Clinical Trial: AMG 706 and Octreotide in Treating Patients With Low-Grade Neuroendocrine Tumors

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase II Clinical and Biologic Study of AMG 706 and Octreotide in Patients With Low-Grade Neuroendocrine Tumors

Brief 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.

Detailed Summary:

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 computerized tomography (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 achaete-scute homolog-1 (hASH1), 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 VEGF levels. Gene expression of downstream markers of Raf kinase expression (raf, MEK, and ERK) as well as hASH1 an
Sponsor: Eastern Cooperative Oncology Group

Current Primary Outcome: Four-month Progression-free Survival Rate [ Time Frame: assessed every 4 weeks while on treatment and at three months post-treatment for participants treated for one cycle, up to month four ]

Original Primary Outcome:

• Time to progression
• Progression-free survival at 4 months

Current Secondary Outcome:

• Overall Survival [ Time Frame: assessed every 3 months if patient is < 2 years from study entry, then every 6 months up to 5 years ]
  Overall survival (OS) is defined as the time from registration until death (event), or censored at last date known alive. OS was estimated using the Kaplan-Meier method , with 95% confidence intervals calculated using Greenwood's formula
• Objective Response Rate [ Time Frame: assessed every 8 weeks while on treatment, and frequency of tumor measurements during follow-up were determined by the treating physician, assessed up to 5 years ]
  Tumor response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Objective response rate is defined as number of patients with complete response (CR) or partial response (PR) divided by the total number of analyzable patients. CR is defined as complete disappearance of all tumor lesions, and partial response is defined as at least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum longest diameter.

Original Secondary Outcome:

• Objective response (complete or partial response, progressive disease, or stable disease) as measured by RECIST criteria
• Toxicity and tolerability
• Effect of AMG 706 on markers in tumor cells, including VEGF, VEGFR-2, chromogranin A, human achaetescute homolog-1, and Notch1

Dates:
Date Received: January 25, 2007
Date Started: September 2008
Date Completion:
Last Updated: July 12, 2016
Last Verified: July 2016