Name	City	State
Canada	Allan Blair Cancer Centre at Pasqua Hospital	Regina	Saskatchewan
United States	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan
United States	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest	Allentown	Pennsylvania
United States	McFarland Clinic, P. C.	Ames	Iowa
United States	Rose Ramer Cancer Clinic at Anderson Area Medical Center	Anderson	South Carolina
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	St. Joseph Mercy Cancer Center at St. Joseph Mercy Hospital	Ann Arbor	Michigan
United States	CCOP - Atlanta Regional	Atlanta	Georgia
United States	Northside Hospital Cancer Center	Atlanta	Georgia
United States	Piedmont Hospital	Atlanta	Georgia
United States	Saint Joseph's Hospital of Atlanta	Atlanta	Georgia
United States	MBCCOP-Medical College of Georgia Cancer Center	Augusta	Georgia
United States	Aurora Presbyterian Hospital	Aurora	Colorado
United States	Rush-Copley Cancer Care Center	Aurora	Illinois
United States	WellStar Cobb Hospital	Austell	Georgia
United States	Ochsner Clinic of Baton Rouge	Baton Rouge	Louisiana
United States	MeritCare Clinic - Bemidji	Bemidji	Minnesota
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Deaconess Billings Clinic - Downtown	Billings	Montana
United States	Deaconess Billings Clinic Cancer Center	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	St. Vincent Healthcare	Billings	Montana
United States	Bismarck Cancer Center	Bismarck	North Dakota
United States	Cancer Care Center at Medcenter One Hospital	Bismarck	North Dakota
United States	Mid Dakota Clinic, P. C.	Bismarck	North Dakota
United States	St. Alexius Medical Center	Bismarck	North Dakota
United States	St. Joseph Medical Center	Bloomington	Illinois
United States	Boulder Community Hospital	Boulder	Colorado
United States	Wood County Oncology Center	Bowling Green	Ohio
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Internal Medicine Associates of Bozeman	Bozeman	Montana
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	St. James Community Hospital	Butte	Montana
United States	Graham Hospital	Canton	Illinois
United States	Saint Anthony Regional Hospital	Carroll	Iowa
United States	Memorial Hospital	Carthage	Illinois
United States	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa
United States	Mercy Regional Cancer Center at Mercy Medical Center	Cedar Rapids	Iowa
United States	St. Luke's Hospital	Cedar Rapids	Iowa
United States	Cancer Center of Kansas, P.A. - Chanute	Chanute	Kansas
United States	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	Alegent Health Mercy Hospital	Council Bluffs	Iowa
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Charles B. Eberhart Cancer Center at DeKalb Medical Center	Decatur	Georgia
United States	CCOP - Colorado Cancer Research Program, Incorporated	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - St. Luke's Medical Center	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	St. Joseph Hospital	Denver	Colorado
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa
United States	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mercy Capitol Hospital	Des Moines	Iowa
United States	Cancer Center of Kansas, P.A. - Dodge City	Dodge City	Kansas
United States	CCOP - Duluth	Duluth	Minnesota
United States	Miller-Dwan Medical Center	Duluth	Minnesota
United States	St. Mary's - Duluth Clinic Cancer Center	Duluth	Minnesota
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Cancer Center of Kansas, P.A. - El Dorado	El Dorado	Kansas
United States	Swedish Medical Center	Englewood	Colorado
United States	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan
United States	Eureka Community Hospital	Eureka	Illinois
United States	CCOP - MeritCare Hospital	Fargo	North Dakota
United States	MeritCare Medical Group	Fargo	North Dakota
United States	Blanchard Valley Medical Associates	Findlay	Ohio
United States	Fremont Memorial Hospital	Fremont	Ohio
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Galesburg Clinic	Galesburg	Illinois
United States	Galesburg Cottage Hospital	Galesburg	Illinois
United States	InterCommunity Cancer Center of Western Illinois	Galesburg	Illinois
United States	Altru Cancer Center at Altru Hospital	Grand Forks	North Dakota
United States	Great Falls Clinic	Great Falls	Montana
United States	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology, Limited at St. Vincent Hospital	Green Bay	Wisconsin
United States	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Hattiesburg Clinic, P.A.	Hattiesburg	Mississippi
United States	Mason District Hospital	Havana	Illinois
United States	St. Peter's Hospital	Helena	Montana
United States	Hopedale Medical Complex	Hopedale	Illinois
United States	Terrebonne General Medical Center	Houma	Louisiana
United States	Green Bay Oncology, Limited - Iron Mountain	Iron Mountain	Michigan
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	Joliet Oncology Hematology Associates, Limited - West	Joliet	Illinois
United States	Glacier Oncology, PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology	Kalispell	Montana
United States	Kenton Oncology, Incorporated	Kenton	Ohio
United States	Kewanee Hospital	Kewanee	Illinois
United States	Cancer Center of Kansas, P.A. - Kingman	Kingman	Kansas
United States	Haematology-Oncology Associates of Ohio and Michigan, P.C.	Lambertville	Michigan
United States	Gwinnett Medical Center	Lawrenceville	Georgia
United States	Southwest Medical Center	Liberal	Kansas
United States	Lima Memorial Hospital	Lima	Ohio
United States	Bryan LGH Medical Center West	Lincoln	Nebraska
United States	Cancer Resource Center - Lincoln	Lincoln	Nebraska
United States	St. Elizabeth Regional Medical Center	Lincoln	Nebraska
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Hope Cancer Care Center at Longmont United Hospital	Longmont	Colorado
United States	McDonough District Hospital	Macomb	Illinois
United States	Immanuel St. Joseph's Clinic	Mankato	Minnesota
United States	Kennestone Cancer Center at Wellstar Kennestone Hospital	Marietta	Georgia
United States	Northwest Ohio Oncology Center	Maumee	Ohio
United States	St. Luke's Hospital	Maumee	Ohio
United States	Saint Anthony Memorial Health Centers	Michigan City	Indiana
United States	Eastern Montana Cancer Center	Miles City	Montana
United States	Virginia Piper Cancer Institute at Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Community Medical Center	Missoula	Montana
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Alegent Health Community Memorial Hospital	Missouri Valley	Iowa
United States	Mobile Infirmary Medical Center	Mobile	Alabama
United States	Trinity Medical Center - East	Moline	Illinois
United States	Community Cancer Center of Monroe	Monroe	Michigan
United States	Mercy Memorial Hospital System	Monroe	Michigan
United States	CCOP - Ochsner	New Orleans	Louisiana
United States	Ochsner Cancer Institute at Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Cancer Center of Kansas, P.A. - Newton	Newton	Kansas
United States	BroMenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center	Normal	Illinois
United States	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin
United States	Bergan Mercy Medical Center	Omaha	Nebraska
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Immanuel Medical Center	Omaha	Nebraska
United States	Burgess Health Center	Onawa	Iowa
United States	St. Charles Mercy Hospital	Oregon	Ohio
United States	Toledo Clinic - Oregon	Oregon	Ohio
United States	Community Hospital of Ottawa	Ottawa	Illinois
United States	Oncology Hematology Associates of Central Illinois - Ottawa	Ottawa	Illinois
United States	Ottumwa Regional Health Center Cancer Center	Ottumwa	Iowa
United States	Midlands Cancer Center at Midlands Community Hospital	Papillion	Nebraska
United States	Cancer Center of Kansas, P.A. - Parsons	Parsons	Kansas
United States	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Oncology/Hematology Associates of Central Illinois, P.C.	Peoria	Illinois
United States	OSF St. Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois Valley Community Hospital	Peru	Illinois
United States	Cancer Center of Kansas, P.A. - Pratt	Pratt	Kansas
United States	Perry Memorial Hospital	Princeton	Illinois
United States	St. Mary-Corwin Regional Medical Center	Pueblo	Colorado
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Southern Regional Medical Center	Riverdale	Georgia
United States	Hubert H. Humphrey Cancer Center at North Memorial Medical Center	Robbinsdale	Minnesota
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Rutherford Hospital	Rutherfordton	North Carolina
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Cancer Center of Kansas, P.A. - Salina	Salina	Kansas
United States	Firelands Regional Medical Center	Sandusky	Ohio
United States	North Coast Cancer Care, Incorporated	Sandusky	Ohio
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming
United States	Mercy Medical Center - Sioux City	Sioux City	Iowa
United States	Siouxland Hematology-Oncology Associates at June E. Nylen Cancer Center	Sioux City	Iowa
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	St. Luke's Regional Medical Center	Sioux City	Iowa
United States	Avera McKennan Hospital and University Health Center	Sioux Falls	South Dakota
United States	Medical X-Ray Center, P. C.	Sioux Falls	South Dakota
United States	Sioux Valley Hospital and University of South Dakota Medical Center	Sioux Falls	South Dakota
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	St. Margaret's Hospital	Spring Valley	Illinois
United States	Valley Cancer Center	Spring Valley	Illinois
United States	Park Nicollet Health Services	St. Louis Park	Minnesota
United States	United Hospital	St. Paul	Minnesota
United States	Geisinger Medical Group	State College	Pennsylvania
United States	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Promedica Cancer Center at Flower Hospital	Sylvania	Ohio
United States	North Suburban Medical Center	Thorton	Colorado
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	CCOP - Toledo Community Hospital	Toledo	Ohio
United States	Medical College of Ohio Cancer Institute	Toledo	Ohio
United States	St. Vincent Mercy Medical Center	Toledo	Ohio
United States	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio
United States	Toledo Hospital	Toledo	Ohio
United States	Toledo Surgical Specialists	Toledo	Ohio
United States	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma
United States	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Fulton County Health Center	Wauseon	Ohio
United States	Cancer Center of Kansas, P.A. - Wellington	Wellington	Kansas
United States	Medical Oncology and Hematology Associates - West Des Moines	West Des Moines	Iowa
United States	Associates in Womens Health, P.A. - North Review	Wichita	Kansas
United States	Cancer Center of Kansas, P.A. - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas, P.A. - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania
United States	Cancer Center of Kansas, P.A. - Winfield	Winfield	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

Hines SL, Mincey BA, Sloan JA, Thomas SP, Chottiner E, Loprinzi CL, Carlson MD, Atherton PJ, Salim M, Perez EA. Phase III randomized, placebo-controlled, double-blind trial of risedronate for the prevention of bone loss in premenopausal women undergoing c — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Average intra-patient change in lumbar spine (L2-L4, PA) bone mineral density (BMD) from baseline to one year after study entry		1 year post study entry	No
Secondary	Average intra-patient change in femoral neck and total hip BMD from baseline to one year after study entry		1 year post study entry	No
Secondary	Incidence of osteopenia in the risedronate vs placebo groups at one year after study entry		1 year post study entry	No
Secondary	Incidence of osteoporosis in the risedronate vs placebo groups at one year after study entry		1 year post study entry	No
Secondary	Incidence of a 5% difference in intra-patient BMD scores at baseline		Baseline	No
Secondary	Serum and urine N-telopeptide and serum alkaline phosphatase at baseline and 6 months		Up to 6 months	No
Secondary	Frequency and severity of toxicity as measured by NCI CTC version 2.0		Up to 1 year post study treatment	Yes
Secondary	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		Up to 2 years post study entry	No
Secondary	Association of baseline serum estradiol levels with permanent cessation of menses		Baseline	No
Secondary	Relationship between the subscales of the GCS (psychological, vasomotor, somatic and sexual) with type of chemotherapy, duration of chemotherapy, and menstrual cycle changes		Up to 2 years post study entry	No