Clinical trial NCT00427349: AMG 706 and Octreotide in Treating Patients With Low-Grade Neuroendocrine Tumors
Official title: A Phase II Clinical and Biologic Study of AMG 706 and Octreotide in Patients With Low-Grade Neuroendocrine Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Eastern Cooperative Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-01-29
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Four-month Progression-free Survival Rate
timeFrame: assessed every 4 weeks while on treatment and at three months post-treatment for participants treated for one cycle, up to month four
Secondary outcomes:
measure: Overall Survival
timeFrame: assessed every 3 months if patient is < 2 years from study entry, then every 6 months up to 5 years
measure: Objective Response Rate
timeFrame: 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
Other outcomes:
Locations:
city: Berwyn
country: United States
facility: Hematology Oncology Associates of Illinois - Berwyn
state: Illinois
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Hematology and Oncology Associates
state: Illinois
city: Joliet
country: United States
facility: Midwest Center for Hematology/Oncology
state: Illinois
city: Libertyville
country: United States
facility: North Shore Oncology and Hematology Associates, Limited - Libertyville
state: Illinois
city: Moline
country: United States
facility: Trinity Cancer Center at Trinity Medical Center - 7th Street Campus
state: Illinois
city: Naperville
country: United States
facility: La Grange Oncology Associates - Geneva
state: Illinois
city: Niles
country: United States
facility: Cancer Care and Hematology Specialists of Chicagoland - Niles
state: Illinois
city: Skokie
country: United States
facility: Hematology Oncology Associates - Skokie
state: Illinois
city: Ames
country: United States
facility: McFarland Clinic, PC
state: Iowa
city: Bettendorf
country: United States
facility: Hematology & Oncology Care
state: Iowa
city: Cedar Rapids
country: United States
facility: Cedar Rapids Oncology Associates
state: Iowa
city: Cedar Rapids
country: United States
facility: Mercy Regional Cancer Center at Mercy Medical Center
state: Iowa
city: Clive
country: United States
facility: Medical Oncology and Hematology Associates - West Des Moines
state: Iowa
city: Des Moines
country: United States
facility: Mercy Capitol Hospital
state: Iowa
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Des Moines
country: United States
facility: John Stoddard Cancer Center at Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates at John Stoddard Cancer Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates at Mercy Cancer Center
state: Iowa
city: Des Moines
country: United States
facility: Mercy Cancer Center at Mercy Medical Center - Des Moines
state: Iowa
city: Des Moines
country: United States
facility: John Stoddard Cancer Center at Iowa Lutheran Hospital
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology Associates, LLP
state: Iowa
city: Sioux City
country: United States
facility: Mercy Medical Center - Sioux City
state: Iowa
city: Sioux City
country: United States
facility: St. Luke's Regional Medical Center
state: Iowa
city: Chanute
country: United States
facility: Cancer Center of Kansas, PA - Chanute
state: Kansas
city: Dodge City
country: United States
facility: Cancer Center of Kansas, PA - Dodge City
state: Kansas
city: El Dorado
country: United States
facility: Cancer Center of Kansas, PA - El Dorado
state: Kansas
city: Fort Scott
country: United States
facility: Cancer Center of Kansas - Fort Scott
state: Kansas
city: Independence
country: United States
facility: Cancer Center of Kansas-Independence
state: Kansas
city: Kingman
country: United States
facility: Cancer Center of Kansas, PA - Kingman
state: Kansas
city: Lawrence
country: United States
facility: Lawrence Memorial Hospital
state: Kansas
city: Liberal
country: United States
facility: Southwest Medical Center
state: Kansas
city: Newton
country: United States
facility: Cancer Center of Kansas, PA - Newton
state: Kansas
city: Parsons
country: United States
facility: Cancer Center of Kansas, PA - Parsons
state: Kansas
city: Pratt
country: United States
facility: Cancer Center of Kansas, PA - Pratt
state: Kansas
city: Salina
country: United States
facility: Cancer Center of Kansas, PA - Salina
state: Kansas
city: Wellington
country: United States
facility: Cancer Center of Kansas, PA - Wellington
state: Kansas
city: Wichita
country: United States
facility: Associates in Womens Health, PA - North Review
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Medical Arts Tower
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Wichita
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Via Christi Cancer Center at Via Christi Regional Medical Center
state: Kansas
city: Winfield
country: United States
facility: Cancer Center of Kansas, PA - Winfield
state: Kansas
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Cancer Center
state: Michigan
city: Ann Arbor
country: United States
facility: CCOP - Michigan Cancer Research Consortium
state: Michigan
city: Dearborn
country: United States
facility: Oakwood Cancer Center at Oakwood Hospital and Medical Center
state: Michigan
city: Escanaba
country: United States
facility: Green Bay Oncology, Limited - Escanaba
state: Michigan
city: Flint
country: United States
facility: Genesys Hurley Cancer Institute
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Grosse Pointe Woods
country: United States
facility: Van Elslander Cancer Center at St. John Hospital and Medical Center
state: Michigan
city: Iron Mountain
country: United States
facility: Dickinson County Healthcare System
state: Michigan
city: Jackson
country: United States
facility: Foote Memorial Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: Borgess Medical Center
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Lansing
country: United States
facility: Sparrow Regional Cancer Center
state: Michigan
city: Livonia
country: United States
facility: St. Mary Mercy Hospital
state: Michigan
city: Pontiac
country: United States
facility: St. Joseph Mercy Oakland
state: Michigan
city: Port Huron
country: United States
facility: Mercy Regional Cancer Center at Mercy Hospital
state: Michigan
city: Saginaw
country: United States
facility: Seton Cancer Institute at Saint Mary's - Saginaw
state: Michigan
city: Warren
country: United States
facility: St. John Macomb Hospital
state: Michigan
city: Burnsville
country: United States
facility: Fairview Ridges Hospital
state: Minnesota
city: Coon Rapids
country: United States
facility: Mercy and Unity Cancer Center at Mercy Hospital
state: Minnesota
city: Edina
country: United States
facility: Fairview Southdale Hospital
state: Minnesota
city: Fridley
country: United States
facility: Mercy and Unity Cancer Center at Unity Hospital
state: Minnesota
city: Hutchinson
country: United States
facility: Hutchinson Area Health Care
state: Minnesota
city: Maplewood
country: United States
facility: HealthEast Cancer Care at St. John's Hospital
state: Minnesota
city: Maplewood
country: United States
facility: Minnesota Oncology Hematology, PA - Maplewood
state: Minnesota
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Hennepin County Medical Center - Minneapolis
state: Minnesota
city: Robbinsdale
country: United States
facility: Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Saint Louis Park
country: United States
facility: Park Nicollet Cancer Center
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital Cancer Care Center
state: Minnesota
city: Saint Paul
country: United States
facility: United Hospital
state: Minnesota
city: Shakopee
country: United States
facility: St. Francis Cancer Center at St. Francis Medical Center
state: Minnesota
city: Waconia
country: United States
facility: Ridgeview Medical Center
state: Minnesota
city: Woodbury
country: United States
facility: Minnesota Oncology Hematology, PA - Woodbury
state: Minnesota
city: Lincoln
country: United States
facility: Cancer Resource Center - Lincoln
state: Nebraska
city: Omaha
country: United States
facility: CCOP - Missouri Valley Cancer Consortium
state: Nebraska
city: Omaha
country: United States
facility: Immanuel Medical Center
state: Nebraska
city: Omaha
country: United States
facility: Alegant Health Cancer Center at Bergan Mercy Medical Center
state: Nebraska
city: Omaha
country: United States
facility: Creighton University Medical Center
state: Nebraska
city: Marlton
country: United States
facility: Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
state: New Jersey
city: Voorhees
country: United States
facility: Fox Chase Virtua Health Cancer Program at Virtua West Jersey
state: New Jersey
city: Akron
country: United States
facility: Summa Center for Cancer Care at Akron City Hospital
state: Ohio
city: Barberton
country: United States
facility: Barberton Citizens Hospital
state: Ohio
city: Cleveland
country: United States
facility: Case Comprehensive Cancer Center
state: Ohio
city: Lima
country: United States
facility: St. Rita's Medical Center
state: Ohio
city: Tulsa
country: United States
facility: Natalie Warren Bryant Cancer Center at St. Francis Hospital
state: Oklahoma
city: Danville
country: United States
facility: Geisinger Cancer Institute at Geisinger Health
state: Pennsylvania
city: Hazleton
country: United States
facility: Geisinger Hazleton Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Joan Karnell Cancer Center at Pennsylvania Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center - Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Centers
state: Pennsylvania
city: Reading
country: United States
facility: McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
state: Pennsylvania
city: State College
country: United States
facility: Geisinger Medical Group - Scenery Park
state: Pennsylvania
city: Wilkes-Barre
country: United States
facility: Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Medical X-Ray Center, PC
state: South Dakota
city: Sioux Falls
country: United States
facility: Sanford Cancer Center at Sanford USD Medical Center
state: South Dakota
city: Green Bay
country: United States
facility: Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center
state: Wisconsin
city: Green Bay
country: United States
facility: Green Bay Oncology, Limited at St. Mary's Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: St. Mary's Hospital Medical Center - Green Bay
state: Wisconsin
city: Green Bay
country: United States
facility: St. Vincent Hospital Regional Cancer Center
state: Wisconsin
city: La Crosse
country: United States
facility: Gundersen Lutheran Center for Cancer and Blood
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
state: Wisconsin
city: Manitowoc
country: United States
facility: Holy Family Memorial Medical Center Cancer Care Center
state: Wisconsin
city: Marinette
country: United States
facility: Bay Area Cancer Care Center at Bay Area Medical Center
state: Wisconsin
city: Oconto Falls
country: United States
facility: Green Bay Oncology, Limited - Oconto Falls
state: Wisconsin
city: Sturgeon Bay
country: United States
facility: Green Bay Oncology, Limited - Sturgeon Bay
state: Wisconsin
city: Wausau
country: United States
facility: University of Wisconcin Cancer Center at Aspirus Wausau Hospital
state: Wisconsin
Study officials:
affiliation: Robert H. Lurie Cancer Center
name: Mary Mulcahy, MD
role: STUDY_CHAIR
References:
citation: 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.