Vatalanib and Octreotide in Treating Patients With Progressive Neuroendocrine Tumors

Study Overview
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Brief Summary
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RATIONALE: Vatalanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by stopping blood flow to the tumor. Octreotide may help control symptoms, such as diarrhea, caused by the tumor. Giving vatalanib together with octreotide may be an effective treatment for neuroendocrine tumors. PURPOSE: This phase II trial is studying how well giving vatalanib together with octreotide works in treating patients with progressive neuroendocrine tumors.

Detailed Description
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OBJECTIVES: Determine the 4-month progression-free and overall survival of patients with progressive low-grade neuroendocrine tumors treated with vatalanib and octreotide. Determine the response rate in patients treated with this regimen. Determine the effect of this regimen on tumor markers (e.g., chromogranin A, 5-HIAA, and gastrin) in these patients. Determine the toxicity and tolerability of this regimen in these patients. OUTLINE: This is a multicenter study. Patients receive oral vatalanib once daily on days 1- 28 and octreotide* intramuscularly or IV on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. NOTE: *Patients on a stable dose (i.e., no changes in dosage within the past 3 months) of octreotide before study entry remain on their current dose and schedule during study participation; patients who experience hypersensitivity and/or toxicity to octreotide may receive vatalanib alone. After completion of study treatment, patients are followed at 4 weeks, every 3 months for 2 years, and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 23-44 patients will be accrued for this study within 3 years.

Official Title
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Phase II Study of Vatalanib and Octreotide in Patients With Progressive Low-Grade Neuroendocrine Tumors

Conditions
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Gastrointestinal Carcinoid Tumor, Islet Cell Carcinoma

Intervention / Treatment
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* Drug: octreotide acetate
* Drug: vatalanib
* Procedure: anti-cytokine therapy
* Procedure: antiangiogenesis therapy
* Procedure: biological therapy
* Procedure: endocrine therapy
* Procedure: enzyme inhibitor therapy
* Procedure: growth factor antagonist therapy
* Procedure: hormone therapy
* Procedure: protein tyrosine kinase inhibitor therapy
* Procedure: somatostatin analogue therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed low-grade neuroendocrine tumors The following tumor types are excluded: Small cell lung cancer Medullary thyroid cancer Paraganglioma Pheochromocytoma Measurable disease Radiographic evidence of disease progression after completion of any prior systemic therapy, chemoembolization, bland embolization, or observation within the past year, defined as either 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 the aggregate of 20% PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic Absolute neutrophil count ≥ 1,000/mm^3 Platelet count ≥ 75,000/mm^3 Hemoglobin ≥ 8.0 g/dL Hepatic Bilirubin ≤ 2.0 times upper limit of normal (ULN) AST ≤ 3 times ULN (5 times ULN if liver metastases are present) Renal Creatinine ≤ 1.5 times ULN Meets 1 of the following criteria: Urine protein negative by dipstick Urine protein:creatinine ratio < 1.0 Urine protein < 1 g by 24-hour urine collection Gastrointestinal Must be able to swallow tablets No ulcerative disease No uncontrolled nausea, vomiting, or diarrhea No bowel obstruction No other gastrointestinal tract disease resulting in an inability to take oral medication Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Must be able to receive a contrast-enhanced CT scan No known history of allergic reaction to vatalanib or its derivatives or octreotide injections PRIOR CONCURRENT THERAPY: Biologic therapy Not specified 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 Not specified Radiotherapy At least 3 weeks since prior radiotherapy No concurrent radiotherapy Surgery At least 4 weeks since prior major surgery Other At least 4 weeks since other prior systemic therapy At least 4 weeks since prior local liver therapy No prior anti-vascular endothelial growth factor agents No concurrent grapefruit or grapefruit juice No concurrent therapeutic warfarin or similar oral anticoagulants that are metabolized by the cytochrome P450 system Concurrent heparin allowed

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: octreotide acetate|nan|
|Drug: vatalanib|nan|
|Procedure: anti-cytokine therapy|nan|
|Procedure: antiangiogenesis therapy|nan|
|Procedure: biological therapy|nan|
|Procedure: endocrine therapy|nan|
|Procedure: enzyme inhibitor therapy|nan|
|Procedure: growth factor antagonist therapy|nan|
|Procedure: hormone therapy|nan|
|Procedure: protein tyrosine kinase inhibitor therapy|nan|
|Procedure: somatostatin analogue therapy|nan|

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, localized gastrointestinal carcinoid tumor, metastatic gastrointestinal carcinoid tumor, recurrent gastrointestinal carcinoid tumor, regional gastrointestinal carcinoid tumor, recurrent islet cell carcinoma, insulinoma, WDHA syndrome, glucagonoma, pancreatic polypeptide tumor, somatostatinoma