A Phase II Trial of ZD1839 (Iressa®) in Metastatic Neuroendocrine Tumors
Overview
- Phase
- Phase 2
- Intervention
- gefitinib
- Conditions
- Gastrinoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 90
- Locations
- 1
- Primary Endpoint
- Proportion of patients progression-free at 6 months
- Status
- Completed
- Last Updated
- 12 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed metastatic neuroendocrine neoplasms or histologic confirmation of primary neuroendocrine tumor with clear clinical evidence of metastases
- •Measurable disease
- •Radiographic evidence of disease progression, following any prior systemic therapy, chemoembolization, embolization, or observation; for eligibility purposes, disease progression will be defined as follows:
- •Either of the following documented by comparison of the on-study radiographic assessment with a prior assessment of the same type performed within the previous 60 calendar weeks:
- •Appearance of a new lesion
- •At least 20% increase in the longest diameter (LD) of any previously documented lesion or an increase in the sum of the LDs of multiple lesions in aggregate of 20%
- •≥4 weeks from the completion of major surgery, chemotherapy or other systemic therapy and hepatic artery embolization/chemoembolization to study registration
- •≥3 weeks from the completion of radiation therapy to study registration
- •Recovered sufficiently from side effects of prior therapy
- •Absolute neutrophil count (ANC) ≥ 1000/mm3
Exclusion Criteria
- •Thyroid carcinoma of any histology or pheochromocytoma/paraganglioma
- •Any of the following as this regimen may be harmful to a developing fetus or nursing child:
- •Pregnant women
- •Breastfeeding women
- •Men or women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device \[IUD\], surgical sterilization, subcutaneous implants, or abstinence, etc.)
- •NOTE: The effects of the agent(s) on the developing human fetus at the recommended therapeutic dose are unknown
- •Anaplastic or high-grade histology
- •Any of the following prior therapies:
- •\> 1 prior systemic chemotherapy regimen (chemoembolization not counted as systemic chemotherapy)
- •Prior EGFR targeted regimen (e.g. OSI-774, EKB-569, ZD1839)
Arms & Interventions
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.
Intervention: gefitinib
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.
Intervention: laboratory biomarker analysis
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Incidence of adverse events graded according to NCI CTCAE version 3.0(Up to 2 years)
- Confirmed tumor response to treatment will be evaluated and will be considered a PR or CR on consecutive evaluations at least 4 weeks apart(Up to 2 years)
- Survival time(Time from registration to death due to any cause, assessed up to 2 years)
- Time to disease progression(Time from randomization to documentation of disease progression, assessed up to 2 years)
- Duration of response(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)
- Time to treatment failure(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)