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 giving gefitinib together with surgery works compared to surgery alone in treating women with ductal carcinoma in situ of the breast.

Condition	Treatment or Intervention	Phase
breast cancer in situ intraductal breast carcinoma	Drug: gefitinib  Procedure: conventional surgery  Procedure: enzyme inhibitor therapy  Procedure: neoadjuvant therapy  Procedure: protein tyrosine kinase inhibitor therapy  Procedure: surgery	Phase II

Further Study Details: 

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.

Tertiary

• 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.

Ages Eligible for Study:  35 Years and above,  Genders Eligible for Study:  Both

Criteria

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 nonapproved 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
• Neflinavir
• Nevirapine
• Oxcarbazepine
• Phenylbutazone
• Primidone
• Rifabutin
• Rofecoxib
• Sulfamethazine
• Sulfinpyrazone
• Troglitazone
• No concurrent antiretroviral treatment for HIV-positive patients

Tennessee
      Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center, Nashville,  Tennessee,  37232-6838,  United States; Recruiting

Study chairs or principal investigators

Cristina I. Truica, MD,  Principal Investigator,  Vanderbilt-Ingram Cancer Center   

Study ID Numbers:  CDR0000355152; VICC-BRE-0249; NCT00082667
Record last reviewed:  April 2004
Last Updated:  March 10, 2005
Record first received:  May 14, 2004
ClinicalTrials.gov Identifier:  NCT00082667
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08