This phase II trial is studying how well gefitinib works in treating patients with progressive metastatic neuroendocrine tumors. Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.
Full Title of Study: “A Phase II Trial of ZD1839 (Iressa®) in Metastatic Neuroendocrine Tumors”
- Study Type: Interventional
- Study Design
- Allocation: N/A
- Intervention Model: Single Group Assignment
- Primary Purpose: Treatment
- Masking: None (Open Label)
- Study Primary Completion Date: May 2007
PRIMARY OBJECTIVES: I. To determine the 6 month progression free survival rate in patients with progressive, advanced neuroendocrine tumors treated with ZD1839. SECONDARY OBJECTIVES: I. Objective tumor response rate. II. Progression free survival and time to progression. III. Improvement in circulating hormone levels. IV. Overall survival V. We will explore the molecular characterization of these tumors in attempt to understand the role of EGFR expression and its inhibition with ZD1839 in neuroendocrine tumors. The measurements will be performed on pretreatment and post-treatment tumor biopsies when possible: EGFR expression and gene amplification (IHC for EGFR and phosphorylated EGFR, ISH for gene amplification); Activation of the Ras/Raf/MAPK pathway (IHC for phosphorylated MAPK); Cell proliferation (Ki-67 staining); Apoptosis (TUNEL assay). OUTLINE: This is a multicenter study. Patients are stratified according to disease type (carcinoid vs islet cell and other neuroendocrine tumors). Patients receive oral gefitinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months until disease progression and then every 6 months for up to 2 years from study entry.
- Drug: gefitinib
- Given orally
- Other: laboratory biomarker analysis
- Correlative studies
Arms, Groups and Cohorts
- Experimental: Arm I
- Patients receive oral gefitinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Clinical Trial Outcome Measures
- Proportion of patients progression-free at 6 months
- Time Frame: At 6 months
- If patients are lost to follow-up or discontinue active monitoring prior to 6 months post-registration, we will consider censoring them for the evaluation of the primary endpoint. Here, Kaplan-Meier methodology will be used to estimate the final success proportion (ie, 6 month success rate with a 95% confidence interval). Otherwise, ninety-five percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.
- Incidence of adverse events graded according to NCI CTCAE version 3.0
- Time Frame: Up to 2 years
- The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.
- Confirmed tumor response to treatment will be evaluated and will be considered a PR or CR on consecutive evaluations at least 4 weeks apart
- Time Frame: Up to 2 years
- The proportion of responses will be evaluated and will be tabulated. Assuming a binomial distribution for the incidence of response, 95% confidence intervals will also be generated.
- Survival time
- Time Frame: Time from registration to death due to any cause, assessed up to 2 years
- The distribution of survival time will be estimated using the method of Kaplan-Meier.
- Time to disease progression
- Time Frame: Time from randomization to documentation of disease progression, assessed up to 2 years
- The distribution of time to progression will be estimated using the method of Kaplan-Meier.
- Duration of response
- Time Frame: Date from which the patient’s objective status is first noted to be either a CR or PR to the date progression is documented, assessed up to 2 years
- This data will be descriptively summarized and graphically evaluated.
- Time to treatment failure
- Time Frame: Time from the date of registration to the date at which the patient is removed from treatment due to progression, toxicity, refusal, or death, assessed up to 2 years
Participating in This Clinical Trial
Gender Eligibility: All
Minimum Age: 18 Years
Maximum Age: N/A
Are Healthy Volunteers Accepted: No
- Lead Sponsor
- National Cancer Institute (NCI)
- Provider of Information About this Clinical Study
- Overall Official(s)
- Timothy Hobday, Principal Investigator, Mayo Clinic
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