Status and phase
Conditions
Treatments
Study type
Funder types
Identifiers
About
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 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.
Enrollment
Sex
Ages
Volunteers
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:
≥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
PLT ≥ 75,000/ mm3
Hgb ≥ 8.0 g/dL
Total bilirubin ≤ 2 x upper normal limit (UNL)
Alkaline phosphatase ≤ 3 x UNL (5 x UNL if liver metastases present)
AST ≤ 3 x UNL (≤ 5 x UNL if liver metastases present)
Creatinine ≤ 1.5 x UNL
ECOG performance score (ps) ≤ 2
Life expectancy ≥ 24 weeks
Capable of understanding the investigational nature, potential risks and benefits of the study and able to provide valid informed consent
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:
Anaplastic or high-grade histology
Any of the following prior therapies:
Concurrent chemotherapy or radiation therapy
Any of the following:
Known abnormality of cornea, such as:
Uncontrolled intercurrent illness including, but not limited to:
Known brain metastases; Note: These patients are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
Known HIV-positive patients receiving combination anti-retroviral therapy; Note: These patients are excluded from the study because of possible pharmacokinetic interactions with ZD1839 and because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination and anti-retroviral therapy when indicated
Concurrent or recent use (≤ 7 days prior to ZD1839 administration) of phenytoin, carbamazepine, barbiturates, rifampicin, oxcarbazepine, rifapentine, modafinil, or St. John's Wort; Note: Because these drugs induce CYP3A4 enzymes and can cause reductions in ZD1839 plasma concentrations below levels thought to be biologically active, patients with concurrent or recent use of these drugs are excluded from the study
History of other invasive malignancy ≤ the previous 3 years, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix
Primary purpose
Allocation
Interventional model
Masking
90 participants in 1 patient group
Loading...
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal