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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00483561
Recruitment Status : Terminated (PI left UNMC)
First Posted : June 7, 2007
Results First Posted : July 17, 2018
Last Update Posted : December 18, 2018
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Elizabeth Reed, MD, University of Nebraska

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Gefitinib plus etoposide Phase 2

Detailed Description:



  • 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.


  • 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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study Evaluating the Efficacy of Iressa Plus Etoposide in Patients With Advanced Hormone Refractory Prostate Cancer
Study Start Date : January 2004
Actual Primary Completion Date : January 2010
Actual Study Completion Date : January 2010

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Gefitinib plus Etoposide

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
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).
Other Names:
  • Iressa
  • ZD1839

Primary Outcome Measures :
  1. Overall Response Rate as Measured by RECIST Criteria and PSA Criteria [ Time Frame: Approximately 3 years ]
    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.

Secondary Outcome Measures :
  1. Biomarkers [ Time Frame: At every cycle ]

Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No


  • 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 underwent prior surgical castration OR currently be on a luteinizing hormone-releasing hormone agonist


  • ANC > 1,500/mm³
  • Platelet count > 100,000/mm³
  • Hemoglobin > 10 g/dL (in the absence of packed red blood cell transfusions within the past 4 weeks)
  • Creatinine < 2 mg/dL
  • AST and ALT < 2 times upper limit of normal (ULN)
  • Alkaline phosphatase < 2 times ULN
  • Fertile patients must use effective double-method contraception during and for 1 month after completion of study treatment
  • 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

    • Patients with chronic, stable radiographic changes who are asymptomatic are eligible


  • See Disease Characteristics
  • At 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

    • The irradiated lesion must not be used to assess response rate
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00483561

United States, Nebraska
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-6805
Sponsors and Collaborators
University of Nebraska
National Cancer Institute (NCI)
Principal Investigator: Ralph Hauke, MD University of Nebraska
Principal Investigator: Elizabeth C. Reed, MD University of Nebraska

Responsible Party: Elizabeth Reed, MD, Principal Investigator, University of Nebraska Identifier: NCT00483561     History of Changes
Other Study ID Numbers: 285-03
P30CA036727 ( U.S. NIH Grant/Contract )
First Posted: June 7, 2007    Key Record Dates
Results First Posted: July 17, 2018
Last Update Posted: December 18, 2018
Last Verified: November 2018

Keywords provided by Elizabeth Reed, MD, University of Nebraska:
adenocarcinoma of the prostate
recurrent prostate cancer
stage III prostate cancer
stage IV prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Etoposide phosphate
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors