- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT00075439
Gefitinib in Treating Patients With Progressive Metastatic Neuroendocrine Tumors
A Phase II Trial of ZD1839 (Iressa®) in Metastatic Neuroendocrine Tumors
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
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.
Undersøgelsestype
Tilmelding (Forventet)
Fase
- Fase 2
Kontakter og lokationer
Studiesteder
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Minnesota
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Rochester, Minnesota, Forenede Stater, 55905
- Mayo Clinic
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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
- 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:
- 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)
- < 4 weeks from last Interferon injection
- < 2 weeks from last octreatide short acting injection or < 6 weeks long acting injection; Note: concurrent octreatide allowed if stable dose has been administered for ≥1 month, there is documented tumor progression on the current dose, and there is no current plan for increasing dose • Other concurrent treatment considered investigational
- Concurrent chemotherapy or radiation therapy
Any of the following:
- Gastrointestinal tract disease resulting in an inability to take oral medication (e.g. dysphagia or inability to swallow capsules intact).
- Requirement for IV alimentation
- Prior procedures clearly adversely affecting intestinal absorption
- Active peptic ulcer disease
- Failure to fully recover from adverse effects of prior therapies regardless of interval since last treatment
Known abnormality of cornea, such as:
- History of dry eye syndrome or Sjogren syndrome
- Congenital abnormality
- Abnormal slit-lamp examination using a vital dye (e.g.: fluorescein or Bengal-rose)
- Abnormal corneal sensitivity test (Schirmer test)
Uncontrolled intercurrent illness including, but not limited to:
- Ongoing or active infection
- Symptoms of congestive heart failure
- Unstable angina pectoris, cardiac arrhythmia
- Psychiatric illness/social situation that would limit compliance with study requirement
- 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
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: N/A
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
---|---|
Eksperimentel: 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.
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Korrelative undersøgelser
Gives oralt
Andre navne:
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Proportion of patients progression-free at 6 months
Tidsramme: 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.
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At 6 months
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Incidence of adverse events graded according to NCI CTCAE version 3.0
Tidsramme: Up to 2 years
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The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.
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Up to 2 years
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Confirmed tumor response to treatment will be evaluated and will be considered a PR or CR on consecutive evaluations at least 4 weeks apart
Tidsramme: Up to 2 years
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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.
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Up to 2 years
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Survival time
Tidsramme: Time from registration to death due to any cause, assessed up to 2 years
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The distribution of survival time will be estimated using the method of Kaplan-Meier.
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Time from registration to death due to any cause, assessed up to 2 years
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Time to disease progression
Tidsramme: Time from randomization to documentation of disease progression, assessed up to 2 years
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The distribution of time to progression will be estimated using the method of Kaplan-Meier.
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Time from randomization to documentation of disease progression, assessed up to 2 years
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Duration of response
Tidsramme: 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
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This data will be descriptively summarized and graphically evaluated.
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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
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Time to treatment failure
Tidsramme: 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
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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
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Samarbejdspartnere og efterforskere
Sponsor
Efterforskere
- Ledende efterforsker: Timothy Hobday, Mayo Clinic
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Faktiske)
Studieafslutning
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Sygdomme i fordøjelsessystemet
- Patologiske processer
- Neoplasmer efter histologisk type
- Neoplasmer efter sted
- Adenocarcinom
- Karcinom
- Neoplasmer, kirtel og epitel
- Sygdomme i det endokrine system
- Sygdomsegenskaber
- Neoplasmer i fordøjelsessystemet
- Gastrointestinale sygdomme
- Neoplasmer i endokrine kirtler
- Neuroektodermale tumorer
- Neoplasmer, kimceller og embryonale
- Neoplasmer, nervevæv
- Pancreassygdomme
- Adenom
- Karcinom, neuroendokrin
- Bugspytkirtel neoplasmer
- Adenom, øcelle
- Neoplasmer
- Tilbagevenden
- Gastrointestinale neoplasmer
- Neuroendokrine tumorer
- Carcinoid tumor
- Malignt carcinoid syndrom
- Karcinom, øcelle
- Insulinom
- Gastrinom
- Glukagonom
- Somatostatinom
- Vipoma
- Molekylære mekanismer for farmakologisk virkning
- Enzymhæmmere
- Antineoplastiske midler
- Proteinkinasehæmmere
- Gefitinib
Andre undersøgelses-id-numre
- NCI-2012-02796
- N01CM62205 (U.S. NIH-bevilling/kontrakt)
- MC0279
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
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produkt fremstillet i og eksporteret fra U.S.A.
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