- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00057941
Anastrozole and ZD1839 Compared With Fulvestrant and ZD1839 in Postmenopausal Women w/ Metastatic Breast Cancer
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
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. Evaluate the antitumor activity of anastrozole given in combination with the EGFR tyrosine kinase inhibitor ZD1839, and of fulvestrant given in combination with the EGFR tyrosine kinase inhibitor ZD1839.
II. Evaluate the safety of anastrozole given in combination with ZD1839 and fulvestrant given in combination with ZD1839.
III. Evaluate the interaction of biological characteristics that predict for response of breast cancer to treatment with anastrozole and ZD1839 and with fulvestrant and ZD1839.
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Massachusetts
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Boston, Massachusetts, United States, 02215
- Eastern Cooperative Oncology Group
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients must have estrogen and/or progesterone receptor positive histologically confirmed adenocarcinoma of the breast with measurable recurrent or metastatic carcinoma of the breast
- Baseline measurements and evaluations of involved sites should be performed as close as possible to study entry, but must be within 4 weeks prior to randomization
- Patients with available tissue blocks from either the primary or metastatic site must submit the tissue for EGFR analysis
All patients must be postmenopausal females defined by:
- Prior bilateral oophorectomy or bilateral ovarian irradiation
- No menstrual period for 12 months or longer. If age 55 years or less and on tamoxifen within the prior 6 months, must have an estradiol level in the postmenopausal range
- Patients must not have had more than 2 prior chemotherapy regimens for metastatic disease and no chemotherapy within 3 weeks prior to randomization; no concurrent chemotherapy is allowed while on protocol therapy
- Patients must not have prior hormonal therapy for metastatic disease; no prior therapy in the adjuvant setting with an estrogen receptor down-regulator (e.g. fulvestrant) or an aromatase inhibitor (e.g. anastrozole, letrozole, exemestane, aminoglutethamide); non-protocol concurrent hormonal therapy is not allowed
- Patients must not have had prior therapy with agents that target EGFR
- Previous, but not concomitant, therapy with trastuzumab (Herceptin) is allowed; patients must not receive trastuzumab (Herceptin) within 3 weeks prior to randomization
- Patients must have ECOG performance status of 0, 1, or 2
- Neutrophils >= 1500/mm^3
- Platelets >= 100,000/mm^3
- Bilirubin =< 1.25 x upper limit of normal
- SGPT (ALT) and SGOT (AST) =< 2.5 x upper limit of normal if no demonstrable liver metastases or =< 5 times upper limit of normal in the presence of liver metastases
- Calculated creatinine clearance >= 30ml/min
- INR, PT and PTT within normal range
- Patients must not be receiving therapy with anticoagulants or have other contraindication to i.m. injections
- Patients must not have a history of central nervous system metastasis
- Patients may receive concurrent radiation therapy to painful sites of boney disease or areas of impending fracture as long as the radiation therapy is initiated prior to study entry and sites of measurable disease outside the radiation therapy port are available to follow; patient who have received prior radiation therapy must have recovered from toxicity of the prior radiation therapy
- Patients must not take the following medications that may alter ZD1839 pharmacokinetics while enrolled in this trial: phenytoin, carbamazapine, phenobarbitol, rifampicin, and St. John's Wort, oxcarbazepine, rifapentine, modafinil, and griseofulvin
- Patients age =< 55 years must not be receiving LHRH agonists or antagonists within 3 months prior to randomization
- Patients who have an ocular inflammation or infection should be fully treated before entry into the trial; patients with a neuropathic keratopathy or diabetes or those with anterior basement membrane disease must be advised of the need for frequent opthalmalogic exams
- Patients who continue to wear contact lenses must be advised that they have an increased risk of ocular events; the decision to wear contact lenses should be discussed with the patient's treating oncologist and ophthalmologist
- Patients must not suffer from medical or psychiatric conditions that would interfere with protocol compliance, the ability to provide informed consent, or assessment of response or anticipated toxicities
- Patients must be disease-free of prior invasive malignancies for > 5 years with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm I (anastrozole, gefitinib)
Patients receive oral anastrozole and oral gefitinib once daily on days 1-28.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
|
Correlative studies
Given orally
Other Names:
Given orally
Other Names:
|
Experimental: Arm II (fulvestrant, gefitinib)
Patients receive fulvestrant intramuscularly on day 1 and oral gefitinib once daily on days 1-28.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
|
Correlative studies
Given orally
Other Names:
Given intramuscularly
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical Benefit Rate
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
|
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.
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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
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Robert Carlson, Eastern Cooperative Oncology Group
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Protein Kinase Inhibitors
- Hormone Antagonists
- Aromatase Inhibitors
- Steroid Synthesis Inhibitors
- Estrogen Antagonists
- Estrogen Receptor Antagonists
- Fulvestrant
- Gefitinib
- Anastrozole
Other Study ID Numbers
- NCI-2012-03148 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- U10CA021115 (U.S. NIH Grant/Contract)
- CDR0000285631
- E4101 (Other Identifier: CTEP)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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