GastrinomaPhase 2NCT00075439
Gefitinib in Treating Patients With Progressive Metastatic Neuroendocrine Tumors
A Phase 2 study testing gefitinib and laboratory biomarker analysis in people with Gastrinoma and Glucagonoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastrinoma, Glucagonoma, Insulinoma
- What is being tested?
- gefitinib and laboratory biomarker analysis
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2003to May 2007
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%
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- ≥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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Trial of ZD1839 (Iressa®) in Metastatic Neuroendocrine Tumors
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.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the 6 month progression free survival rate in patients with progressive, advanced neuroendocrine tumors treated with ZD1839.
SECONDARY OBJECTIVES:
- 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.
- Conditions
- Gastrinoma, Glucagonoma, Insulinoma, Metastatic Gastrointestinal Carcinoid Tumor, Pancreatic Polypeptide Tumor, Recurrent Gastrointestinal Carcinoid Tumor
- Being tested
- gefitinib, laboratory biomarker analysis
- Medical subject headings
- Gastrinoma, Glucagonoma, Insulinoma, Carcinoma, Islet Cell, Somatostatinoma, Vipoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
gefitinibDrug
Also called Iressa, ZD 1839
Given orally
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | Patients receive oral gefitinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: gefitinib; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients progression-free 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.
Measured: At 6 months
Secondary outcomes (6)
Incidence of adverse events graded according to NCI CTCAE version 3.0
The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.
Measured: 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
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.
Measured: Up to 2 years
Survival time
The distribution of survival time will be estimated using the method of Kaplan-Meier.
Measured: Time from registration to death due to any cause, assessed up to 2 years
Time to disease progression
The distribution of time to progression will be estimated using the method of Kaplan-Meier.
Measured: Time from randomization to documentation of disease progression, assessed up to 2 years
Duration of response
This data will be descriptively summarized and graphically evaluated.
Measured: 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
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2004 (estimated)
- Study startDec 2003
- Primary completionMay 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GastrinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Timothy Hobday, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00075439
- Sponsor's protocol ID
- NCI-2012-02796
- Other IDs
- MC0279, N01CM62205
- Status last verified
- Jun 2013
- First submitted
- 9 Jan 2004
- Last updated
- 4 Jun 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of ZD1839 (Iressa®) in Metastatic Neuroendocrine Tumors
- ClinicalTrials.gov ID
- NCT00075439
- Acronym / sponsor ID
- NCI-2012-02796
- Conditions
- Gastrinoma, Glucagonoma, Insulinoma, Metastatic Gastrointestinal Carcinoid Tumor, Pancreatic Polypeptide Tumor, Recurrent Gastrointestinal Carcinoid Tumor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Dec 2003
- Primary completion
- May 2007 (actual)
- First posted
- 12 Jan 2004 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To determine the 6 month progression free survival rate in patients with progressive, advanced neuroendocrine tumors treated with ZD1839.
SECONDARY OBJECTIVES:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: gefitinib, Other: laboratory biomarker analysisPatients receive oral gefitinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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:
- ≥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
Key exclusion criteria (33 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| gefitinibAlso: Iressa, ZD 1839Given orally | Drug | Arm I |
| laboratory biomarker analysisCorrelative studies | Other | Arm I |
Primary outcome
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.
6 secondary outcomes
Incidence of adverse events graded according to NCI CTCAE version 3.0
Time frame: 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
Time frame: Up to 2 years
Survival time
Time frame: Time from registration to death due to any cause, assessed up to 2 years
Time to disease progression
Time frame: Time from randomization to documentation of disease progression, assessed up to 2 years
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2013.
Related trials for Gastrinoma
Active, not recruitingObservational study
DOTATOC PET/CT for Imaging NET Patients
Neuroendocrine Tumors, Insulinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Timothy Hobday principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing gefitinib and laboratory biomarker analysis in people with Gastrinoma and Glucagonoma, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients progression-free at 6 months (time frame: At 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2013.