RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using LY353381 may fight breast cancer by reducing the production of estrogen.

PURPOSE: Randomized phase II trial to compare the effectiveness of two different doses of LY353381 in treating women with advanced or metastatic breast cancer.

Condition	Treatment or Intervention	Phase
stage IV breast cancer Quality of Life recurrent breast cancer	Drug: LY353381	Phase II

Further Study Details: 

OBJECTIVES: I. Compare the response rate or clinical benefit rate in patients with locally advanced or metastatic breast cancer treated with 1 of 2 different doses of LY353381.

II. Compare the response rates and clinical benefit rates for patients with tamoxifen-sensitive versus tamoxifen-refractory disease.

III. Compare the degree of toxicity between the 2 doses of LY353381 in these patients.

IV. Compare the quality of life and survival of these patients receiving high versus low dose LY353381.

V. Determine the time to progressive disease, time to treatment failure, and response duration of this treatment in these patients.

VII. Measure changes in serum estradiol, follicle stimulating hormone, luteinizing hormone, and sex hormone binding globulin in these patients during treatment.

PROTOCOL OUTLINE: This is a randomized, double blind study. Patients are stratified according to number of metastatic sites (less than 3 vs 3 or more), tamoxifen sensitivity (sensitive vs refractory), and degree of estrogen receptor positivity (high vs low vs unknown). Patients are randomized to receive 1 of 2 doses of LY353381.

Patients receive LY353381 orally once daily for 12 weeks. Treatment continues in the absence of toxicity and disease progression. Quality of life is assessed before, during, and at the completion of the study.

Patients are followed every 4 weeks for 12 weeks, at 30 days after the last treatment, and every 2-3 months after the last treatment.

PROJECTED ACCRUAL: This study will accrue 104-114 patients.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven locally advanced or metastatic breast cancer and meeting one of the following criteria: No prior systemic therapy OR Relapsed more than 12 months after stopping adjuvant tamoxifen (tamoxifen- sensitive) OR Relapsed while receiving adjuvant tamoxifen for more than 12 months (tamoxifen-refractory) OR Disease progression while receiving tamoxifen as first-line treatment for metastatic breast cancer (tamoxifen-refractory)
• Evaluable or bidimensionally measurable disease
• No rapid disease progression requiring chemotherapy
• Brain metastases allowed if stable for at least 6 months after surgery or radiotherapy, with no increase in corticosteroids
• Hormone receptor status: Estrogen receptor positive AND/OR Progesterone receptor positive OR Unknown status allowed if over 50 years old

--Prior/Concurrent Therapy--

• Biologic therapy: No concurrent immunotherapy; Concurrent hematopoietic growth factor allowed
• Chemotherapy: No prior chemotherapy for metastatic breast cancer; No concurrent chemotherapy
• Endocrine therapy: No prior hormonal therapy for metastatic breast cancer (except tamoxifen); No concurrent supplemental estrogen or progesterone; At least 3 weeks since prior estrogen replacement therapy; No other concurrent hormone therapy
• Radiotherapy: At least 2 weeks since prior radiotherapy
• Surgery: Not specified
• Other: At least 4 weeks since prior use of other investigational agents; Concurrent bisphosphonate therapy allowed; No other concurrent investigational agent

--Patient Characteristics--

• Age: 18 and over
• Sex: Female
• Menopausal status: Not specified
• Performance status: ECOG 0-1
• Life expectancy: At least 24 weeks
• Hematopoietic: Granulocyte count at least 1500/mm3; Platelet count at least 100,000/mm3; Hemoglobin at least 9 g/dL, transfusion independent
• Hepatic: Bilirubin no greater than 1.5 times normal; PT/PTT no greater than 1.25 times upper limit of normal (ULN); ALT/AST no greater than 2.5 times ULN
• Renal: Creatinine less than 1.5 times ULN; Calcium no greater than 11 mg/dL; No hypercalcemia
• Other: Not pregnant or nursing; Fertile patients must use approved nonhormonal contraceptive during and for 3 months after study; No known predisposition to thromboembolic disorder; At least 5 years since other primary malignancy except: Adequately treated nonmelanomatous skin cancer; Carcinoma in situ of the cervix; No serious concurrent systemic disorders incompatible with study

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States

Study chairs or principal investigators

Clifford A. Hudis,  Study Chair,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000066453; MSKCC-98038; NCI-G98-1451; LILLY-H4Z-MC-JWWD(a)
Record last reviewed:  September 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003428
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08