Gefitinib in Treating Patients With Progressive Metastatic Neuroendocrine Tumors

Official Title: “A Phase II Trial Of ZD1839 (Iressa) In Metastatic Neuroendocrine Tumors”

RATIONALE: Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

PURPOSE: This phase II trial is studying how well gefitinib works in treating patients with progressive metastatic neuroendocrine tumors.

OBJECTIVES:

Primary - Determine the 6-month progression-free survival rate in patients with progressive metastatic neuroendocrine tumors treated with gefitinib.

Secondary - Determine the objective tumor response rate in patients treated with this drug. - Determine time to progression and progression-free and overall survival in patients treated with this drug. - Determine improvement in circulating hormone levels in patients treated with this drug.

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.

PROJECTED ACCRUAL: A total of 34-90 patients (22-51 for carcinoid stratum and 12-39 for islet cell/other neuroendocrine tumor stratum) will be accrued for this study within 9 months.

Intervention(s) in this Clinical Trial

• Drug: gefitinib

Primary Measures

• Proportion of successes
  • Safety Issue?: No

Secondary Measures

• Toxicity as assessed by NCI CTCAE v3.0
  • Safety Issue?: Yes
• Confirmed tumor response (partial and complete)
  • Safety Issue?: No
• Survival
  • Safety Issue?: No
• Time to disease progression
  • Safety Issue?: No
• Duration of response
  • Safety Issue?: No
• Time to treatment failure
  • Safety Issue?: No

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic neuroendocrine neoplasm OR primary neuroendocrine tumor with clear clinical evidence of metastases
• No anaplastic or high-grade histology
• Measurable disease
• Radiographic evidence of disease progression within the past 60 weeks after prior systemic therapy, chemoembolization, embolization, or observation and defined as 1 of the following:
• 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%
• No thyroid carcinoma of any histology or pheochromocytoma/paraganglioma
• No known brain metastases

PATIENT CHARACTERISTICS:

• Age
• 18 and over
• Performance status
• ECOG 0-2
• Life expectancy
• At least 24 weeks
• Hematopoietic
• Absolute neutrophil count at least 1,000/mm^3
• Platelet count at least 75,000/mm^3
• Hemoglobin at least 8.0 g/dL
• Hepatic
• Bilirubin no greater than 2 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 3 times ULN*
• AST no greater than 3 times ULN* NOTE: *5 times ULN if liver metastases are present
• Renal
• Creatinine no greater than 1.5 times ULN
• Cardiovascular
• No symptoms of congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• Gastrointestinal
• No gastrointestinal tract disease resulting in an inability to take oral medication (e.g., dysphagia or inability to swallow capsules intact)
• No requirement for IV alimentation
• No active peptic ulcer disease
• Ophthalmic
• No known abnormality of the cornea, such as any of the following:
• History of dry eye syndrome or Sjögren's syndrome
• Congenital abnormality
• Abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-rose)
• Abnormal corneal sensitivity test (e.g., Schirmer test)
• Other
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No other uncontrolled illness
• No other invasive malignancy within the past 3 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

• Biologic therapy
• At least 4 weeks since prior interferon injection
• Chemotherapy
• At least 4 weeks since prior chemotherapy
• No more than 1 prior systemic chemotherapy regimen
• Chemoembolization is not considered systemic chemotherapy
• No concurrent chemotherapy
• Endocrine therapy
• At least 2 weeks since prior short-acting octreotide injection (6 weeks for long-acting injection)
• Concurrent octreotide allowed provided a stable dose has been administered for at least 1 month and there is documented tumor progression on the current dose with no plan for increasing the dose
• Radiotherapy
• At least 3 weeks since prior radiotherapy
• No concurrent radiotherapy
• Surgery
• At least 4 weeks since prior major surgery
• Other
• Recovered from prior therapy
• At least 4 weeks since other prior systemic therapy
• At least 4 weeks since prior hepatic artery embolization/chemoembolization
• More than 7 days since prior administration of the following CYP3A4 inducers:
• Phenytoin
• Carbamazepine
• Barbiturates
• Rifampin
• Oxcarbazepine
• Rifapentine
• Modafinil
• Hypericum perforatum (St. John's wort)
• No prior procedures adversely affecting intestinal absorption
• No prior epidermal growth factor-targeted regimens (e.g., erlotinib, EKB-569, or gefitinib)
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational treatment
• No concurrent CYP3A4 inducers

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Mayo Clinic Other

Overall Clinical Trial Officials and Contacts

Timothy Hobday, MD Study Chair Mayo Clinic  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00075439

Study ID Number: CDR0000346420

ClinicalTrials.gov Identifier: NCT00075439

Health Authority: United States: Food and Drug Administration

Clinical trial summary from the National Cancer Institute's PDQ® database