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

Vanderbilt University Medical Center

Status and phase

Terminated

Phase 2

Conditions

Breast Cancer

Treatments

Drug: gefitinib

Procedure: Surgery

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00082667

VICC BRE 0249

P30CA068485 (U.S. NIH Grant/Contract)

VICC-BRE-0249

Details and patient eligibility

About

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.

Full description

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.

Enrollment

1 patient

Sex

Female

Ages

35+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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 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