Gefitinib and Etoposide in Treating Patients With Advanced Prostate Cancer That Did Not Respond to Hormone Therapy

Study Overview
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Brief Summary
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RATIONALE: Gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving gefitinib together with etoposide may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving gefitinib together with etoposide works in treating patients with advanced prostate cancer that did not respond to hormone therapy.

Detailed Description
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OBJECTIVES: Primary Determine the activity of gefitinib and etoposide, in terms of overall response rate, in patients with hormone-refractory advanced prostate cancer previously treated with docetaxel-based therapy. Secondary Determine the toxicity of this regimen in these patients. Determine whether related biomarkers can help predict response in patients treated with this regimen. OUTLINE: This is a nonrandomized study. Patients receive oral gefitinib once daily on days 1-28 and oral etoposide once daily on days 1-14. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection at baseline and periodically during study for correlative studies. Blood samples are analyzed by enzyme-linked immunosorbent assays for biomarkers (e.g., VEGF, basic fibroblast growth factor, and anti-EGFR antibody titers) in order to determine whether one or more of these biomarkers can predict response. After completion of study therapy, patients are followed periodically.

Official Title
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A Phase II Study Evaluating the Efficacy of Iressa Plus Etoposide in Patients With Advanced Hormone Refractory Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Gefitinib plus etoposide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed adenocarcinoma of the prostate Progressive disease after a prior docetaxel-based regimen OR failed a prior docetaxel-based regimen Hormone-refractory disease, meeting 1 of the following criteria: Radiologically measurable disease Prostate-specific antigen (PSA) progression* while on hormonal therapy (including withdrawal from a direct antagonist) NOTE: *If the confirmatory PSA value is less than the screening PSA value, then an additional test for rising PSA is required to document progression Must have undergone prior surgical castration OR currently be on a luteinizing hormone-releasing hormone agonistANC > 1,500/mm³Platelet count > 100,000/mm³Hemoglobin > 10 g/dL (in the absence of packed red blood cell transfusions within the past 4 weeks)Creatinine < 2 mg/dLAST and ALT < 2 times upper limit of normal (ULN)Alkaline phosphatase < 2 times ULNFertile patients must use effective double-method contraception during and for 1 month after completion of study treatmentAt least 4 weeks since prior cytotoxic therapy At least 4 weeks since prior direct antagonists, including flutamide and nilutamide At least 6 weeks since prior bicalutamide At least 30 days since prior nonapproved or investigational drugs More than 4 weeks since prior palliative radiotherapy o The irradiated lesion must not be used to assess response rate Exclusion Criteria: No other malignancy within the past 5 years except basal cell carcinoma No clinically significant New York Heart Association class II-IV cardiovascular disease No evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease) No unresolved chronic toxicity > grade 2 from prior anticancer therapy, with the exception of alopecia No other significant clinical disorder or laboratory finding that would preclude study participation No known severe hypersensitivity to gefitinib or any of the excipients of this product No evidence of clinically active interstitial lung disease o Asymptomatic Patients with chronic, stable radiographic changes are eligible No prior gefitinib or etoposide No concurrent palliative radiotherapy No concurrent chemotherapeutic agents No concurrent phenytoin, carbamazepine, rifampin, barbiturates, or Hypericum perforatum (St. John's wort) No concurrent hormones except antiandrogen therapy, steroids for adrenal failure, hormones for nondisease-related conditions (e.g., insulin for diabetes), or intermittent dexamethasone as an antiemetic No concurrent initiation of IV and/or oral bisphosphonates specifically for symptomatic bone metastases

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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Male

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: Gefitinib plus Etoposide<br>Gefitinib 250 mg p.o. daily, starting on Day 1and taken on a continuous basis throughout the trial. Etoposide 50 mg/m2/day for Days 1-14 out of a 28-day cycle. (Etoposide capsules come in a 50-mg dose formulation, and the patient's dose will be rounded to the nearest 50-mg multiple). | Drug: Gefitinib plus etoposide<br>* Gefitinib 250 mg p.o. daily, starting on Day 1and taken on a continuous basis throughout the trial with Etoposide 50 mg/m2/day for Days 1-14 out of a 28-day cycle. (Etoposide capsules come in a 50-mg dose formulation, and the patient's dose will be rounded to the nearest 50-mg multiple).<br>* Other names: ZD1839;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate as Measured by RECIST Criteria and PSA Criteria | If there is at least 1 response, then 7 additional patients will be enrolled. If there are 4 or more responders overall, then the combination will be considered active and warrant further study. Overall response rate (ORR) is defined as the proportion of patients who have a partial or complete response to therapy. | Approximately 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarkers |  | At every cycle | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the prostate, recurrent prostate cancer, stage III prostate cancer, stage IV prostate cancer