Official Title: “ZD1839 (IRESSA) In Tamoxifen-Resistant Metastatic Breast Cancer”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control

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.

Intervention(s) in this Clinical Trial

• Drug: gefitinib
• Drug: tamoxifen citrate

Primary Measures

• Clinical benefit rate (complete response, partial response, and stable disease) for 26 weeks
  • Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Norris Cotton Cancer Center

Overall Clinical Trial Officials and Contacts

Gary N. Schwartz, MD Principal Investigator Norris Cotton Cancer Center  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00080743

Study ID Number: CDR0000355145

ClinicalTrials.gov Identifier: NCT00080743

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database