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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT00427349
First received: January 25, 2007
Last updated: May 19, 2015
Last verified: May 2015

January 25, 2007
May 19, 2015
September 2008
October 2014   (final data collection date for primary outcome measure)
Four-month Progression-free Survival Rate [ Time Frame: assessed every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry ] [ Designated as safety issue: No ]
Four-month progression-free survival (PFS) rate is defined as number of patients who are still progression free at 4 months after study entry divided by number of eligible and treated patients enrolled to the study. Progression is evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, and defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s), or unequivocal progression of existing non-target lesions.
  • Time to progression
  • Progression-free survival at 4 months
Complete list of historical versions of study NCT00427349 on ClinicalTrials.gov Archive Site
  • Overall Survival [ Time Frame: assessed every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Objective response rate is defined as complete
  • 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
Not Provided
Not Provided
 
AMG 706 and Octreotide in Treating Patients With Low-Grade Neuroendocrine Tumors
A Phase II Clinical and Biologic Study of AMG 706 and Octreotide in Patients With Low-Grade Neuroendocrine Tumors

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.

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.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Gastrointestinal Carcinoid Tumor
  • Islet Cell Tumor
  • Neoplastic Syndrome
  • Drug: AMG 706
    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
    Other Name: motesanib diphosphate
  • Drug: octreotide
    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.
    Other Names:
    • L-cysteinamide
    • Sandostatin
    • SMS 201-995
Experimental: AMG 706+Octreotide

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:
  • Drug: AMG 706
  • Drug: octreotide
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
46
April 2015
October 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Must be able to receive a contrast-enhanced CT scan
  • 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)
  • Aspartate aminotransferase (AST) ≤ 3 times ULN (5 times ULN if liver metastases are present)
  • Left Ventricular Ejection Fraction (LVEF) ≥ institutional lower limit of normal as evaluated by echocardiography or multigated acquisition (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
  • 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

Exclusion criteria:

  • Prior procedures that would adversely affect intestinal absorption
  • Prior anti-vascular endothelial growth factors
  • Concurrent chemotherapy or radiation therapy
  • 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
    • Arterial or venous thrombosis
  • Known history of allergic reactions to AMG 706 or derivatives or to octreotide acetate injections
  • 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)
  • Pregnant or nursing
  • Small cell lung cancer, medullary thyroid cancer, paraganglioma, or pheochromocytoma
  • Requirement for intravenous alimentation
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00427349
CDR0000526256, ECOG-E4206, U10CA023318
Yes
Eastern Cooperative Oncology Group
Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
Study Chair: Mary Mulcahy, MD Robert H. Lurie Cancer Center
Eastern Cooperative Oncology Group
May 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP