Combination Chemotherapy as First-Line Therapy in Treating Patients With Locally Advanced or Metastatic Neuroendocrine Tumors of the Duodenum or Pancreas That Cannot Be Removed By Surgery

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as fluorouracil, leucovorin, and irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. PURPOSE: This phase II trial is studying how well combination chemotherapy works as first-line therapy in treating patients with locally advanced or metastatic neuroendocrine tumors of the duodenum or pancreas that cannot be removed by surgery.

Detailed Description
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OBJECTIVES: Primary Determine the 6-month progression-free survival rate in patients with unresectable locally advanced or metastatic neuroendocrine tumors of the duodenum/pancreas treated with fluorouracil, leucovorin calcium, and irinotecan hydrochloride as first-line chemotherapy. Secondary Determine tumor and biologic response at 6, 12, 18, and 24 months in patients treated with this regimen. Determine the duration of response of the primary tumor in patients treated with this regimen. Determine the tolerability of this regimen in these patients. Determine the progression-free survival of patients treated with this regimen. Determine the overall survival of patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive irinotecan hydrochloride IV over 90 minutes and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours on days 1 and 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed every 3 months for 1 year and then every 6 months thereafter. PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Official Title
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Study of First-Line Therapy Comprising Leucovorin Calcium, Fluorouracil, and Irinotecan (FOLFIRI) in Patients With Progressive Locally Advanced or Metastatic Duodenal-Pancreatic Endocrine Tumors

Conditions
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Gastrointestinal Carcinoid Tumor, Islet Cell Tumor, Neoplastic Syndrome

Intervention / Treatment
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* Drug: fluorouracil
* Drug: irinotecan hydrochloride
* Drug: leucovorin calcium


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of neuroendocrine tumor of the duodenum/pancreas by histology or bone scan Functional or nonfunctional tumor Tumor meets ≥ 1 of the following criteria: Hepatic or extrahepatic metastases Progressive locally advanced tumor (primary or adenopathies) Unresectable disease Tumor differentiated and meets the following criteria: Ki 67 ≤ 15% Less than 10 mitoses per 10 large fields Measurable or evaluable disease Target lesions must meet 1 of the following criteria within the past 6 months: Increase of 20% in the longest diameter New metastases detected Minimum size of lesions must be 1 of the following: More than 15 mm for metastases More than 50 mm for primary tumor or local lymph nodes PATIENT CHARACTERISTICS: WHO performance status 0-2 Creatinine ≤ 1.5 mg/dL Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Bilirubin ≤ 1.8 mg/dL No coronary insufficiency or symptomatic cardiac disease No intestinal obstruction, enteropathy, or uncontrolled chronic diarrhea No Gilbert's disease No psychological, social, familial, or geographic condition that would preclude study treatment Not pregnant or nursing Fertile patients must use effective contraception during and for 6 months after completion of study therapy No other condition that would preclude study therapy PRIOR CONCURRENT THERAPY: No prior adjuvant radiotherapy At least 3 months since prior interferon Prior somatostatin analogs or antisecretories allowed No other prior treatment for this cancer No concurrent radiotherapy to the target lesion

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FOLFIRI<br> | Drug: fluorouracil<br> <br> Drug: irinotecan hydrochloride<br> <br> Drug: leucovorin calcium<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gastrinoma, metastatic gastrointestinal carcinoid tumor, recurrent gastrointestinal carcinoid tumor, regional gastrointestinal carcinoid tumor, insulinoma, WDHA syndrome, glucagonoma, pancreatic polypeptide tumor, somatostatinoma, recurrent islet cell carcinoma