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

Brief summary public domain (ClinicalTrials.gov)

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 description public domain (ClinicalTrials.gov)

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 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.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Four-month Progression-free Survival Rate [assessed every 4 weeks while on treatment and at three months post-treatment for participants treated for one cycle, up to month four]. Number, percentage of participants (90% Confidence Interval). AMG 706+Octreotide (n=42): 78.5 (65.6 to 88.3). Analysis, AMG 706+Octreotide: p=<0.001; one sample binomial test; superiority or other legacy.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Overall Survival [assessed every 3 months if patient is < 2 years from study entry, then every 6 months up to 5 years]. Median, months (95% Confidence Interval). AMG 706+Octreotide (n=44): 27.5 (14.6 to 45.1).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Objective Response Rate [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]. Number, percentage of participants (90% Confidence Interval). AMG 706+Octreotide (n=44): 13.6 (6 to 25).