Know Cancer

forgot password

A Phase II Trial of ZD1839 (Iressa®) in Metastatic Neuroendocrine Tumors

Phase 2
18 Years
Not Enrolling
Gastrinoma, Glucagonoma, Insulinoma, Metastatic Gastrointestinal Carcinoid Tumor, Pancreatic Polypeptide Tumor, Recurrent Gastrointestinal Carcinoid Tumor, Recurrent Islet Cell Carcinoma, Somatostatinoma, WDHA Syndrome

Thank you

Trial Information

A Phase II Trial of ZD1839 (Iressa®) in Metastatic Neuroendocrine Tumors


I. To determine the 6 month progression free survival rate in patients with progressive,
advanced neuroendocrine tumors treated with ZD1839.


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.

Inclusion Criteria:

- Histologically confirmed metastatic neuroendocrine neoplasms or histologic
confirmation of primary neuroendocrine tumor with clear clinical evidence of

- 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

- 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

- 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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Proportion of patients progression-free at 6 months

Outcome Description:

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.

Outcome Time Frame:

At 6 months

Safety Issue:


Principal Investigator

Timothy Hobday

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic


United States: Food and Drug Administration

Study ID:




Start Date:

December 2003

Completion Date:

Related Keywords:

  • Gastrinoma
  • Glucagonoma
  • Insulinoma
  • Metastatic Gastrointestinal Carcinoid Tumor
  • Pancreatic Polypeptide Tumor
  • Recurrent Gastrointestinal Carcinoid Tumor
  • Recurrent Islet Cell Carcinoma
  • Somatostatinoma
  • WDHA Syndrome
  • Carcinoid Tumor
  • Carcinoma
  • Gastrinoma
  • Zollinger-Ellison Syndrome
  • Glucagonoma
  • Insulinoma
  • Somatostatinoma
  • Neuroendocrine Tumors
  • Malignant Carcinoid Syndrome
  • Gastrointestinal Neoplasms
  • Carcinoma, Islet Cell



Mayo Clinic Rochester, Minnesota  55905