Clinical trial NCT00427349
Conditions: Gastrointestinal Carcinoid Tumor Islet Cell Tumor Neoplastic Syndrome
Keywords: localized gastrointestinal carcinoid tumor recurrent gastrointestinal carcinoid tumor metastatic gastrointestinal carcinoid tumor regional gastrointestinal carcinoid tumor gastrinoma insulinoma WDHA syndrome glucagonoma pancreatic polypeptide tumor somatostatinoma recurrent islet cell carcinoma neuroendocrine tumor
Sponsor: Eastern Cooperative Oncology Group
Start date: 2008-11-07; Completion date: 2015-04-01
Enrollment: 46 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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 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 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.

Arms: arm 1: Patients receive oral AMG 706 and octreotide acetate intramuscularly (IM) once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

AMG 706 was administered on a flat scale of mg/day and not by weight or body surface area (BSA). AMG 706 was provided as a 25 mg tablet; the daily dose was 125 mg administered as five 25 mg tablets in the morning. AMG 706 was taken daily without breaks in treatment.

One dose consisted of octreotide-LAR 30 mg administered IM on day 1 of each cycle. The first octreotide-LAR injection would correspond with the first day of AMG 706 and then on day 1 of subsequent cycles.
Interventions: intervention 1: AMG 706 intervention 2: octreotide
Intervention descriptions: intervention 1: AMG 706 was administered on a flat scale of mg/day and not by weight or body surface area (BSA). AMG 706 was provided as a 25 mg tablet; the daily dose was 125 mg administered as five 25 mg tablets in the AM. AMG 706 was taken daily without breaks in treatment intervention 2: One dose consisted of octreotide-LAR 30 mg administered IM on day 1 of each cycle. The first octreotide-LAR injection would correspond with the first day of AMG 706 and then on day 1 of subsequent cycles.

Protocol documents: