Clinical trial NCT00483561: Gefitinib and Etoposide in Treating Patients With Advanced Prostate Cancer That Did Not Respond to Hormone Therapy
Official title: A Phase II Study Evaluating the Efficacy of Iressa Plus Etoposide in Patients With Advanced Hormone Refractory Prostate Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: adenocarcinoma of the prostate
recurrent prostate cancer
stage III prostate cancer
stage IV prostate cancer
Lead sponsor: University of Nebraska
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-06-07
Enrollment: 26
Sex: MALE
Minimum age (years): 19
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall Response Rate as Measured by RECIST Criteria and PSA Criteria
timeFrame: Approximately 3 years
Secondary outcomes:
measure: Biomarkers
timeFrame: At every cycle
Other outcomes:
Locations:
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
Study officials:
affiliation: University of Nebraska
name: Ralph Hauke, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Nebraska
name: Elizabeth C Reed, MD
role: PRINCIPAL_INVESTIGATOR
References: