Breast Cancer Clinical Trial
Gefitinib With or Without Tamoxifen in Treating Patients With Tamoxifen-Resistant Metastatic Breast Cancer
Summary
RATIONALE: Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Hormone therapy using tamoxifen may fight breast cancer by blocking the use of estrogen by the tumor cells. Combining gefitinib with tamoxifen may be effective in killing tumor cells that have become resistant (stopped responding) to tamoxifen.
PURPOSE: This randomized phase II trial is studying how well giving gefitinib together with tamoxifen works compared to gefitinib alone in treating patients with metastatic breast cancer that has stopped responding to tamoxifen.
Full Description
OBJECTIVES:
Primary
Compare the rate of clinical benefit in patients with tamoxifen-resistant breast cancer treated with gefitinib with or without tamoxifen.
Secondary
Determine the toxic effects of these regimens in these patients.
Determine whether changes in fludeoxyglucose F 18 uptake by positron emission tomography scan and changes in plasma DNA levels are indicators of an early response to gefitinib in these patients.
Determine the pharmacokinetics of these regimens in these patients.
OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified according to population (intent-to-treat population comprising all patients who receive 1 dose of treatment vs a subset of the intent-to-treat population, excluding patients with nonmeasurable/evaluable only disease). Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients receive oral tamoxifen once daily. Beginning 14 days after the start of tamoxifen, patients receive oral gefitinib once daily.
Arm II: Patients receive oral placebo once daily. Beginning 14 days after the start of placebo, patients receive oral gefitinib as in arm I.
In both arms, treatment continues for 26 weeks in the absence of disease progression or unacceptable toxicity.
Patients are followed for 6 months.
PROJECTED ACCRUAL: A total of 46 patients (23 per treatment arm) will be accrued for this study within 23 months.
Eligibility Criteria
DISEASE CHARACTERISTICS:
Histologically confirmed breast cancer
Metastatic disease
Initial clinical benefit from tamoxifen for metastatic disease, defined by 1 of the following:
Stable disease for 24 weeks or longer
Objective tumor response
Documentation of clinical progression on tamoxifen within the past 6 weeks
Hormone receptor status:
Estrogen or progesterone receptor positive on most recently analyzed biopsy
PATIENT CHARACTERISTICS:
Age
18 and over
Sex
Not specified
Menopausal status
Not specified
Performance status
ECOG 0-2
Life expectancy
At least 6 months
Hematopoietic
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hepatic
AST ≤ 1.5 times upper limit of normal (ULN)
Bilirubin ≤ 1.5 times ULN
Renal
Creatinine ≤ 1.5 times ULN OR
Creatinine clearance ≥ 50 mL/min
Pulmonary
No clinically active interstitial lung disease
Patients with asymptomatic chronic stable radiographic changes are eligible
Other
Not pregnant or nursing
Fertile patients must use effective contraception
No known hypersensitivity to gefitinib
No other malignancy within the past 5 years except basal cell carcinoma or carcinoma in situ of the cervix
PRIOR CONCURRENT THERAPY:
Biologic therapy
No concurrent trastuzumab (Herceptin®)
Chemotherapy
No concurrent cytotoxic chemotherapy
Endocrine therapy
See Disease Characteristics
At least 2 weeks since other prior tamoxifen
No concurrent hormone replacement therapy
No other concurrent antiestrogens, including raloxifene
No concurrent aromatase inhibitors
No concurrent megestrol
Concurrent systemic steroids for reasons other than skin toxicity allowed provided the steroids were initiated before study entry AND dose remains stable
Radiotherapy
Concurrent palliative radiotherapy as short-term treatment for symptomatic bone metastases allowed provided other evaluable sites of disease are present AND treatment lasts no more than 14 days
Surgery
Recovered from prior oncologic or other major surgery
No concurrent surgery during and for 7 days after study treatment
No concurrent ophthalmic surgery
Other
Recovered from all prior therapy (except alopecia)
More than 30 days since prior investigational drugs
No other concurrent investigational agents
No concurrent administration of any of the following:
Phenytoin
Carbamazepine
Barbiturates
Rifampin
Phenobarbital
Hypericum perforatum (St. John's wort)
Systemic retinoids
CYP3A4 inhibitors (e.g., itraconazole)
Drugs that cause significant sustained elevation in gastric pH ≥ 5
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There is 1 Location for this study
Lebanon New Hampshire, 03756, United States
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