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AMG 706 and Octreotide in Treating Patients With Low-Grade Neuroendocrine Tumors
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), January 2009
Sponsors and Collaborators: Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00427349
  Purpose

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.


Condition Intervention Phase
Gastrointestinal Carcinoid Tumor
Islet Cell Tumor
Neoplastic Syndrome
Drug: motesanib diphosphate
Drug: octreotide acetate
Procedure: computed tomography
Procedure: gene expression analysis
Procedure: laboratory biomarker analysis
Procedure: protein expression analysis
Procedure: reverse transcriptase-polymerase chain reaction
Phase II

MedlinePlus related topics: Cancer Carcinoid Tumors
Drug Information available for: Motesanib Octreotide Octreotide acetate
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: A Phase II Clinical and Biologic Study of AMG 706 and Octreotide in Patients With Low-Grade Neuroendocrine Tumors

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Time to progression [ Designated as safety issue: No ]
  • Progression-free survival at 4 months [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective response (complete or partial response, progressive disease, or stable disease) as measured by RECIST criteria [ Designated as safety issue: No ]
  • Toxicity and tolerability [ Designated as safety issue: Yes ]
  • Effect of AMG 706 on markers in tumor cells [ Designated as safety issue: No ]

Estimated Enrollment: 44
Study Start Date: September 2008
Estimated Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
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 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00427349

  Show 63 Study Locations
Sponsors and Collaborators
Eastern Cooperative Oncology Group
Investigators
Study Chair: Kyle D. Holen, MD University of Wisconsin, Madison
Investigator: Mary Mulcahy, MD Robert H. Lurie Cancer Center
Investigator: Peter J. O'Dwyer, MD, BCh University of Pennsylvania
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Study ID Numbers: CDR0000526256, ECOG-E4206
Study First Received: January 25, 2007
Last Updated: January 9, 2009
ClinicalTrials.gov Identifier: NCT00427349  
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
gastrinoma
localized gastrointestinal carcinoid tumor
recurrent gastrointestinal carcinoid tumor
metastatic gastrointestinal carcinoid tumor
regional gastrointestinal carcinoid tumor
insulinoma
WDHA syndrome
glucagonoma
pancreatic polypeptide tumor
somatostatinoma
recurrent islet cell carcinoma

Study placed in the following topic categories:
Gastrointestinal Diseases
Pancreatic Neoplasms
Pancreatic Polypeptide
Octreotide
Neoplasms, Germ Cell and Embryonal
Neuroepithelioma
Endocrine Gland Neoplasms
Digestive System Neoplasms
Carcinoma, Islet Cell
Serotonin Syndrome
Insulinoma
Endocrine System Diseases
Adenoma, Islet Cell
Malignant Carcinoid Syndrome
Carcinoid syndrome
Recurrence
Neuroendocrine Tumors
Carcinoma
Carcinoid tumor
Neuroectodermal Tumors
Gastrinoma
Digestive System Diseases
Gastrointestinal Neoplasms
Pancreatic Diseases
Carcinoid Tumor
Endocrinopathy
Adenocarcinoma
Adenoma
Pancreatic islet cell tumors
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Neoplasms
Neoplasms by Site
Pathologic Processes
Disease
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Syndrome
Neoplasms, Nerve Tissue
Gastrointestinal Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009