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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

Phase 2
18 Years
Open (Enrolling)
Breast Cancer

Thank you

Trial Information

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


- Compare the antitumor activity of anastrozole and gefitinib vs fulvestrant and
gefitinib in postmenopausal women with recurrent or metastatic hormone
receptor-positive breast cancer.

- Compare the safety of these regimens in these patients.

- Compare the interaction of biological predictors of response in patients treated with
these regimens.

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.

ACCRUAL: A total of 148 patients (74 per treatment arm) were accrued for this study.

Inclusion Criteria

Inclusion criteria:

- Histologically confirmed adenocarcinoma of the breast (Recurrent or metastatic

- Measurable disease

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

- Estrogen and/or progesterone receptor positive

- Age>=18

- Female

- 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

- ECOG performance status of 0-2

- Adequate hematopoietic, hepatic, renal functions defined by the following within 2
weeks prior to randomization:

- Neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- Bilirubin no greater than 1.25 times upper limit of normal (ULN)

- Serum glutamic-pyruvic transaminase (ALT) and Serum glutamic-oxaloacetic (AST)
no greater than 2.5 times ULN (5 times ULN if liver metastases are present)

- International normalized ratio of prothrombin time (INR), prothrombin time (PT),
and partial thromboplastin time (PTT) normal

- Creatinine clearance at least 30 mL/min

- More than 3 weeks since prior trastuzumab (HerceptinĀ®)

- More than 3 weeks since prior chemotherapy

- More than 3 months since prior luteinizing hormone-releasing hormone agonists or
antagonists (patients 55 years old and under)

- 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

- Concurrent bisphosphonates for hypercalcemia or bone metastases are allowed

Exclusion Criteria:

- Pregnant or nursing

- Untreated ocular inflammation or infection

- Medical or psychiatric condition that would preclude study compliance, ability to
give informed consent, or assessment of response or anticipated toxic effects

- History of central nervous system (CNS) metastasis

- 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

- Contraindication to intramuscular injections

- More than 2 prior chemotherapy regimens for metastatic disease

- Prior hormonal therapy for metastatic disease

- Prior estrogen receptor down-regulators (e.g., fulvestrant) in the adjuvant setting

- Prior aromatase inhibitors (e.g., anastrozole, letrozole, exemestane, or
aminoglutethimide) in the adjuvant setting

- Prior agents that target epidermal growth factor receptors

- Other concurrent hormonal therapy

- Concurrent chemotherapy

- Concurrent trastuzumab

- Concurrent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors
(e.g., ketoconazole, erythromycin, or verapamil)

- Concurrent anticoagulants, except for thrombotic events in patients in arm I

- 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)

Type of Study:


Study Design:

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Clinical Benefit Rate

Outcome Description:

Clinical benefit = complete response (CR), partial response (PR), or stable disease (SD) lasting for at least 6 months, assessed per Response Evaluation Criteria of Solid Tumor (RECIST).CR=disappearance of all target and non-target lesions. PR= disappearance of or at least 30% decrease in the sum of the longest diameters of target lesions, with non-progressive disease in non-target lesions. SD= sum of the longest diameters of target lesions decrease <30% or increase <20%, with non-progressive disease in non-target lesions. 141 eligible, treated patients were included.

Outcome Time Frame:

assessed every 3 cycles while on treatment, assessed every 3 months when follow up <2 years, every 6 months between 2-3 years,no specific requirements after 3 years

Safety Issue:


Principal Investigator

Robert W. Carlson, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Stanford University


United States: Food and Drug Administration

Study ID:




Start Date:

September 2003

Completion Date:

Related Keywords:

  • Breast Cancer
  • recurrent breast cancer
  • stage IV breast cancer
  • metastatic breast cancer
  • postmenopausal women
  • hormone receptor-positive
  • Breast Neoplasms



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