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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by:
University of Nebraska
ClinicalTrials.gov Identifier:
NCT00483561
First received: June 6, 2007
Last updated: March 8, 2011
Last verified: March 2011

June 6, 2007
March 8, 2011
January 2004
December 2014   (final data collection date for primary outcome measure)
Overall response rate as measured by RECIST criteria [ Time Frame: After 14 patients are enrolled ] [ Designated as safety issue: No ]
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 as measured by RECIST criteria
Complete list of historical versions of study NCT00483561 on ClinicalTrials.gov Archive Site
  • Adverse events and toxicities as assessed by NCI CTC v2.0 [ Time Frame: When reported by patients, and at physical evaluations ] [ Designated as safety issue: Yes ]
  • Laboratory values [ Time Frame: At every cycle ] [ Designated as safety issue: No ]
  • Biomarkers [ Time Frame: At every cycle ] [ Designated as safety issue: No ]
  • Adverse events and toxicities as assessed by NCI CTC v2.0
  • Laboratory values
  • Biomarkers
Not Provided
Not Provided
 
Gefitinib and Etoposide in Treating Patients With Advanced Prostate Cancer That Did Not Respond to Hormone Therapy
A Phase II Study Evaluating the Efficacy of Iressa Plus Etoposide in Patients With Advanced Hormone Refractory Prostate Cancer

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.

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.

Interventional
Phase 2
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Prostate Cancer
  • Drug: etoposide
    250 mg p.o. daily, starting on Day 1and taken on a continuous basis throughout the trial.
  • Drug: 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: laboratory biomarker analysis
    The blood samples will be obtained in EDTA tubes, spun down, and the serum removed and stored at 80 degrees C in small aliquots for later use. When we have sufficient samples to use a kit, they will be thawed and sampled for the various biomarkers using ELISA kits from R&D Technology (Seattle). The antiEGFR antibodies will also be determined by using ELISA, but with kits prepared within our institution.
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
21
Not Provided
December 2014   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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

PRIOR CONCURRENT THERAPY:

  • 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
Male
19 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00483561
285-03, P30CA036727, UNMC-28503, ZENECA-UNMC-28503
Yes
Elizabeth C. Reed, UNMC Eppley Cancer Center at the University of Nebraska Medical Center
University of Nebraska
National Cancer Institute (NCI)
Principal Investigator: Ralph Hauke, MD University of Nebraska
Principal Investigator: Elizabeth C. Reed, MD University of Nebraska
University of Nebraska
March 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP