AMG 706 And Octreotide In Treating Patients With Low-Grade Neuroendocrine Tumors

Study Overview

AMG 706 and Octreotide in Treating 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.

Gastrointestinal Carcinoid Tumor
Islet Cell Tumor
Neoplastic Syndrome

DRUG: AMG 706
DRUG: octreotide

CDR0000526256
ECOG-E4206 (OTHER Identifier) (OTHER: Eastern Cooperative Oncology Group (ECOG))
U10CA023318 (U.S. NIH Grant/Contract)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2007-01-25	Results First Submitted 2015-05-19	Last Update Submitted that met QC Criteria 2023-06-20
First Submitted that Met QC Criteria 2007-01-25	Results First Submitted that Met QC Criteria 2015-05-19	Last Update Posted (ACTUAL) 2023-07-05
First Posted (ACTUAL) 2007-01-29	Results First Posted 2015-06-04	Last Verified 2023-06

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
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	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 trea 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.

Participant Group/Arm

Intervention/Treatment

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

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 trea

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.

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

Secondary Outcome Measures	Measure Description	Time Frame
Overall Survival	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	assessed every 3 months if patient is < 2 years from study entry, then every 6 months up to 5 years
Objective Response Rate	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.	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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)

Investigators

STUDY_CHAIR: Mary Mulcahy, MD, Robert H. Lurie Cancer Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Lubner S, Feng Y, Mulcahy M, O'Dwyer P, Giang GY, Hinshaw JL, Deming D, Klein L, Teitelbaum U, Payne J, Engstrom P, Stella P, Meropol N, Benson A. E4206: AMG 706 and Octreotide in Patients with Low-Grade Neuroendocrine Tumors. Oncologist. 2018 Sep;23(9):1006-e104. doi: 10.1634/theoncologist.2018-0294. Epub 2018 May 31.

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