Overview

This trial is active, not recruiting.

Conditions gastrointestinal carcinoid tumor, islet cell tumor, neoplastic syndrome
Treatments motesanib diphosphate, octreotide acetate, gene expression analysis, protein expression analysis, reverse transcriptase-polymerase chain reaction, laboratory biomarker analysis, computed tomography
Phase phase 2
Sponsor Eastern Cooperative Oncology Group
Collaborator National Cancer Institute (NCI)
Start date September 2008
End date November 2012
Trial size 44 participants
Trial identifier NCT00427349, CDR0000526256, ECOG-E4206

Summary

RATIONALE: AMG 706 and octreotide may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well AMG 706 and octreotide work in treating patients with low-grade neuroendocrine tumors.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Masking open label
Primary purpose treatment

Primary Outcomes

Measure
Time to progression
time frame:
Progression-free survival at 4 months
time frame:

Secondary Outcomes

Measure
Objective response (complete or partial response, progressive disease, or stable disease) as measured by RECIST criteria
time frame:
Toxicity and tolerability
time frame:
Effect of AMG 706 on markers in tumor cells
time frame:

Eligibility Criteria

Male or female participants at least 18 years old.

DISEASE CHARACTERISTICS: - Histologically confirmed low-grade neuroendocrine neoplasm - Measurable disease - Radiographic evidence of disease progression after any prior systemic therapy, chemoembolization, bland embolization, or observation, defined by either of the following: - Appearance of a new lesion - At least 20% increase in the longest diameter of any previously documented lesion or in the sum of the longest diameters of multiple lesions - Tissue block from original diagnostic or surgical specimen required - Concurrent stable-dose octreotide acetate required - No small cell lung cancer, medullary thyroid cancer, paraganglioma, or pheochromocytoma PATIENT CHARACTERISTICS: - ECOG performance status 0-2 - 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 reactions to AMG 706 or derivatives or to octreotide acetate injections - No gastrointestinal tract disease resulting in an inability to take oral medication (i.e., ulcerative disease, uncontrolled nausea, vomiting, or diarrhea, bowel obstruction, or inability to swallow tablets) - No requirement for IV alimentation - Absolute neutrophil count ≥ 1,000/mm³ - Platelet count ≥ 75,000/mm³ - Hemoglobin level ≥ 8.0 g/dL - Bilirubin ≤ 2.0 times upper limit of normal (ULN) - AST ≤ 3 times ULN (5 times ULN if liver metastases are present) - LVEF ≥ institutional lower limit of normal as evaluated by echocardiography or MUGA scan - No history of uncontrolled hypertension (resting blood pressure > 150/90 mm Hg) - Antihypertensive medications allowed if patients is stable on their current dose - No history of the following within the past 12 months: - New York Heart Association class III or IV congestive heart failure - Unstable angina pectoris - Myocardial infarction - Symptomatic cardiac arrhythmia - Cerebrovascular accident or transient ischemic attack - No history of arterial or venous thrombosis within the past 12 months PRIOR CONCURRENT THERAPY: - See Disease Characteristics - One prior systemic chemotherapy regimen for low-grade neuroendocrine neoplasm allowed - Chemoembolization is not considered systemic chemotherapy - At least 4 weeks since prior major surgery, chemotherapy, radiation therapy, other systemic therapy, or local liver therapy - No prior procedures that would adversely affect intestinal absorption - No prior anti-vascular endothelial growth factors - No concurrent chemotherapy or radiation therapy

Additional Information

Official title A Phase II Clinical and Biologic Study of AMG 706 and Octreotide in Patients With Low-Grade Neuroendocrine Tumors
Description OBJECTIVES: Primary - Determine the 4-month progression-free survival (PFS) of patients with low-grade neuroendocrine tumors treated with AMG 706 and octreotide acetate. Secondary - Determine the response rate and overall survival of patients treated with these drugs. - Determine the toxicity and tolerability of AMG 706 in these patients. - Determine the effect of AMG 706 on tumor perfusion by functional CT scan. - Determine the effect of AMG 706 on tumor markers (e.g., chromogranin A, 5-hydroxyindoleacetic acid, and gastrin) specific for neuroendocrine tumors. - Determine the effect of AMG 706 on serum vascular endothelial growth factor (VEGF) levels. - Determine the expression of VEGF, VEGF receptor-2 (VEGFR-2), chromogranin A, human achaetescute homolog-1, and Notch1 markers of neuroendocrine tumors. OUTLINE: This is a multicenter study. Patients receive oral AMG 706 and octreotide acetate intramuscularly once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Plasma samples are collected at baseline, periodically during study treatment, and at 4 weeks after the completion of study treatment. Samples are used to determine plasma vascular endothelial growth factor (VEGF) levels. Gene expression of downstream markers of Raf kinase expression (raf, MEK, and ERK) as well as HASH1 and Notch1 are evaluated at baseline. Tumor tissue collected at diagnosis or prior surgery is examined by reverse transcriptase-polymerase chain reaction assay. Contrast CT scans are conducted at baseline, day 2 of course 1, and week 8 to assess tumor perfusion. After the completion of study treatment, patients are followed periodically for 5 years. PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study.
Trial information was received from ClinicalTrials.gov and was last updated in July 2012.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).