RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using tamoxifen or LY353381 may fight breast cancer by blocking the uptake of estrogen. PURPOSE: Randomized phase I trial to compare the effectiveness of tamoxifen with that of LY353381 in treating women who have newly diagnosed breast cancer.

Condition	Treatment or Intervention	Phase
stage I breast cancer intraductal breast carcinoma stage II breast cancer breast cancer in situ	Procedure: hormone therapy  Procedure: endocrine therapy  Procedure: antiestrogen therapy  Drug: LY353381 hydrochloride  Drug: tamoxifen	Phase I

Further Study Details: 

OBJECTIVES: I. Determine whether LY353381 hydrochloride or tamoxifen administered in the interval between biopsy and re-excision alters the expression of tissue biomarkers relative to placebo controls in postmenopausal women with newly diagnosed breast cancer.

PROTOCOL OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Phase I: Patients are randomized to receive either oral LY353381 hydrochloride or oral placebo daily. Upon completion of phase I, all treatment centers begin phase II of the study. Phase II: Patients are randomized to receive either oral tamoxifen or oral placebo daily. Treatment in both phases continues for 2-6 weeks (until scheduled lumpectomy or mastectomy) in the absence of disease progression or unacceptable toxicity. Patients are followed at 1 and 2 weeks after surgery.

PROJECTED ACCRUAL: A minimum of 120 patients (60 per treatment phase) will be accrued for this study within 18 months.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed noninvasive or small invasive breast cancer: Low or intermediate grade (ductal carcinoma in situ, T1, or T2) OR Estrogen and/or progesterone receptor positive; Largest mass no greater than 5 cm; Clustered microcalcifications as only abnormality allowed with no upper size limit; If no distinction between mass and microcalcifications, size as 1 lesion
• Lumpectomy or mastectomy must be planned for 2-6 weeks from start of study
• No evidence of metastases from any malignancy
• Hormone receptor status: Estrogen and progesterone receptor positive (unless low or intermediate grade tumor)

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: At least 1 year since prior chemotherapy
• Endocrine therapy: At least 1 year since prior aromatase inhibitors, antiestrogens, or LH agonists/antagonists; No concurrent hormone replacement therapy or oral contraceptives (from time of randomization)
• Radiotherapy: Not specified
• Surgery: See Disease Characteristics
• Other: No concurrent treatment for other malignancy

--Patient Characteristics--

• Age: 18 and over
• Sex: Female
• Menopausal status: Postmenopausal by one of the following: Prior oophorectomy; Over age 50 with prior hysterectomy, ovaries remaining; Uterus and ovaries intact and no menstrual period for more than 3 months
• Performance status: Not specified
• Life expectancy: Not specified
• Hematopoietic: Platelet count greater than 100,000/mm3; Hemoglobin greater than 10 g/dL; Absolute granulocyte count greater than 1,000/mm3
• Hepatic: Albumin greater than 3 g/dL; Bilirubin less than 1.5 mg/dL; AST less than 100 U/L; Alkaline phosphatase less than 200 U/L
• Renal: Creatinine less than 1.5 mg/dL
• Cardiovascular: No history of deep vein thrombosis
• Pulmonary: No prior pulmonary embolus
• Other: Not pregnant or nursing

Alabama
      University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham,  Alabama,  35294-3300,  United States
California
      Comprehensive Cancer Centers of the Desert, Palm Springs,  California,  92262,  United States
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States
Illinois
      Loyola University Medical Center, Maywood,  Illinois,  60153,  United States
Kansas
      University of Kansas Medical Center, Kansas City,  Kansas,  66160-7357,  United States
Ohio
      Arthur G. James Cancer Hospital - Ohio State University, Columbus,  Ohio,  43210-1240,  United States
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195,  United States
Pennsylvania
      Kimmel Cancer Center of Thomas Jefferson University - Philadelphia, Philadelphia,  Pennsylvania,  19107-5541,  United States
Texas
      U.S. Oncology Research Inc., Dallas,  Texas,  75246,  United States

Study chairs or principal investigators

Carol J. Fabian,  Study Chair,  University of Kansas   

Study ID Numbers:  CDR0000067956; KUMC-7813-99; NCI-P00-0158; KUMC-HSC-7419-98
Record last reviewed:  August 2003
Last Updated:  October 13, 2004
Record first received:  June 2, 2000
ClinicalTrials.gov Identifier:  NCT00005886
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08