A Phase II And Biologic Correlative Study Investigating ARIMIDEX In Combination With IRESSA (ZD1839) In Post-Menopausal Patients With Estrogen Receptor-Positive Metastatic Breast Carcinoma Who Have Previously Failed Hormonal Therapy
18 Years
N/A
Female
Breast Cancer
Trial Information
A Phase II And Biologic Correlative Study Investigating ARIMIDEX In Combination With IRESSA (ZD1839) In Post-Menopausal Patients With Estrogen Receptor-Positive Metastatic Breast Carcinoma Who Have Previously Failed Hormonal Therapy
OBJECTIVES:
- Determine the antitumor activity of anastrozole and ZD 1839, as measured by objective
response (partial or complete) or stable disease at 6 months, in post-menopausal women
with estrogen receptor-positive, hormone refractory, metastatic breast cancer.
- Determine the progression-free and overall survival of patients treated with this
regimen.
- Determine the safety of this regimen in these patients.
- Determine the pharmacokinetics of this regimen in these patients.
- Correlate molecular markers with clinical benefit in patients treated with this
regimen.
OUTLINE: This is an open-label, multicenter study.
Patients are stratified according to prior objective response to endocrine therapy (yes vs
no).
Patients receive oral anastrozole once daily alone for 2 weeks. Patients then receive oral
anastrozole and oral ZD 1839 once daily for 28 days. Courses repeat every 28 days in the
absence of disease progression or unacceptable toxicity.
Patients are followed at 1 month and then monthly thereafter.
PROJECTED ACCRUAL: A total of 36-78 patients (18-39 per stratum) will be accrued for this
study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed breast cancer
- Metastatic or locally advanced unresectable disease
- At least 1 measurable target lesion that has not been irradiated
- New lesions in a previously irradiated field allowed as sites of measurable
disease
- Progressive disease after more than 2 months of aromatase inhibitor therapy
- No known CNS disease or unevaluated CNS symptoms suggestive of brain metastases
- Hormone receptor status:
- Estrogen receptor or progesterone receptor positive
PATIENT CHARACTERISTICS:
Age
- 18 and over
Sex
- Female
Menopausal status
- Post-menopausal by 1 of the following criteria:
- Age 50 and over and has not menstruated during the past year or has castrate
follicle-stimulating hormone (FSH) levels (greater than 40 IU/L)
- Under age 50 and has castrate FSH levels
- Received prior bilateral oophorectomy and has castrate FSH levels
Performance status
- ECOG 0-2
Life expectancy
- At least 12 weeks
Hematopoietic
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
Hepatic
- Bilirubin no greater than 1.5 times upper limit of normal (ULN)
- ALT or AST no greater than 2.5 times ULN (5 times ULN if liver metastases present)
Renal
- Creatinine no greater than 1.5 times ULN
Cardiovascular
- No history of congestive heart failure requiring therapy
- No ventricular arrhythmia requiring therapy
- No unstable angina pectoris
- No myocardial infarction within the past 6 months
Other
- Able to swallow oral medication
- No other malignancy within the past 5 years except nonmelanoma skin cancer or
carcinoma in situ of the cervix
- No known malabsorption condition or other condition that would impair absorption of
study drug
- No active infection
- No other concurrent medical condition that would preclude study
- No known severe hypersensitivity to ZD 1839 or any excipients
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- No prior chemotherapy except in adjuvant setting
- No concurrent chemotherapy for breast cancer
Endocrine therapy
- See Disease Characteristics
- More than 30 days since other prior hormonal therapy (including hormone replacement
therapy and megestrol)
- Concurrent steroids for other reasons besides skin toxicity allowed
- No other concurrent hormonal therapy (including megestrol) for breast cancer
Radiotherapy
- See Disease Characteristics
Surgery
- Recovered from prior oncologic or other major surgery
- No concurrent ophthalmic surgery
Other
- More than 30 days since prior anticancer therapy
- More than 30 days since prior non-approved or investigational drugs
- No prior epidermal growth factor receptor or HER2 blockers
- No concurrent phenytoin, carbamazepine, barbiturates, rifampicin, phenobarbital,
Hypericum perforatum, or systemic retinoids
- No other concurrent investigational therapy for breast cancer
- Concurrent bisphosphonates for metastatic bone disease allowed
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
Eric K. Rowinsky, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Cancer Therapy and Research Center, Texas
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000257752
NCT ID:
NCT00049062
Start Date:
September 2002
Completion Date:
October 2007
Related Keywords:
- Breast Cancer
- recurrent breast cancer
- stage IIIB breast cancer
- stage IIIC breast cancer
- stage IV breast cancer
- Breast Neoplasms
Name | Location |
|---|---|
| Cancer Therapy and Research Center | San Antonio, Texas 78229 |
