Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Anastrozole and Gefitinib Compared With Fulvestrant and Gefitinib in Treating Postmenopausal Women With Recurrent or Metastatic Breast Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	18 and over	NCI	ECOG-4101 E4101, NCT00057941

Objectives

1. Compare the antitumor activity of anastrozole and gefitinib vs fulvestrant and gefitinib in postmenopausal women with recurrent or metastatic hormone receptor-positive breast cancer.
2. Compare the safety of these regimens in these patients.
3. Compare the interaction of biological predictors of response in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically confirmed adenocarcinoma of the breast
  • Recurrent or metastatic disease



• Measurable disease



• Patients with available tissue blocks from either the primary or metastatic site must submit the tissue for epidermal growth factor receptor analysis



• No history of CNS metastasis



• Hormone receptor status:
  • Estrogen and/or progesterone receptor positive

Prior/Concurrent Therapy:

Biologic therapy

• More than 3 weeks since prior trastuzumab (Herceptin®)
• No concurrent trastuzumab

Chemotherapy

• More than 3 weeks since prior chemotherapy
• No more than 2 prior chemotherapy regimens for metastatic disease
• No concurrent chemotherapy

Endocrine therapy

• More than 3 months since prior luteinizing hormone-releasing hormone agonists or antagonists (patients 55 years old and under)
• No prior hormonal therapy for metastatic disease
• No prior estrogen receptor down-regulators (e.g., fulvestrant) in the adjuvant setting
• No prior aromatase inhibitors (e.g., anastrozole, letrozole, exemestane, or aminoglutethimide) in the adjuvant setting
• No other concurrent hormonal therapy

Radiotherapy

• Recovered from prior radiotherapy
• Concurrent radiotherapy to painful sites of bony disease or areas of impending fracture is allowed provided the following conditions are met:
  • Therapy was initiated prior to study entry
  • Sites of measurable disease outside the radiotherapy port are available for disease evaluation

Surgery

• Not specified

Other

• No prior agents that target epidermal growth factor receptors
• No concurrent CYP3A4 inhibitors (e.g., ketoconazole, erythromycin, or verapamil)
• No concurrent anticoagulants, except for thrombotic events in patients in arm I
• No concurrent medications that would alter the pharmacokinetics of gefitinib (e.g., phenytoin, carbamazepine, phenobarbital, rifampin, Hypericum perforatum [St. John's wort], oxcarbazepine, rifapentine, modafinil, and griseofulvin)
• Concurrent bisphosphonates for hypercalcemia or bone metastases are allowed

Patient Characteristics:

Age

• 18 and over

Sex

• Female

Menopausal status

• Postmenopausal* defined by 1 of the following:
  • Prior bilateral oophorectomy or bilateral ovarian irradiation
  • No menstrual period for at least 12 months

 [Note: *If age 55 and under and on tamoxifen within the past 6 months, must have an estradiol level in the postmenopausal range]

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³

Hepatic

• Bilirubin no greater than 1.25 times upper limit of normal (ULN)
• ALT and AST no greater than 2.5 times ULN (5 times ULN if liver metastases are present)
• INR, PT, and PTT normal

Renal

• Creatinine clearance at least 30 mL/min

Other

• Not pregnant or nursing
• No untreated ocular inflammation or infection
• No medical or psychiatric condition that would preclude study compliance, ability to give informed consent, or assessment of response or anticipated toxic effects
• No other invasive malignancies within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No contraindication to intramuscular injections

Expected Enrollment

A total of 148 patients (74 per treatment arm) will be accrued for this study within 2 years.

Outcomes

Clinical benefit (i.e., complete response, partial response, or stable disease)

Toxicity

Outline

This is a randomized, open-label study. Patients are stratified according to prior hormonal therapy (yes vs no) and dominant site of disease (soft tissue/lymph nodes vs bone vs visceral). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral anastrozole and oral gefitinib once daily on days 1-28.



• Arm II: Patients receive fulvestrant intramuscularly on day 1 and oral gefitinib once daily on days 1-28.

Courses in both arms repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 1 year.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Robert Carlson, MD, Protocol chair		Ph: 650-725-6457; 800-756-9000

Registry Information
Official Title		A Randomized Phase II Trial of Combination Anastrozole (NSC #719344) Plus ZD1839 (Iressa, NSC #715055, IND #61187) and of Combination Fulvestrant (NSC #719276) Plus ZD1839 in the Treatment of Postmenopausal Women with Hormone Receptor-Positive Metastatic Breast Cancer
Trial Start Date		2003-09-16
Trial Completion Date		2009-09-16 (estimated)
Registered in ClinicalTrials.gov		NCT00057941
Date Submitted to PDQ		2003-02-06
Information Last Verified		2008-10-22
NCI Grant/Contract Number		CA21115

Back to Top