Clinical trial NCT00005886: Tamoxifen Compared With LY353381 in Treating Women With Newly Diagnosed Breast Cancer
Official title: A Phase IB Randomized Study of an Antiestrogen in Women With Newly Diagnosed Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Keywords: stage I breast cancer
stage II breast cancer
ductal breast carcinoma in situ
breast cancer in situ
Lead sponsor: University of Kansas Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-08-29
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using tamoxifen or LY353381 may fight breast cancer by blocking the use of estrogen.

PURPOSE: This randomized phase I trial is studying how well tamoxifen works on the biomarkers of the tumor tissue, compared with LY353381, in treating women with newly diagnosed breast cancer.

Detailed description: OBJECTIVES:

* 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.

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.

Eligibility 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)

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/mm\^3
* Hemoglobin greater than 10 g/dL
* Absolute granulocyte count greater than 1,000/mm\^3

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

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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Comprehensive Cancer Center
state: Alabama
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center, UCLA
state: California
city: Palm Springs
country: United States
facility: Comprehensive Cancer Centers of the Desert
state: California
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital - Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: Kimmel Cancer Center of Thomas Jefferson University - Philadelphia
state: Pennsylvania
city: Dallas
country: United States
facility: U.S. Oncology Research Inc.
state: Texas
Study officials:
affiliation: University of Kansas
name: Carol J. Fabian, MD
role: STUDY_CHAIR
References:
citation: Fabian CJ, Kimler BF, Anderson J, Tawfik OW, Mayo MS, Burak WE Jr, O'Shaughnessy JA, Albain KS, Hyams DM, Budd GT, Ganz PA, Sauter ER, Beenken SW, Grizzle WE, Fruehauf JP, Arneson DW, Bacus JW, Lagios MD, Johnson KA, Browne D. Breast cancer chemoprevention phase I evaluation of biomarker modulation by arzoxifene, a third generation selective estrogen receptor modulator. Clin Cancer Res. 2004 Aug 15;10(16):5403-17. doi: 10.1158/1078-0432.CCR-04-0171.