Gefitinib in Treating Patients With Persistent or Recurrent Endometrial Cancer

Study Overview
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Brief Summary
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Phase II trial to study the effectiveness of gefitinib in treating patients who have persistent or recurrent endometrial cancer. Biological therapies such as gefitinib may interfere with the growth of tumor cells and slow the growth of endometrial cancer.

Detailed Description
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OBJECTIVES: I. Determine the 6-month progression-free survival of patients with persistent or recurrent endometrial carcinoma after receiving gefitinib. II. Determine the nature and degree of toxicity of this drug in these patients. III. Determine the progression-free and overall survival of patients treated with this drug. IV. Determine the effects of this drug on the levels of epidermal growth factor receptors (EGFR), c-ErbB2 (HER-2/neu) receptors, estrogen receptors (ER), and progesterone receptors (PR) (both PR and PRB) in tumor specimens of these patients. V. Determine if an association exists between the levels of EGFR, ER, PR, PRB, and HER-2/neu serum concentrations of gefitinib, gefitinib activity, and soluble EGFR and clinical outcome in patients treated with this drug. VI. Determine the frequency of clinical response (partial and complete response) in patients treated with this drug. OUTLINE: This is a multicenter study. Patients receive oral gefitinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 22-60 patients will be accrued for this study within 2.5-6 years.

Official Title
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A Phase II Trial of ZD 1839 (IRESSA) (NSC #715055) in the Treatment of Persistent or Recurrent Endometrial Carcinoma

Conditions
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Recurrent Uterine Corpus Carcinoma

Intervention / Treatment
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* Drug: Gefitinib
* Other: Laboratory Biomarker Analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed primary endometrial carcinoma Recurrent or persistent disease Received 1 prior chemotherapy regimen for endometrial carcinoma Initial treatment may include high-dose, consolidation, or extended therapy administered after surgical or nonsurgical assessment At least 1 unidimensionally measurable lesion At least 20 mm by conventional techniques (including palpation, plain x-ray, CT scan, and MRI) At least 10 mm by spiral CT scan Must have at least 1 target lesion for response assessment Tumors within a previously irradiated field are designated as non-target lesions Disease in a previously irradiated field as the only site of measurable disease is allowed only if there has been clear progression of the lesion since the completion of radiotherapy Must have a tumor that is accessible for guided core needle or fine needle biopsy Ineligible for a higher priority GOG protocol, defined as any active phase III protocol for the same patient population, if one exists Performance status - GOG 0-2 (for patients who received 1 prior regimen) Performance status - GOG 0-1 (for patients who received 2 prior regimens) Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Bilirubin no greater than 1.5 times upper limit of normal (ULN) SGOT no greater than 2.5 times ULN Alkaline phosphatase no greater than 2.5 times ULN Creatinine no greater than 1.5 times ULN No unstable cardiac disease or myocardial infarction within the past 6 months History of coronary artery disease, congestive heart failure, or dysrhythmia allowed if on a stable regimen for at least 3 months No active infection requiring antibiotics No active corneal disease (e.g., keratoconjunctivitis) No grade 2 or greater sensory and motor neuropathy No other invasive malignancy within the past 5 years except nonmelanoma skin cancer No signs or symptoms of bowel dysfunction that would preclude successful ingestion of oral study medication Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception At least 3 weeks since prior immunologic agents directed at malignant tumor No concurrent anticancer immunotherapy See Disease Characteristics At least 3 weeks since prior chemotherapy directed at the malignant tumor and recovered No prior non-cytotoxic chemotherapy for recurrent or persistent disease No concurrent anticancer chemotherapy At least 1 week since prior hormonal therapy directed at malignant tumor No concurrent anticancer hormonal therapy See Disease Characteristics At least 3 weeks since prior radiotherapy directed at malignant tumor and recovered No concurrent anticancer radiotherapy At least 4 weeks since prior surgery except minor procedures using local anesthesia (e.g., placement of a central venous port) and recovered At least 3 weeks since any other prior therapy directed at malignant tumor One additional prior cytotoxic regimen for recurrent or persistent disease allowed No prior gefitinib or other epidermal growth factor receptor inhibitor No prior cancer treatment that would contraindicate study therapy No concurrent CYP 3A4 inducers (including phenytoin, carbamazepine, barbiturates, nafcillin, rifampin, or Hypericum perforatum [St. John's Wort]) No other concurrent investigational or antineoplastic agents No concurrent chlorpromazine

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (gefitinib)<br>Patients receive oral gefitinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Drug: Gefitinib<br>* Given orally<br>* Other names: ZD 1839;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients alive and progression-free |  | 6 months | 
| Frequency and severity of adverse effects as assessed by National Cancer Institute Common Toxicity Criteria (CTC) v2.0 |  | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of progression-free survival |  | Up to 5 years | 
| Duration of overall survival |  | Up to 5 years | 
| Frequency of clinical response utilizing the Gynecologic Oncology Group (GOG) Response Evaluation Criteria in Solid Tumors (RECIST) criteria |  | Up to 5 years | 
| Numerical descriptions of serum concentrations of gefitinib, gefitinib activity, and soluble epidermal growth factor receptor (EGFR) |  | Baseline to end of course 5 | 
| Initial performance status and histological grade |  | Baseline to end of course 5 |