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

Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00483561
• Other study ID #: 0285-03-FB
• Secondary ID: P30CA036727
• Status: Terminated
• Phase: Phase 2
• Start date: January 2004
• Est. completion date: January 2010

Study information

• Verified date: August 2023
• Source: University of Nebraska
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 26
• Est. completion date: January 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 19 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

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).

Locations

Country	Name	City	State
United States	University of Nebraska Medical Center	Omaha	Nebraska

Sponsors (2)

Lead Sponsor	Collaborator
University of Nebraska	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Biomarkers		At every cycle