Study of Tamoxifen and Raloxifene (STAR) for the Prevention of Breast Cancer in Postmenopausal Women - Full Text View

Sponsor:	National Surgical Adjuvant Breast and Bowel Project (NSABP)
Collaborators:	National Cancer Institute (NCI) Eli Lilly and Company AstraZeneca
Information provided by (Responsible Party):	National Surgical Adjuvant Breast and Bowel Project (NSABP)
ClinicalTrials.gov Identifier:	NCT00003906

Purpose

RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using raloxifene and tamoxifen may fight breast cancer by blocking the uptake of estrogen by the tumor cells.

PURPOSE: Randomized double-blinded clinical trial to compare the effectiveness of raloxifene with that of tamoxifen in preventing breast cancer in postmenopausal women.

Condition	Intervention	Phase
Breast Cancer	Drug: Raloxifene Drug: Tamoxifen	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Prevention
Official Title:	Study of Tamoxifen and Raloxifene (STAR) for the Prevention of Breast Cancer

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Tamoxifen Tamoxifen citrate Raloxifene hydrochloride Raloxifene

U.S. FDA Resources

Further study details as provided by National Surgical Adjuvant Breast and Bowel Project (NSABP):

Primary Outcome Measures:

Incidence of invasive breast cancer; superiority of one of the therapies. [ Time Frame: Time from randomization to the occurance of invasive breast cancer. ] [ Designated as safety issue: No ]
Determine which of the following is true:
1. compared to tamoxifen, raloxifene significantly reduces the incidence rate of invasive breast cancer;
2. compared to raloxifene, tamoxifen significantly reduces the incidence rate of invasive breast cancer; or
3. the statistical superiority of one of the treatments cannot be demonstrated and the choice of therapy should be based on benefit/risk considerations.

Secondary Outcome Measures:

Effect of the study therapies on the incidence of intraductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS). [ Time Frame: Time from randomization to the occurance of DCIS or LCIS. ] [ Designated as safety issue: No ]
Effect of the study therapies on the incidence of endometrial cancer. [ Time Frame: Time from randomization to the occurance of endometrial cancer. ] [ Designated as safety issue: No ]
Effect of the study therapies on the incidence of ischemic heart disease. [ Time Frame: Time from randomization to the occurance of ischimic heart disease. ] [ Designated as safety issue: No ]
Effect of the study therapies on the incidence of fractures of the hip, spine, or Colles' fractures of the wrist. [ Time Frame: Time from randomization to the occurance of fractures of the hip, spine, or Colles' fractures of the wrist. ] [ Designated as safety issue: No ]
Effect of the study therapies on the toxicity and side effects of each therapy. [ Time Frame: Incidences of protocol defined toxicities and side effects. ] [ Designated as safety issue: Yes ]
Effect of the study therapies on participants' quality of life. [ Time Frame: pre-entry, every 6 months for 5 years, and then annual after 5 years following randomization. ] [ Designated as safety issue: No ]

Enrollment:	19747
Study Start Date:	May 1999
Estimated Study Completion Date:	March 2014
Primary Completion Date:	December 2005 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Group 1 Tamoxifen and placebo	Drug: Tamoxifen 20 mg/day plus placebo for 5 years
Experimental: Group 2 Raloxifene and Placebo	Drug: Raloxifene 60 mg/day plus placebo for 5 years

Detailed Description:

OBJECTIVES:

Determine whether raloxifene is more or less effective than tamoxifen in significantly reducing the incidence rate of invasive breast cancer in postmenopausal women.
Evaluate the effects of tamoxifen and raloxifene on the incidence of intraductal carcinoma in situ, lobular carcinoma in situ, endometrial cancer, ischemic heart disease, fractures of the hip and spine, or Colles' fractures of the wrist in these participants.
Evaluate the toxic effects of these regimens in these participants.
Determine the effect of these regimens on the quality of life of these participants (at selected centers). (Quality of life evaluation closed to accrual effective 5/31/01.)

OUTLINE: This is a randomized, double-blind study. Participants are stratified by age (35 to 49 vs 50 to 59 vs over 59), race (black vs white vs other), history of lobular carcinoma in situ (yes vs no), prior hysterectomy (yes vs no), and estimated absolute risk of invasive breast cancer within 5 years (using the Gail model)(less than 2.0 vs 2.0-2.9 vs 3.0-4.9 vs 5.0 or greater). Participants are randomized to 1 of 2 arms.

Arm I: Participants receive oral tamoxifen plus placebo daily for 5 years.
Arm II: Participants receive oral raloxifene plus placebo daily for 5 years. Quality of life is assessed (at selected centers) at baseline and at 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, and 72 months. (Quality of life evaluation closed to accrual effective 5/31/01.)

Participants are followed annually after 5 years.

PROJECTED ACCRUAL: Approximately 19,000 participants will be accrued for this study within 5 years.

Eligibility

Ages Eligible for Study:	35 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Postmenopausal women at increased risk for developing invasive breast cancer, who meet one of the following criteria:
- At least 12 months since spontaneous menstrual bleeding
- Prior documented hysterectomy and bilateral salpingo-oophorectomy
- At least 55 years of age with prior hysterectomy with or without oophorectomy
- Age 35 to 54 with a prior hysterectomy without oophorectomy OR with a status of ovaries unknown with documented follicle-stimulating hormone level demonstrating elevation in postmenopausal range
Histologically confirmed lobular carcinoma in situ treated by local excision only OR a minimum projected 5 year probability of invasive breast cancer of at least 1.66%, using Breast Cancer Risk Assessment Profile
No clinical evidence of malignancy on physical exam within the past 180 days
No evidence of suspicious or malignant disease on bilateral mammogram within the past year
No bilateral or unilateral prophylactic mastectomy
No prior invasive breast cancer or intraductal carcinoma in situ
Hormone receptor status:
- Not specified

PATIENT CHARACTERISTICS:

Age:

35 and over

Sex:

Female

Menopausal status:

See Disease Characteristics

Performance status:

No restricted normal activity for a significant portion of each day

Life expectancy:

At least 10 years

Hematopoietic:

Granulocyte count at least 1,500/mm^3
Complete blood count and differential normal
Platelet count normal

Hepatic:

SGOT or SGPT normal
Bilirubin normal
Alkaline phosphatase normal

Renal:

Creatinine normal

Cardiovascular:

No cerebral vascular accident, transient ischemic attack, atrial fibrillation, or uncontrolled hypertension
No deep vein thrombosis

Pulmonary:

No pulmonary embolus

Other:

No other prior malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
No concurrent nonmalignant disease that would preclude administration of tamoxifen or raloxifene
No clinical depression, psychiatric condition, or addictive disorder
No uncontrolled diabetes

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

Not specified

Endocrine therapy:

At least 3 months since prior estrogen or progesterone replacement therapy, oral contraceptives, androgens, luteinizing hormone-releasing hormone analogs, prolactin inhibitors, or antiandrogens
At least 3 months since prior tamoxifen, raloxifene, or other selective estrogen-receptor modulators of less than 3 months duration
Concurrent Estring allowed

Radiotherapy:

No prior breast radiotherapy

Surgery:

See Disease Characteristics

Other:

No prior systemic adjuvant therapy for breast cancer
No other participation in a cancer prevention or osteoporosis prevention study involving pharmacologic intervention(s)
- NSABP-P-1 patients who received placebo are eligible
No concurrent warfarin or cholestyramine
Concurrent calcitonin or nonhormonal medication (e.g., cholecalciferol, fluoride, or bisphosphonates) allowed

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003906

Show 516 Study Locations

Sponsors and Collaborators

National Surgical Adjuvant Breast and Bowel Project (NSABP)

National Cancer Institute (NCI)

Eli Lilly and Company

AstraZeneca

Investigators

Study Chair:

Norman Wolmark, MD

NSABP Foundation, Inc.

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Vogel VG. The NSABP Study of Tamoxifen and Raloxifene (STAR) trial. Expert Rev Anticancer Ther. 2009 Jan;9(1):51-60.

Wickerham DL, Costantino JP, Vogel VG, Cronin WM, Cecchini RS, Ford LG, Wolmark N. The use of tamoxifen and raloxifene for the prevention of breast cancer. Recent Results Cancer Res. 2009;181:113-9.

Ganz PA, Land SR, Wickerham DL, et al.: The Study of Tamoxifen and Raloxifene (STAR): Change in patient-reported outcomes (PROs) after the end of treatment. [Abstract] J Clin Oncol 25 (Suppl 18): A-1506, 2007.

Ganz PA, Land SR, Wickerham DL, et al.: The study of tamoxifen and raloxifene (STAR): first report of patient-reported outcomes (PROs) from the NSABP P-2 breast cancer prevention study. [Abstract] J Clin Oncol 24 (Suppl 18): A-LBA561, 2006.

Land SR, Wickerham DL, Costantino JP, Ritter MW, Vogel VG, Lee M, Pajon ER, Wade JL 3rd, Dakhil S, Lockhart JB Jr, Wolmark N, Ganz PA. Patient-reported symptoms and quality of life during treatment with tamoxifen or raloxifene for breast cancer prevention: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA. 2006 Jun 21;295(23):2742-51. Epub 2006 Jun 5.

Vogel VG, Costantino JP, Wickerham DL, et al.: The effects of tamoxifen versus raloxifene on the risk of developing noninvasive breast cancer in the NSABP study of tamoxifen and raloxifene (STAR) P-2 trial. [Abstract] Breast Cancer Res Treat 100 (Suppl 1): A-33, S16, 2006.

Vogel VG, Costantino JP, Wickerham DL, Cronin WM, Cecchini RS, Atkins JN, Bevers TB, Fehrenbacher L, Pajon ER Jr, Wade JL 3rd, Robidoux A, Margolese RG, James J, Lippman SM, Runowicz CD, Ganz PA, Reis SE, McCaskill-Stevens W, Ford LG, Jordan VC, Wolmark N; National Surgical Adjuvant Breast and Bowel Project (NSABP). Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA. 2006 Jun 21;295(23):2727-41. Epub 2006 Jun 5. Erratum in: JAMA. 2006 Dec 27;296(24):2926.

Cronin WM, Cecchini RS, Wickerham DL, et al.: Factors associated with participant adherence in the NSABP Study of Tamoxifen and Raloxifene (STAR). [Abstract] J Clin Oncol 26 (Suppl 15): A-6518, 2008.

Land SR, Ritter MW, Costantino JP, Julian TB, Cronin WM, Haile SR, Wolmark N, Ganz PA. Compliance with patient-reported outcomes in multicenter clinical trials: methodologic and practical approaches. J Clin Oncol. 2007 Nov 10;25(32):5113-20. Review.

Gradishar WJ, Cella D. Selective estrogen receptor modulators and prevention of invasive breast cancer. JAMA. 2006 Jun 21;295(23):2784-6. Epub 2006 Jun 5. No abstract available.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Goetz MP, Schaid DJ, Wickerham DL, Safgren S, Mushiroda T, Kubo M, Batzler A, Costantino JP, Vogel VG, Paik S, Carlson EE, Flockhart DA, Wolmark N, Nakamura Y, Weinshilboum RM, Ingle JN, Ames MM. Evaluation of CYP2D6 and efficacy of tamoxifen and raloxifene in women treated for breast cancer chemoprevention: results from the NSABP P1 and P2 clinical trials. Clin Cancer Res. 2011 Nov 1;17(21):6944-51. Epub 2011 Aug 31.

Vogel VG, Costantino JP, Wickerham DL, Cronin WM, Cecchini RS, Atkins JN, Bevers TB, Fehrenbacher L, Pajon ER, Wade JL 3rd, Robidoux A, Margolese RG, James J, Runowicz CD, Ganz PA, Reis SE, McCaskill-Stevens W, Ford LG, Jordan VC, Wolmark N; National Surgical Adjuvant Breast and Bowel Project. Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: Preventing breast cancer. Cancer Prev Res (Phila Pa). 2010 Jun;3(6):696-706. Epub 2010 Apr 19.

Responsible Party:	National Surgical Adjuvant Breast and Bowel Project (NSABP)
ClinicalTrials.gov Identifier:	NCT00003906 History of Changes
Other Study ID Numbers:	NSABP P-2, CDR0000067081
Study First Received:	November 1, 1999
Last Updated:	September 20, 2011
Health Authority:	United States: Food and Drug Administration; United States: Federal Government; United States: Institutional Review Board; Canada: Ethics Review Committee; Canada: Health Canada

Keywords provided by National Surgical Adjuvant Breast and Bowel Project (NSABP):

breast cancer

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Tamoxifen
Raloxifene
Antineoplastic Agents, Hormonal
Antineoplastic Agents

Therapeutic Uses
Pharmacologic Actions
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Bone Density Conservation Agents
Estrogen Antagonists

ClinicalTrials.gov processed this record on February 13, 2012