Gefitinib Followed By Surgery in Treating Women With Ductal Carcinoma In Situ of the Breast

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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EGFR Pathway Modulation In Patients With Ductal Carcinoma In Situ Of The Breast

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: gefitinib
* Procedure: Surgery


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: gefitinib|nan|
|Procedure: Surgery|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 surgery. |  | at time of surgery, after 7-14 days of gefitinib | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the effect of gefitinib vs. placebo, followed by surgery on cell turnover in vivo in EGFR-positive vs. EGFR-negative patients |  | at time of surgery, after 7-14 days of gefitinib | 
| Compare the effects of gefitinib in ER-positive vs. ER-negative DCIS and in HER2-positive vs. HER2-negative DCIS |  | at time of surgery, after 7-14 days of gefitinib | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer in situ, ductal breast carcinoma in situ