Everolimus and Octreotide Acetate With or Without Bevacizumab in Treating Patients With Locally Advanced or Metastatic Pancreatic Neuroendocrine Tumors That Cannot Be Removed by Surgery

Randomized Phase II Study of Everolimus Alone Versus Everolimus Plus Bevacizumab in Patients With Locally Advanced or Metastatic Pancreatic Neuroendocrine Tumors

This randomized phase II trial studies how well everolimus and octreotide acetate with or without bevacizumab works in treating patients with pancreatic neuroendocrine tumors that cannot be removed by surgery and have spread nearby or to other places in the body. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Octreotide acetate may interfere with and slow the growth of tumor cells. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab and everolimus also may stop the growth of pancreatic neuroendocrine tumors by blocking blood flow to the tumor. It is not yet known whether giving everolimus and octreotide acetate together is more effective with or without bevacizumab in treating pancreatic neuroendocrine tumors.

Study Overview

• Status: Completed
• Conditions: Locally Advanced Pancreatic Neuroendocrine Tumor; Pancreatic Neuroendocrine Tumor G1; Pancreatic Neuroendocrine Tumor G2; Pancreatic Vipoma; Pancreatic Gastrinoma; Advanced Pancreatic Neuroendocrine Tumor
• Intervention / Treatment: Drug: Everolimus; Biological: Bevacizumab; Drug: Octreotide Acetate

Detailed Description

PRIMARY OBJECTIVES:

l. To assess the progression-free survival rate of patients with locally advanced or metastatic pancreatic neuroendocrine tumors treated with everolimus alone or everolimus plus bevacizumab.

SECONDARY OBJECTIVES:

I. To compare progression-free survival (PFS) among treatment arms shown to be efficacious.

II. To estimate the overall tumor response rate in patients with metastatic pancreatic neuroendocrine tumors treated with one of two novel regimens.

III. To estimate the overall biochemical response rate (as measured by plasma chromogranin A levels) in patients with metastatic pancreatic neuroendocrine tumors treated with these regimens.

IV. To assess the toxicity of each regimen in patients with metastatic pancreatic neuroendocrine tumors.

V. To assess the overall survival of patients with pancreatic neuroendocrine tumors treated with these regimens.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive everolimus orally (PO) once daily (QD) on days 1-28 and octreotide acetate intramuscularly (IM) on day 1.

ARM II: Patients receive everolimus and octreotide acetate as in Arm I. Patients also receive bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3-6 months for 3 years.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BCCA-Vancouver Cancer Centre
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 8X3
      • The Vitalite Health Network - Dr Leon Richard Oncology Centre
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • QEII Health Sciences Centre/Nova Scotia Health Authority
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital and Cancer Center-General Campus
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network-Princess Margaret Hospital
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre
• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Providence Hospital
  • California
    • Anaheim, California, United States, 92806
      • Kaiser Permanente-Anaheim
    • Antioch, California, United States, 94531
      • Kaiser Permanente-Deer Valley Medical Center
    • Baldwin Park, California, United States, 91706
      • Kaiser Permanente-Baldwin Park
    • Bellflower, California, United States, 90706
      • Kaiser Permanente-Bellflower
    • Berkeley, California, United States, 94704
      • Alta Bates Summit Medical Center-Herrick Campus
    • Burlingame, California, United States, 94010
      • Mills-Peninsula Medical Center
    • Fontana, California, United States, 92335
      • Kaiser Permanente-Fontana
    • Fremont, California, United States, 94538
      • Kaiser Permanente-Fremont
    • Fresno, California, United States, 93720
      • Kaiser Permanente-Fresno
    • Harbor City, California, United States, 90710
      • Kaiser Permanente - Harbor City
    • Irvine, California, United States, 92618
      • Kaiser Permanente-Irvine
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente Los Angeles Medical Center
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
    • Los Angeles, California, United States, 90034
      • Kaiser Permanente West Los Angeles
    • Novato, California, United States, 94945
      • Sutter Cancer Research Consortium
    • Oakland, California, United States, 94611
      • Kaiser Permanente-Oakland
    • Palo Alto, California, United States, 94304
      • Stanford Cancer Institute Palo Alto
    • Panorama City, California, United States, 91402
      • Kaiser Permanente - Panorama City
    • Redwood City, California, United States, 94063
      • Kaiser Permanente-Redwood City
    • Richmond, California, United States, 94801
      • Kaiser Permanente-Richmond
    • Riverside, California, United States, 92505
      • Kaiser Permanente-Riverside
    • Roseville, California, United States, 95661
      • Kaiser Permanente-Roseville
    • Sacramento, California, United States, 95823
      • Kaiser Permanente-South Sacramento
    • Sacramento, California, United States, 95825
      • Kaiser Permanente - Sacramento
    • San Diego, California, United States, 92120
      • Kaiser Permanente-San Diego Zion
    • San Diego, California, United States, 92108
      • Kaiser Permanente-San Diego Mission
    • San Francisco, California, United States, 94115
      • Kaiser Permanente-San Francisco
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center-Pacific Campus
    • San Francisco, California, United States, 94115
      • UCSF Medical Center-Mount Zion
    • San Jose, California, United States, 95119
      • Kaiser Permanente-Santa Teresa-San Jose
    • San Leandro, California, United States, 94577
      • Kaiser Permanente San Leandro
    • San Marcos, California, United States, 92078
      • Kaiser Permanente-San Marcos
    • San Rafael, California, United States, 94903
      • Kaiser Permanente-San Rafael
    • Santa Clara, California, United States, 95051
      • Kaiser Permanente Medical Center - Santa Clara
    • Santa Rosa, California, United States, 95403
      • Kaiser Permanente-Santa Rosa
    • Santa Rosa, California, United States, 95403
      • Sutter Pacific Medical Foundation
    • South San Francisco, California, United States, 94080
      • Kaiser Permanente-South San Francisco
    • Stockton, California, United States, 95210
      • Kaiser Permanente-Stockton
    • Vacaville, California, United States, 95688
      • Kaiser Permanente Medical Center-Vacaville
    • Vallejo, California, United States, 94589
      • Kaiser Permanente-Vallejo
    • Vallejo, California, United States, 94589
      • Sutter Solano Medical Center/Cancer Center
    • Walnut Creek, California, United States, 94596
      • Kaiser Permanente-Walnut Creek
    • Woodland Hills, California, United States, 91367
      • Kaiser Permanente-Woodland Hills
  • Colorado
    • Aurora, Colorado, United States, 80012
      • The Medical Center of Aurora
    • Boulder, Colorado, United States, 80301
      • Boulder Community Hospital
    • Colorado Springs, Colorado, United States, 80907
      • Penrose-Saint Francis Healthcare
    • Denver, Colorado, United States, 80210
      • Porter Adventist Hospital
    • Denver, Colorado, United States, 80218
      • Presbyterian - Saint Lukes Medical Center - Health One
    • Denver, Colorado, United States, 80218
      • SCL Health Saint Joseph Hospital
    • Denver, Colorado, United States, 80220
      • Rose Medical Center
    • Denver, Colorado, United States, 80222
      • Western States Cancer Research NCORP
    • Englewood, Colorado, United States, 80113
      • Swedish Medical Center
    • Grand Junction, Colorado, United States, 81501
      • Saint Mary's Hospital and Regional Medical Center
    • Greeley, Colorado, United States, 80631
      • North Colorado Medical Center
    • Lakewood, Colorado, United States, 80228
      • Saint Anthony Hospital
    • Littleton, Colorado, United States, 80122
      • Littleton Adventist Hospital
    • Lone Tree, Colorado, United States, 80124
      • Sky Ridge Medical Center
    • Longmont, Colorado, United States, 80501
      • Longmont United Hospital
    • Loveland, Colorado, United States, 80539
      • McKee Medical Center
    • Parker, Colorado, United States, 80138
      • Parker Adventist Hospital
    • Pueblo, Colorado, United States, 81004
      • Saint Mary Corwin Medical Center
    • Thornton, Colorado, United States, 80229
      • North Suburban Medical Center
    • Wheat Ridge, Colorado, United States, 80033
      • SCL Health Lutheran Medical Center
  • Connecticut
    • Hartford, Connecticut, United States, 06105
      • Smilow Cancer Hospital Care Center at Saint Francis
    • New Britain, Connecticut, United States, 06050
      • The Hospital of Central Connecticut
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Beebe Medical Center
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • MedStar Washington Hospital Center
    • Washington, District of Columbia, United States, 20007
      • MedStar Georgetown University Hospital
  • Florida
    • Lakeland, Florida, United States, 33805
      • Lakeland Regional Health Hollis Cancer Center
    • Orlando, Florida, United States, 32803
      • AdventHealth Orlando
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University Medical Center
  • Hawaii
    • 'Aiea, Hawaii, United States, 96701
      • Pali Momi Medical Center
    • Honolulu, Hawaii, United States, 96813
      • Queen's Medical Center
    • Honolulu, Hawaii, United States, 96817
      • The Cancer Center of Hawaii-Liliha
    • Honolulu, Hawaii, United States, 96813
      • Hawaii Cancer Care Inc - Waterfront Plaza
    • Honolulu, Hawaii, United States, 96813
      • Straub Clinic and Hospital
    • Honolulu, Hawaii, United States, 96813
      • University of Hawaii Cancer Center
    • Honolulu, Hawaii, United States, 96817
      • Hawaii Cancer Care Inc-Liliha
    • Honolulu, Hawaii, United States, 96817
      • Queen's Cancer Center - Kuakini
    • Honolulu, Hawaii, United States, 96826
      • Kapiolani Medical Center for Women and Children
    • Honolulu, Hawaii, United States, 96819
      • Kaiser Permanente Moanalua Medical Center
    • Kailua, Hawaii, United States, 96734
      • Castle Medical Center
    • Lihue, Hawaii, United States, 96766
      • Wilcox Memorial Hospital and Kauai Medical Clinic
    • Wailuku, Hawaii, United States, 96793
      • Maui Memorial Medical Center
    • Wailuku, Hawaii, United States, 96793
      • Pacific Cancer Institute of Maui
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Cancer Care Center-Boise
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • Chicago, Illinois, United States, 60611
      • Hematology and Oncology Associates
    • Elgin, Illinois, United States, 60123
      • Advocate Sherman Hospital
    • Highland Park, Illinois, United States, 60035
      • Hematology Oncology Associates of Illinois-Highland Park
    • Kankakee, Illinois, United States, 60901
      • Presence Saint Mary's Hospital
    • La Grange, Illinois, United States, 60525
      • AMITA Health Adventist Medical Center
    • Libertyville, Illinois, United States, 60048
      • AMG Libertyville - Oncology
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Moline, Illinois, United States, 61265
      • Garneau, Stewart C MD (UIA Investigator)
    • Moline, Illinois, United States, 61265
      • Porubcin, Michael MD (UIA Investigator)
    • Moline, Illinois, United States, 61265
      • Spector, David MD (UIA Investigator)
    • Moline, Illinois, United States, 61265
      • Trinity Medical Center
    • Niles, Illinois, United States, 60714
      • Illinois Cancer Specialists-Niles
    • Rockford, Illinois, United States, 61104
      • Swedish American Hospital
    • Skokie, Illinois, United States, 60076
      • Hematology Oncology Associates of Illinois - Skokie
  • Indiana
    • Beech Grove, Indiana, United States, 46107
      • Franciscan Saint Francis Health-Beech Grove
    • Indianapolis, Indiana, United States, 46202
      • Indiana University/Melvin and Bren Simon Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • Sidney and Lois Eskenazi Hospital
    • Richmond, Indiana, United States, 47374
      • Reid Health
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic PC - Ames
    • Bettendorf, Iowa, United States, 52722
      • Constantinou, Costas L MD (UIA Investigator)
    • Clive, Iowa, United States, 50325
      • Mercy Cancer Center-West Lakes
    • Clive, Iowa, United States, 50325
      • Medical Oncology and Hematology Associates-West Des Moines
    • Des Moines, Iowa, United States, 50309
      • Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50309
      • Medical Oncology and Hematology Associates-Des Moines
    • Des Moines, Iowa, United States, 50316
      • Iowa Lutheran Hospital
    • Des Moines, Iowa, United States, 50309
      • Iowa-Wide Oncology Research Coalition NCORP
    • Des Moines, Iowa, United States, 50314
      • Medical Oncology and Hematology Associates-Laurel
    • Iowa City, Iowa, United States, 52242
      • University of Iowa/Holden Comprehensive Cancer Center
    • Ottumwa, Iowa, United States, 52501
      • Ottumwa Regional Health Center
    • Sioux City, Iowa, United States, 51101
      • Siouxland Regional Cancer Center
    • Sioux City, Iowa, United States, 51102
      • Mercy Medical Center-Sioux City
    • Sioux City, Iowa, United States, 51104
      • Saint Luke's Regional Medical Center
    • West Des Moines, Iowa, United States, 50266-7700
      • Methodist West Hospital
    • West Des Moines, Iowa, United States, 50266
      • Mercy Medical Center-West Lakes
  • Kansas
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas - Chanute
    • Dodge City, Kansas, United States, 67801
      • Cancer Center of Kansas - Dodge City
    • El Dorado, Kansas, United States, 67042
      • Cancer Center of Kansas - El Dorado
    • Fort Scott, Kansas, United States, 66701
      • Cancer Center of Kansas - Fort Scott
    • Independence, Kansas, United States, 67301
      • Cancer Center of Kansas-Independence
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas-Kingman
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Liberal, Kansas, United States, 67905
      • Cancer Center of Kansas-Liberal
    • McPherson, Kansas, United States, 67460
      • Cancer Center of Kansas - McPherson
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas - Newton
    • Overland Park, Kansas, United States, 66209
      • Menorah Medical Center
    • Overland Park, Kansas, United States, 66213
      • Saint Luke's South Hospital
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas - Parsons
    • Prairie Village, Kansas, United States, 66208
      • Kansas City NCI Community Oncology Research Program
    • Pratt, Kansas, United States, 67124
      • Cancer Center of Kansas - Pratt
    • Salina, Kansas, United States, 67401
      • Cancer Center of Kansas - Salina
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Cancer Center / Stormont Vail Health
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas - Wellington
    • Wichita, Kansas, United States, 67214
      • Ascension Via Christi Hospitals Wichita
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas-Wichita Medical Arts Tower
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas - Wichita
    • Wichita, Kansas, United States, 67208
      • Associates In Womens Health
    • Wichita, Kansas, United States, 67214
      • Wichita NCI Community Oncology Research Program
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas - Winfield
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Ochsner Health Center-Summa
    • Covington, Louisiana, United States, 70433
      • Ochsner Health Center-Covington
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center Jefferson
    • New Orleans, Louisiana, United States, 70115
      • Ochsner Baptist Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Mercy Medical Center
    • Elkton, Maryland, United States, 21921
      • Christiana Care - Union Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
  • Michigan
    • Adrian, Michigan, United States, 49221
      • Bixby Medical Center
    • Adrian, Michigan, United States, 49221
      • Hickman Cancer Center
    • Ann Arbor, Michigan, United States, 48106
      • Saint Joseph Mercy Hospital
    • Ann Arbor, Michigan, United States, 48106
      • Michigan Cancer Research Consortium NCORP
    • Battle Creek, Michigan, United States, 49017
      • Bronson Battle Creek
    • Big Rapids, Michigan, United States, 49307
      • Spectrum Health Big Rapids Hospital
    • Dearborn, Michigan, United States, 48124
      • Beaumont Hospital - Dearborn
    • Detroit, Michigan, United States, 48236
      • Ascension Saint John Hospital
    • Escanaba, Michigan, United States, 49829
      • Green Bay Oncology - Escanaba
    • Flint, Michigan, United States, 48532
      • Genesys Regional Medical Center-West Flint Campus
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Grand Blanc, Michigan, United States, 48439
      • Genesys Regional Medical Center
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health at Butterworth Campus
    • Grand Rapids, Michigan, United States, 49503
      • Mercy Health Saint Mary's
    • Grand Rapids, Michigan, United States, 49503
      • Cancer Research Consortium of West Michigan NCORP
    • Iron Mountain, Michigan, United States, 49801
      • Green Bay Oncology - Iron Mountain
    • Jackson, Michigan, United States, 49201
      • Allegiance Health
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49048
      • Borgess Medical Center
    • Lansing, Michigan, United States, 48912
      • Sparrow Hospital
    • Livonia, Michigan, United States, 48154
      • Trinity Health Saint Mary Mercy Livonia Hospital
    • Monroe, Michigan, United States, 48162
      • Mercy Memorial Hospital
    • Monroe, Michigan, United States, 48162
      • Toledo Clinic Cancer Centers-Monroe
    • Muskegon, Michigan, United States, 49444
      • Mercy Health Mercy Campus
    • Pontiac, Michigan, United States, 48341
      • Saint Joseph Mercy Oakland
    • Port Huron, Michigan, United States, 48060
      • Lake Huron Medical Center
    • Reed City, Michigan, United States, 49677
      • Spectrum Health Reed City Hospital
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital-Royal Oak
    • Saginaw, Michigan, United States, 48601
      • Ascension Saint Mary's Hospital
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
    • Warren, Michigan, United States, 48093
      • Saint John Macomb-Oakland Hospital
  • Minnesota
    • Bemidji, Minnesota, United States, 56601
      • Sanford Joe Lueken Cancer Center
    • Brainerd, Minnesota, United States, 56401
      • Essentia Health Saint Joseph's Medical Center
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Duluth, Minnesota, United States, 55805
      • Essentia Health Cancer Center
    • Duluth, Minnesota, United States, 55805
      • Essentia Health Saint Mary's Medical Center
    • Duluth, Minnesota, United States, 55805
      • Miller-Dwan Hospital
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Fergus Falls, Minnesota, United States, 56537
      • Lake Region Healthcare Corporation-Cancer Care
    • Fridley, Minnesota, United States, 55432
      • Unity Hospital
    • Hutchinson, Minnesota, United States, 55350
      • Hutchinson Area Health Care
    • Maplewood, Minnesota, United States, 55109
      • Saint John's Hospital - Healtheast
    • Maplewood, Minnesota, United States, 55109
      • Minnesota Oncology Hematology PA-Maplewood
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
    • Minneapolis, Minnesota, United States, 55407
      • Abbott-Northwestern Hospital
    • New Ulm, Minnesota, United States, 56073
      • New Ulm Medical Center
    • Robbinsdale, Minnesota, United States, 55422
      • North Memorial Medical Health Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Clinic - Saint Louis Park
    • Saint Louis Park, Minnesota, United States, 55416
      • Metro Minnesota Community Oncology Research Consortium
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Shakopee, Minnesota, United States, 55379
      • Saint Francis Regional Medical Center
    • Stillwater, Minnesota, United States, 55082
      • Lakeview Hospital
    • Waconia, Minnesota, United States, 55387
      • Ridgeview Medical Center
    • Willmar, Minnesota, United States, 56201
      • Rice Memorial Hospital
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology Hematology PA-Woodbury
  • Missouri
    • Cape Girardeau, Missouri, United States, 63703
      • Southeast Cancer Center
    • Columbia, Missouri, United States, 65212
      • University of Missouri - Ellis Fischel
    • Jefferson City, Missouri, United States, 65109
      • Capital Region Southwest Campus
    • Kansas City, Missouri, United States, 64116
      • North Kansas City Hospital
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital of Kansas City
    • Kansas City, Missouri, United States, 64132
      • Research Medical Center
    • Kansas City, Missouri, United States, 64118
      • Heartland Hematology and Oncology Associates Incorporated
    • Lee's Summit, Missouri, United States, 64086
      • Saint Luke's East - Lee's Summit
    • Liberty, Missouri, United States, 64068
      • Liberty Radiation Oncology Center
    • Saint Joseph, Missouri, United States, 64506
      • Heartland Regional Medical Center
    • Saint Joseph, Missouri, United States, 64507
      • Saint Joseph Oncology Inc
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63131
      • Missouri Baptist Medical Center
    • Saint Louis, Missouri, United States, 63104
      • SSM Health Saint Louis University Hospital
    • Saint Louis, Missouri, United States, 63141
      • Comprehensive Cancer Care PC
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic Cancer Center
    • Billings, Montana, United States, 59101
      • Saint Vincent Healthcare
    • Billings, Montana, United States, 59102
      • Montana Cancer Consortium NCORP
    • Billings, Montana, United States, 59102
      • Saint Vincent Frontier Cancer Center
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Hospital
    • Butte, Montana, United States, 59701
      • Saint James Community Hospital and Cancer Treatment Center
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic
    • Great Falls, Montana, United States, 59405
      • Benefis Healthcare- Sletten Cancer Institute
    • Havre, Montana, United States, 59501
      • Northern Montana Hospital
    • Helena, Montana, United States, 59601
      • Saint Peter's Community Hospital
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Kalispell, Montana, United States, 59901
      • Glacier Oncology PLLC
    • Kalispell, Montana, United States, 59901
      • Kalispell Medical Oncology
    • Missoula, Montana, United States, 59802
      • Saint Patrick Hospital - Community Hospital
    • Missoula, Montana, United States, 59802
      • Montana Cancer Specialists
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • CHI Health Saint Francis
    • North Platte, Nebraska, United States, 69101
      • Great Plains Health Callahan Cancer Center
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
    • Manchester, New Hampshire, United States, 03102
      • Norris Cotton Cancer Center-Manchester
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital University Medical Center
    • Newark, New Jersey, United States, 07101
      • Rutgers New Jersey Medical School
  • New York
    • Albany, New York, United States, 12206
      • New York Oncology Hematology PC - Albany
    • Albany, New York, United States, 12208
      • New York Oncology Hematology PC - Albany Medical Center
    • Amsterdam, New York, United States, 12010
      • New York Oncology Hematology PC - Amsterdam
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • Clifton Park, New York, United States, 12065
      • New York Oncology Hematology PC - Clifton Park
    • East Syracuse, New York, United States, 13057
      • Hematology Oncology Associates of Central New York-East Syracuse
    • Glens Falls, New York, United States, 12801
      • Glens Falls Hospital
    • Hudson, New York, United States, 12534
      • New York Oncology Hematology PC-Hudson
    • Middletown, New York, United States, 10940
      • Garnet Health Medical Center
    • Troy, New York, United States, 12180
      • New York Oncology Hematology PC - Troy
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Novant Health Presbyterian Medical Center
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital
    • Statesville, North Carolina, United States, 28677
      • Iredell Memorial Hospital
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Sanford Bismarck Medical Center
    • Bismarck, North Dakota, United States, 58501
      • Mid Dakota Clinic
    • Bismarck, North Dakota, United States, 58501
      • Saint Alexius Medical Center
    • Fargo, North Dakota, United States, 58122
      • Sanford Broadway Medical Center
  • Ohio
    • Bellefontaine, Ohio, United States, 43311
      • Mary Rutan Hospital
    • Bowling Green, Ohio, United States, 43402
      • Toledo Clinic Cancer Centers-Bowling Green
    • Chillicothe, Ohio, United States, 45601
      • Adena Regional Medical Center
    • Clyde, Ohio, United States, 43410
      • North Coast Cancer Care-Clyde
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
    • Columbus, Ohio, United States, 43228
      • Doctors Hospital
    • Columbus, Ohio, United States, 43215
      • Grant Medical Center
    • Columbus, Ohio, United States, 43222
      • Mount Carmel Health Center West
    • Columbus, Ohio, United States, 43215
      • Columbus NCI Community Oncology Research Program
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital - Dayton
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Miami Valley Hospital North
    • Dayton, Ohio, United States, 45405
      • Grandview Hospital
    • Dayton, Ohio, United States, 45459
      • Dayton NCI Community Oncology Research Program
    • Delaware, Ohio, United States, 43015
      • Grady Memorial Hospital
    • Elyria, Ohio, United States, 44035
      • Mercy Cancer Center-Elyria
    • Elyria, Ohio, United States, 44035
      • Hematology Oncology Center Incorporated
    • Findlay, Ohio, United States, 45840
      • Blanchard Valley Hospital
    • Franklin, Ohio, United States, 45005-1066
      • Atrium Medical Center-Middletown Regional Hospital
    • Greenville, Ohio, United States, 45331
      • Wayne Hospital
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Lancaster, Ohio, United States, 43130
      • Fairfield Medical Center
    • Lima, Ohio, United States, 45804
      • Lima Memorial Hospital
    • Marietta, Ohio, United States, 45750
      • Marietta Memorial Hospital
    • Maumee, Ohio, United States, 43537
      • Toledo Clinic Cancer Centers-Maumee
    • Maumee, Ohio, United States, 43537
      • Toledo Radiation Oncology at Northwest Ohio Onocolgy Center
    • Maumee, Ohio, United States, 43537
      • Saint Luke's Hospital
    • Mount Vernon, Ohio, United States, 43050
      • Knox Community Hospital
    • Newark, Ohio, United States, 43055
      • Licking Memorial Hospital
    • Norwalk, Ohio, United States, 44857
      • Fisher-Titus Medical Center
    • Oregon, Ohio, United States, 43616
      • Saint Charles Hospital
    • Oregon, Ohio, United States, 43616
      • Toledo Clinic Cancer Centers-Oregon
    • Portsmouth, Ohio, United States, 45662
      • Southern Ohio Medical Center
    • Sandusky, Ohio, United States, 44870
      • North Coast Cancer Care
    • Springfield, Ohio, United States, 45505
      • Springfield Regional Medical Center
    • Sylvania, Ohio, United States, 43560
      • ProMedica Flower Hospital
    • Tiffin, Ohio, United States, 44883
      • Mercy Hospital of Tiffin
    • Toledo, Ohio, United States, 43606
      • ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
    • Toledo, Ohio, United States, 43608
      • Saint Vincent Mercy Medical Center
    • Toledo, Ohio, United States, 43623
      • Mercy Health - Saint Anne Hospital
    • Toledo, Ohio, United States, 43623
      • Toledo Clinic Cancer Centers-Toledo
    • Toledo, Ohio, United States, 43614
      • University of Toledo
    • Toledo, Ohio, United States, 43617
      • Toledo Community Hospital Oncology Program CCOP
    • Troy, Ohio, United States, 45373
      • Upper Valley Medical Center
    • Wauseon, Ohio, United States, 43567
      • Fulton County Health Center
    • Westerville, Ohio, United States, 43081
      • Saint Ann's Hospital
    • Wilmington, Ohio, United States, 45177
      • Clinton Memorial Hospital
    • Xenia, Ohio, United States, 45385
      • Greene Memorial Hospital
    • Zanesville, Ohio, United States, 43701
      • Genesis Healthcare System Cancer Care Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Oregon
    • Clackamas, Oregon, United States, 97015
      • Clackamas Radiation Oncology Center
    • Milwaukie, Oregon, United States, 97222
      • Providence Milwaukie Hospital
    • Newberg, Oregon, United States, 97132
      • Providence Newberg Medical Center
    • Oregon City, Oregon, United States, 97045
      • Providence Willamette Falls Medical Center
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97225
      • Providence Saint Vincent Medical Center
    • Portland, Oregon, United States, 97216
      • Adventist Medical Center
  • Pennsylvania
    • Butler, Pennsylvania, United States, 16001
      • Butler Memorial Hospital
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Hazleton, Pennsylvania, United States, 18201
      • Geisinger Medical Center-Cancer Center Hazleton
    • Pottstown, Pennsylvania, United States, 19464
      • Pottstown Hospital
    • State College, Pennsylvania, United States, 16801
      • Geisinger Medical Group
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hospital
    • Wilkes-Barre, Pennsylvania, United States, 18711
      • Geisinger Wyoming Valley/Henry Cancer Center
  • South Carolina
    • Boiling Springs, South Carolina, United States, 29316
      • Prisma Health Cancer Institute - Spartanburg
    • Charleston, South Carolina, United States, 29401
      • Roper Hospital
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Cancer Institute - Faris
    • Greenville, South Carolina, United States, 29615
      • Prisma Health Cancer Institute - Eastside
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Cancer Institute - Butternut
    • Greenville, South Carolina, United States, 29601
      • Saint Francis Hospital
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Greenville Memorial Hospital
    • Greenwood, South Carolina, United States, 29646
      • Self Regional Healthcare
    • Greer, South Carolina, United States, 29650
      • Prisma Health Cancer Institute - Greer
    • Seneca, South Carolina, United States, 29672
      • Prisma Health Cancer Institute - Seneca
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute
    • Sioux Falls, South Dakota, United States, 57117-5045
      • Avera McKennan Hospital and University Health Center
  • Tennessee
    • Knoxville, Tennessee, United States, 37916
      • Thompson Cancer Survival Center
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee - Knoxville
  • Texas
    • Amarillo, Texas, United States, 79106
      • The Don and Sybil Harrington Cancer Center
    • Dallas, Texas, United States, 75235
      • Parkland Memorial Hospital
    • Dallas, Texas, United States, 75390
      • UT Southwestern/Simmons Cancer Center-Dallas
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
  • Virginia
    • Fredericksburg, Virginia, United States, 22401
      • Fredericksburg Oncology Inc
  • Washington
    • Anacortes, Washington, United States, 98221
      • Cancer Care Center at Island Hospital
    • Bellingham, Washington, United States, 98225
      • PeaceHealth Saint Joseph Medical Center
    • Bremerton, Washington, United States, 98310
      • Harrison HealthPartners Hematology and Oncology-Bremerton
    • Burien, Washington, United States, 98166
      • Highline Medical Center-Main Campus
    • Issaquah, Washington, United States, 98029
      • Swedish Cancer Institute-Issaquah
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and Oncology
    • Mount Vernon, Washington, United States, 98274
      • Skagit Valley Hospital
    • Poulsbo, Washington, United States, 98370
      • Harrison HealthPartners Hematology and Oncology-Poulsbo
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center - Montlake
    • Seattle, Washington, United States, 98112
      • Kaiser Permanente Washington
    • Seattle, Washington, United States, 98122-4307
      • Swedish Medical Center-First Hill
    • Sedro-Woolley, Washington, United States, 98284
      • PeaceHealth United General Medical Center
    • Spokane, Washington, United States, 99218
      • Evergreen Hematology and Oncology PS
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Vancouver, Washington, United States, 98664
      • PeaceHealth Southwest Medical Center
    • Vancouver, Washington, United States, 98684
      • Compass Oncology Vancouver
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Hospital and Clinics
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54301
      • Saint Vincent Hospital Cancer Center Green Bay
    • Green Bay, Wisconsin, United States, 54303
      • Saint Vincent Hospital Cancer Center at Saint Mary's
    • Green Bay, Wisconsin, United States, 54303
      • Green Bay Oncology Limited at Saint Mary's Hospital
    • Green Bay, Wisconsin, United States, 54301-3526
      • Green Bay Oncology at Saint Vincent Hospital
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Medical Center
    • La Crosse, Wisconsin, United States, 54601
      • Mayo Clinic Health System-Franciscan Healthcare
    • Manitowoc, Wisconsin, United States, 54221
      • Holy Family Memorial Hospital
    • Marinette, Wisconsin, United States, 54143
      • Bay Area Medical Center
    • Oconto Falls, Wisconsin, United States, 54154
      • Saint Vincent Hospital Cancer Center at Oconto Falls
    • Sheboygan, Wisconsin, United States, 53081
      • HSHS Saint Nicholas Hospital
    • Sturgeon Bay, Wisconsin, United States, 54235
      • Green Bay Oncology - Sturgeon Bay
  • Wyoming
    • Casper, Wyoming, United States, 82609
      • Rocky Mountain Oncology
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must have histologic documentation of well-differentiated or moderately differentiated neuroendocrine tumor from either a primary or metastatic site

  • If different histologic classification schemes are used, equivalent histologic classifications (for example "grade 1", "low-grade", or "intermediate-grade") are allowed
  • Patients with poorly differentiated neuroendocrine carcinoma or small cell carcinoma are excluded
  • Documentation from a metastatic disease site is sufficient if there is clinical evidence of a pancreatic primary site
• Locally unresectable or metastatic disease

• Patients must have either histologic documentation of a pancreatic primary site, or clinical evidence of a pancreatic neuroendocrine primary tumor as determined by the treating physician

  • Patients with neuroendocrine tumors (e.g., gastrinoma, VIPoma) in whom a pancreatic or peripancreatic primary site is strongly suspected are also eligible
• Patients must have evidence of disease (measurable or non-measurable) with evidence of progression within the past 12 months
• Measurable disease:

Lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 2 cm with conventional techniques or as >= 1 cm with spiral computed tomography (CT) scan

• Non-measurable disease:

All other lesions, including small lesions (longest diameter < 20 mm with conventional techniques or < 10 mm with spiral CT scan) and truly non-measurable lesions; lesions that are considered non-measurable include the following:

• Bone lesions
• Leptomeningeal disease
• Ascites
• Pleural/pericardial effusion
• Inflammatory breast disease
• Lymphangitis cutis/pulmonis
• Abdominal masses that are not confirmed and followed by imaging techniques

• Cystic lesions

  • No prior treatment with bevacizumab, everolimus, or other mammalian target of rapamycin (mTOR) inhibitors
  • Other prior treatments, including but not limited to prior cytotoxic chemotherapy, alpha interferon, tyrosine kinase inhibitors, external beam radiation therapy, and radiopeptide therapy are allowed
• There is no limit on the number of prior treatment regimens

• Any prior treatment (with the exception of octreotide) must be completed at least 4 weeks prior to initiation of treatment

  • Prior treatment with embolization or ablative therapies is allowed if measurable disease remains outside of the treated area

• There is no limit on the prior number of procedures

  • Treatment with somatostatin analogs is a requirement of the study
• Patients receiving octreotide at the time of study entry may continue at the same dose level for the duration of the study
• Patients not receiving octreotide will initiate treatment according to study guidelines

• Prior progression on somatostatin analogs or a negative octreotide scan does not exclude patient participation in this study

  • Patients should have completed any major surgery >= 4 weeks from start of treatment
• Patients must have completed any minor surgery >= 2 weeks prior to start of treatment
• Patients must have fully recovered from the procedure

• Insertion of a vascular access device is not considered major or minor surgery

  • Patients should not receive immunization with attenuated live vaccines within one week prior to registration or during protocol therapy
  • No concurrent condition resulting in immune compromise, including chronic treatment with corticosteroids or other immuno suppressive agents
  • No active or severe liver disease (e.g., acute or chronic hepatitis, cirrhosis); no positive anti-hepatitis B virus (HBV); HBV seropositive patients (hepatitis B surface antigen [HBsAg] positive) are eligible if they are closely monitored for evidence of active HBV infection by HBV deoxyribonucleic acid (DNA) testing, and they agree to receive suppressive therapy with lamivudine or other HBV-suppressive therapy until at least 4 weeks after the last dose of everolimus; patients who are hepatitis C antibody positive are eligible provided that hepatitis C viral load (hepatitis C ribonucleic acid [RNA]) is undetectable
  • No clinical evidence of brain metastases or carcinomatous meningitis
  • No history of gastrointestinal (GI) perforation within 12 months prior to registration
  • No history of clinically significant bleeding episodes
  • Patients on therapeutic anticoagulation are eligible for the study provided that they are on a stable dose of anticoagulants
  • No uncontrolled diabetes mellitus
  • Patients with a history of severely impaired lung function as defined as spirometry and diffusing capacity of the lung for carbon monoxide (DLCO) that is 50% of the normal predicted value and/or oxygen (O2) saturation that is 88% or less at rest on room air are excluded
  • Patients with fasting serum cholesterol >= 300 mg/dL OR >= 7.75 mmol/L AND fasting triglycerides >= 2.5 X upper limit of normal (ULN) should initiate lipid-lowering medications with the goal of achieving levels below these thresholds
  • No history of intolerance or allergies to octreotide
  • Patients with a history of hypertension must be adequately controlled (baseline blood pressure [BP] < 150/90 mm Hg) on antihypertensives
  • No current congestive heart failure (New York Heart Association class II, III, or IV)
  • No symptomatic arterial peripheral vascular disease
  • No history of aortic aneurysm, aortic dissection, angina, myocardial infarction, stroke, or other arterial thrombotic events within 6 months of registration
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Women must not be pregnant or lactating; both men and women of childbearing potential must be advised of the importance of using effective birth control measures during the course of the study
  • Granulocytes >= 1,500/uL
  • Platelets >= 100,000/uL
  • Creatinine =< 1.5 x upper limit of normal
  • Bilirubin =< 1.5 x upper limit of normal
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x upper limit of normal (=< 5 x upper limit of normal if liver metastases present)
  • Urine protein =< 1+ OR urine creatinine ratio =< 1 (by urinalysis)
• If urine protein creatinine (UPC) ratio is > 1 on urinalysis, then 24-hour urine collection for protein must be obtained and level must be < 1,000 mg for patient enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm I (octreotide acetate and everolimus); Patients receive 28-day cycles until progression or unacceptable toxicity consisting of: everolimus 10 mg PO QD on days 1-28 and octreotide acetate 20 mg IM on day 1.	Drug: Everolimus; Given PO; Other Names: 42-O-(2-Hydroxy)ethyl Rapamycin; Afinitor; Certican; RAD 001; RAD001; Votubia; Zortress; Drug: Octreotide Acetate; Given IM; Other Names: Sandostatin; D-Phenylalanyl-L-cysteinyl-L-phenylalanyl-D-tryptophyl-L-lysyl-L-threonyl-N-[(1R,2R)-2-hydroxy-1-(hyroxymethyl)propyl]-L-cysteinamide, Cyclic (2->7)-disulfide, Acetate (Salt); Longastatin; Longastatina; Samilstin; Sandostatin Lar Depot; Sandostatina; Sandostatine; SMS 201-995; SMS 201-995 AC
EXPERIMENTAL: Arm II (octreotide acetate, everolimus, and bevacizumab); Patients receive 28-day cycles until progression or unacceptable toxicity consisting of: everolimus 10 mg PO QD on days 1-28, octreotide acetate 20 mg IM on day 1 and bevacizumab 10 mg/kg IV on days 1 and 15.	Drug: Everolimus; Given PO; Other Names: 42-O-(2-Hydroxy)ethyl Rapamycin; Afinitor; Certican; RAD 001; RAD001; Votubia; Zortress; Biological: Bevacizumab; Given IV; Other Names: Avastin; ABP 215; Anti-VEGF; Anti-VEGF Humanized Monoclonal Antibody; Anti-VEGF Monoclonal Antibody SIBP04; Anti-VEGF rhuMAb; Bevacizumab awwb; Bevacizumab Biosimilar ABP 215; Bevacizumab Biosimilar BEVZ92; Bevacizumab Biosimilar BI 695502; Bevacizumab Biosimilar CBT 124; Bevacizumab Biosimilar CT-P16; Bevacizumab Biosimilar FKB238; Bevacizumab Biosimilar GB-222; Bevacizumab Biosimilar HD204; Bevacizumab Biosimilar HLX04; Bevacizumab Biosimilar IBI305; Bevacizumab Biosimilar LY01008; Bevacizumab Biosimilar MIL60; Bevacizumab Biosimilar Mvasi; Bevacizumab Biosimilar MYL-1402O; Bevacizumab Biosimilar QL 1101; Bevacizumab Biosimilar RPH-001; Bevacizumab Biosimilar SCT501; Bevacizumab Biosimilar Zirabev; Bevacizumab-awwb; Bevacizumab-bvzr; BP102; BP102 Biosimilar; HD204; Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer; Mvasi; MYL-1402O; Recombinant Humanized Anti-VEGF Monoclonal Antibody; rhuMab-VEGF; SCT501; SIBP 04; SIBP-04; SIBP04; Zirabev; Drug: Octreotide Acetate; Given IM; Other Names: Sandostatin; D-Phenylalanyl-L-cysteinyl-L-phenylalanyl-D-tryptophyl-L-lysyl-L-threonyl-N-[(1R,2R)-2-hydroxy-1-(hyroxymethyl)propyl]-L-cysteinamide, Cyclic (2->7)-disulfide, Acetate (Salt); Longastatin; Longastatina; Samilstin; Sandostatin Lar Depot; Sandostatina; Sandostatine; SMS 201-995; SMS 201-995 AC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Progression Free Survival (PFS) was defined as the time from study entry until disease progression or death, whichever occurs first. The median PFS was estimated using the Kaplan-Meier method. Progression was assessed per RECIST criteria, and defined as at least a 20% increase in the sum of the longest diameters of target lesions (and an absolute increase of at least 0.5 cm) or the appearance of new lesions.	From study entry to the date of documented progression or death from any cause, up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	The proportion of patients who respond (completely or partially) to each combination regimen will be estimated. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR): disappearance of all target lesions; Partial Response (PR) 30% decrease in sum of longest diameter of target lesions.	Up to 3 years
Overall Survival (OS)	Overall survival (OS) is defined as the time from study entry to death from any cause. The median OS was estimated using the Kaplan-Meier method.	From registration to time of death, assessed up to 3 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Matthew H Kulke, Alliance for Clinical Trials in Oncology

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 15, 2010
• Primary Completion (ACTUAL): September 1, 2014
• Study Completion (ACTUAL): January 3, 2018

Study Registration Dates

• First Submitted: October 27, 2010
• First Submitted That Met QC Criteria: October 27, 2010
• First Posted (ESTIMATE): October 28, 2010

Study Record Updates

• Last Update Posted (ACTUAL): August 4, 2022
• Last Update Submitted That Met QC Criteria: August 3, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Pancreatic Diseases; Adenoma; Carcinoma, Neuroendocrine; Pancreatic Neoplasms; Carcinoma, Islet Cell; Neoplasms; Neuroendocrine Tumors; Adenoma, Islet Cell; Gastrinoma; Vipoma; Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Antibodies; Immunoglobulins; Bevacizumab; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Octreotide; Everolimus; Immunoglobulin G; Endothelial Growth Factors
• Other Study ID Numbers: NCI-2011-02609 (REGISTRY: CTRP (Clinical Trial Reporting Program)); U10CA180821 (U.S. NIH Grant/Contract); U10CA031946 (U.S. NIH Grant/Contract); CDR0000687459; CALGB-80701 (OTHER: CTEP)