Gefitinib Followed By Surgery in Treating Women With Ductal Carcinoma In Situ of the Breast
Gefitinib Followed By Surgery in Treating Women With Ductal Carcinoma In Situ of the Breast
RATIONALE: Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for
 their growth. It is not yet known whether surgery is more effective with or without gefitinib
 in treating ductal carcinoma in situ.

 PURPOSE: This randomized phase II trial is studying how well gefitinib together with surgery
 works compared to surgery alone for the treatment of women with ductal carcinoma in situ of
 the breast.
OBJECTIVES:

 Primary

 -  Compare epidermal growth factor receptor (EGFR) pathway biomarker modulation in tissue
 samples of women with ductal carcinoma in situ (DCIS) of the breast treated with
 gefitinib vs placebo followed by local surgery.

 -  Compare the effect of these regimens on cell turnover in vivo in EGFR-positive vs
 EGFR-negative patients.

 Secondary

 -  Compare the efficacy of these regimens in estrogen-receptor (ER)-positive vs ER-negative
 and in HER2-positive vs HER2-negative patients with DCIS.

 -  Correlate levels of HER2 extracellular domain with biomarker modulation in patients
 treated with these regimens.

 OUTLINE: This is a randomized, pilot study. Patients are randomized to 1 of 2 treatment arms.

 -  Arm I: Patients receive oral gefitinib once daily for 7-14 days or until the day before
 local surgery. Patients then undergo lumpectomy or mastectomy.

 -  Arm II: Patients receive oral placebo once daily for 7-14 days or until the day before
 local surgery. Patients then undergo local surgery as in arm I.

 PROJECTED ACCRUAL: A total of 78 patients (39 per treatment arm) will be accrued for this
 study within 1.5 years.
DISEASE CHARACTERISTICS:

 -  Histologically confirmed ductal carcinoma in situ (DCIS) of the breast OR mammogram
 highly suspicious for DCIS

 -  No invasive disease

 -  Not completely excised

 -  Epidermal growth factor receptor (EGFR) positive (> 10% of cells stained)

 -  Planned lumpectomy or mastectomy within the next 2-4 weeks

 -  Hormone receptor status:

 -  Estrogen receptor status known

 PATIENT CHARACTERISTICS:

 Age

 -  35 and over

 Sex

 -  Female

 Menopausal status

 -  Not specified

 Performance status

 -  ECOG 0-1

 Life expectancy

 -  Not specified

 Hematopoietic

 -  Granulocyte count > 1,500/mm^3

 -  Platelet count > 100,000/mm^3

 Hepatic

 -  Bilirubin < 1.5 mg/dL

 -  SGOT ≤ 2 times upper limit of normal (ULN)

 -  SGPT < 1.5 times ULN

 -  PT and PTT ≤ 1.5 times ULN

 -  INR ≤ 1.5 times ULN

 Renal

 -  Creatinine < 1.5 mg/dL

 Cardiovascular

 -  No New York Heart Association class I-IV heart disease

 Pulmonary

 -  No acute asthma

 Other

 -  Not pregnant or nursing

 -  Negative pregnancy test

 -  Fertile patients must use effective contraception

 -  Random blood sugar < 2.5 times ULN

 -  No known hypersensitivity to study drug or its excipients

 -  No nonhealing wound or fracture

 -  No active infection

 -  No other malignancy within the past 5 years except basal cell carcinoma, breast
 carcinoma, or carcinoma in situ of the cervix

 -  No psychosis or severe depression

 -  No other concurrent uncontrolled illness

 PRIOR CONCURRENT THERAPY:

 Biologic therapy

 -  No prior trastuzumab (Herceptin®)

 Chemotherapy

 -  At least 1 year since prior chemotherapy

 -  No concurrent chemotherapy

 Endocrine therapy

 -  At least 1 year since prior aromatase inhibitors

 -  At least 1 year since prior antiestrogens or luteinizing hormone-releasing hormone
 agonists or antagonists

 -  No concurrent glucocorticoids

 -  Concurrent oral contraceptives allowed

 -  Concurrent hormone replacement therapy allowed

 Radiotherapy

 -  At least 1 year since prior radiotherapy

 -  No concurrent radiotherapy

 Surgery

 -  See Disease Characteristics

 -  Recovered from prior oncologic or other major surgery

 -  No prior organ allograft

 Other

 -  Recovered from all prior therapy (except alopecia)

 -  More than 30 days since prior non-approved or investigational drugs

 -  No prior definitive local therapy

 -  No prior immunosuppressive therapy

 -  No prior gefitinib

 -  No other prior EGFR inhibitors

 -  No other concurrent cytotoxic drugs

 -  No concurrent warfarin for anticoagulation

 -  No concurrent CYP3A4 inducers, including any of the following:

 -  Phenytoin

 -  Carbamazepine

 -  Barbiturates

 -  Rifampin

 -  Phenobarbital

 -  Hypericum perforatum (St. John's wort)

 -  Ethosuximide

 -  Griseofulvin

 -  Nafcillin

 -  Nelfinavir

 -  Nevirapine

 -  Oxcarbazepine

 -  Phenylbutazone

 -  Primidone

 -  Rifabutin

 -  Rofecoxib

 -  Sulfamethazine

 -  Sulfinpyrazone

 -  Troglitazone

 -  No concurrent antiretroviral treatment for HIV-positive patients