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
Advanced Pancreatic Neuroendocrine Tumor, Locally Advanced Pancreatic Neuroendocrine Tumor, Pancreatic Gastrinoma
About this trial
This is an interventional treatment trial for Advanced Pancreatic Neuroendocrine Tumor
Eligibility Criteria
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
Sites / Locations
- Providence Hospital
- Kaiser Permanente-Anaheim
- Kaiser Permanente-Deer Valley Medical Center
- Kaiser Permanente-Baldwin Park
- Kaiser Permanente-Bellflower
- Alta Bates Summit Medical Center-Herrick Campus
- Mills-Peninsula Medical Center
- Kaiser Permanente-Fontana
- Kaiser Permanente-Fremont
- Kaiser Permanente-Fresno
- Kaiser Permanente - Harbor City
- Kaiser Permanente-Irvine
- Kaiser Permanente Los Angeles Medical Center
- Kaiser Permanente West Los Angeles
- Cedars Sinai Medical Center
- Sutter Cancer Research Consortium
- Kaiser Permanente-Oakland
- Stanford Cancer Institute Palo Alto
- Kaiser Permanente - Panorama City
- Kaiser Permanente-Redwood City
- Kaiser Permanente-Richmond
- Kaiser Permanente-Riverside
- Kaiser Permanente-Roseville
- Kaiser Permanente-South Sacramento
- Kaiser Permanente - Sacramento
- Kaiser Permanente-San Diego Mission
- Kaiser Permanente-San Diego Zion
- California Pacific Medical Center-Pacific Campus
- Kaiser Permanente-San Francisco
- UCSF Medical Center-Mount Zion
- Kaiser Permanente-Santa Teresa-San Jose
- Kaiser Permanente San Leandro
- Kaiser Permanente-San Marcos
- Kaiser Permanente-San Rafael
- Kaiser Permanente Medical Center - Santa Clara
- Kaiser Permanente-Santa Rosa
- Sutter Pacific Medical Foundation
- Kaiser Permanente-South San Francisco
- Kaiser Permanente-Stockton
- Kaiser Permanente Medical Center-Vacaville
- Kaiser Permanente-Vallejo
- Sutter Solano Medical Center/Cancer Center
- Kaiser Permanente-Walnut Creek
- Kaiser Permanente-Woodland Hills
- The Medical Center of Aurora
- Boulder Community Hospital
- Penrose-Saint Francis Healthcare
- Porter Adventist Hospital
- Presbyterian - Saint Lukes Medical Center - Health One
- SCL Health Saint Joseph Hospital
- Rose Medical Center
- Western States Cancer Research NCORP
- Swedish Medical Center
- Saint Mary's Hospital and Regional Medical Center
- North Colorado Medical Center
- Saint Anthony Hospital
- Littleton Adventist Hospital
- Sky Ridge Medical Center
- Longmont United Hospital
- McKee Medical Center
- Parker Adventist Hospital
- Saint Mary Corwin Medical Center
- North Suburban Medical Center
- SCL Health Lutheran Medical Center
- Smilow Cancer Hospital Care Center at Saint Francis
- The Hospital of Central Connecticut
- Beebe Medical Center
- Christiana Care Health System-Christiana Hospital
- MedStar Georgetown University Hospital
- MedStar Washington Hospital Center
- Lakeland Regional Health Hollis Cancer Center
- AdventHealth Orlando
- Augusta University Medical Center
- Pali Momi Medical Center
- Hawaii Cancer Care Inc - Waterfront Plaza
- Queen's Medical Center
- Straub Clinic and Hospital
- University of Hawaii Cancer Center
- Hawaii Cancer Care Inc-Liliha
- Queen's Cancer Center - Kuakini
- The Cancer Center of Hawaii-Liliha
- Kaiser Permanente Moanalua Medical Center
- Kapiolani Medical Center for Women and Children
- Castle Medical Center
- Wilcox Memorial Hospital and Kauai Medical Clinic
- Maui Memorial Medical Center
- Pacific Cancer Institute of Maui
- Saint Alphonsus Cancer Care Center-Boise
- Hematology and Oncology Associates
- Northwestern University
- University of Chicago Comprehensive Cancer Center
- Advocate Sherman Hospital
- Hematology Oncology Associates of Illinois-Highland Park
- Presence Saint Mary's Hospital
- AMITA Health Adventist Medical Center
- AMG Libertyville - Oncology
- Loyola University Medical Center
- Garneau, Stewart C MD (UIA Investigator)
- Porubcin, Michael MD (UIA Investigator)
- Spector, David MD (UIA Investigator)
- Trinity Medical Center
- Illinois Cancer Specialists-Niles
- Swedish American Hospital
- Hematology Oncology Associates of Illinois - Skokie
- Franciscan Saint Francis Health-Beech Grove
- Indiana University/Melvin and Bren Simon Cancer Center
- Sidney and Lois Eskenazi Hospital
- Reid Health
- McFarland Clinic PC - Ames
- Constantinou, Costas L MD (UIA Investigator)
- Medical Oncology and Hematology Associates-West Des Moines
- Mercy Cancer Center-West Lakes
- Iowa Methodist Medical Center
- Iowa-Wide Oncology Research Coalition NCORP
- Medical Oncology and Hematology Associates-Des Moines
- Medical Oncology and Hematology Associates-Laurel
- Mercy Medical Center - Des Moines
- Iowa Lutheran Hospital
- University of Iowa/Holden Comprehensive Cancer Center
- Ottumwa Regional Health Center
- Siouxland Regional Cancer Center
- Mercy Medical Center-Sioux City
- Saint Luke's Regional Medical Center
- Methodist West Hospital
- Mercy Medical Center-West Lakes
- Cancer Center of Kansas - Chanute
- Cancer Center of Kansas - Dodge City
- Cancer Center of Kansas - El Dorado
- Cancer Center of Kansas - Fort Scott
- Cancer Center of Kansas-Independence
- Cancer Center of Kansas-Kingman
- Lawrence Memorial Hospital
- Cancer Center of Kansas-Liberal
- Cancer Center of Kansas - McPherson
- Cancer Center of Kansas - Newton
- Menorah Medical Center
- Saint Luke's South Hospital
- Cancer Center of Kansas - Parsons
- Kansas City NCI Community Oncology Research Program
- Cancer Center of Kansas - Pratt
- Cancer Center of Kansas - Salina
- Cotton O'Neil Cancer Center / Stormont Vail Health
- Cancer Center of Kansas - Wellington
- Associates In Womens Health
- Cancer Center of Kansas-Wichita Medical Arts Tower
- Ascension Via Christi Hospitals Wichita
- Cancer Center of Kansas - Wichita
- Wichita NCI Community Oncology Research Program
- Cancer Center of Kansas - Winfield
- Ochsner Health Center-Summa
- Ochsner Health Center-Covington
- Ochsner Baptist Medical Center
- Ochsner Medical Center Jefferson
- Mercy Medical Center
- Christiana Care - Union Hospital
- Massachusetts General Hospital Cancer Center
- Dana-Farber Cancer Institute
- Bixby Medical Center
- Hickman Cancer Center
- Michigan Cancer Research Consortium NCORP
- Saint Joseph Mercy Hospital
- Bronson Battle Creek
- Spectrum Health Big Rapids Hospital
- Beaumont Hospital - Dearborn
- Ascension Saint John Hospital
- Green Bay Oncology - Escanaba
- Hurley Medical Center
- Genesys Regional Medical Center-West Flint Campus
- Genesys Regional Medical Center
- Cancer Research Consortium of West Michigan NCORP
- Mercy Health Saint Mary's
- Spectrum Health at Butterworth Campus
- Green Bay Oncology - Iron Mountain
- Allegiance Health
- Bronson Methodist Hospital
- West Michigan Cancer Center
- Borgess Medical Center
- Sparrow Hospital
- Trinity Health Saint Mary Mercy Livonia Hospital
- Mercy Memorial Hospital
- Toledo Clinic Cancer Centers-Monroe
- Mercy Health Mercy Campus
- Saint Joseph Mercy Oakland
- Lake Huron Medical Center
- Spectrum Health Reed City Hospital
- William Beaumont Hospital-Royal Oak
- Ascension Saint Mary's Hospital
- Munson Medical Center
- Saint John Macomb-Oakland Hospital
- Sanford Joe Lueken Cancer Center
- Essentia Health Saint Joseph's Medical Center
- Fairview Ridges Hospital
- Mercy Hospital
- Essentia Health Cancer Center
- Essentia Health Saint Mary's Medical Center
- Miller-Dwan Hospital
- Fairview Southdale Hospital
- Lake Region Healthcare Corporation-Cancer Care
- Unity Hospital
- Hutchinson Area Health Care
- Minnesota Oncology Hematology PA-Maplewood
- Saint John's Hospital - Healtheast
- Abbott-Northwestern Hospital
- Hennepin County Medical Center
- New Ulm Medical Center
- North Memorial Medical Health Center
- Mayo Clinic in Rochester
- Metro Minnesota Community Oncology Research Consortium
- Park Nicollet Clinic - Saint Louis Park
- Regions Hospital
- United Hospital
- Saint Francis Regional Medical Center
- Lakeview Hospital
- Ridgeview Medical Center
- Rice Memorial Hospital
- Minnesota Oncology Hematology PA-Woodbury
- Southeast Cancer Center
- University of Missouri - Ellis Fischel
- Capital Region Southwest Campus
- Saint Luke's Hospital of Kansas City
- North Kansas City Hospital
- Heartland Hematology and Oncology Associates Incorporated
- Research Medical Center
- Saint Luke's East - Lee's Summit
- Liberty Radiation Oncology Center
- Heartland Regional Medical Center
- Saint Joseph Oncology Inc
- SSM Health Saint Louis University Hospital
- Washington University School of Medicine
- Missouri Baptist Medical Center
- Comprehensive Cancer Care PC
- Billings Clinic Cancer Center
- Saint Vincent Healthcare
- Montana Cancer Consortium NCORP
- Saint Vincent Frontier Cancer Center
- Bozeman Deaconess Hospital
- Saint James Community Hospital and Cancer Treatment Center
- Benefis Healthcare- Sletten Cancer Institute
- Great Falls Clinic
- Northern Montana Hospital
- Saint Peter's Community Hospital
- Glacier Oncology PLLC
- Kalispell Medical Oncology
- Kalispell Regional Medical Center
- Montana Cancer Specialists
- Saint Patrick Hospital - Community Hospital
- CHI Health Saint Francis
- Great Plains Health Callahan Cancer Center
- Nebraska Methodist Hospital
- University of Nebraska Medical Center
- Dartmouth Hitchcock Medical Center
- Norris Cotton Cancer Center-Manchester
- Cooper Hospital University Medical Center
- Rutgers New Jersey Medical School
- New York Oncology Hematology PC - Albany
- New York Oncology Hematology PC - Albany Medical Center
- New York Oncology Hematology PC - Amsterdam
- Roswell Park Cancer Institute
- New York Oncology Hematology PC - Clifton Park
- Hematology Oncology Associates of Central New York-East Syracuse
- Glens Falls Hospital
- New York Oncology Hematology PC-Hudson
- Garnet Health Medical Center
- New York Oncology Hematology PC - Troy
- Novant Health Presbyterian Medical Center
- Wayne Memorial Hospital
- Iredell Memorial Hospital
- Wake Forest University Health Sciences
- Mid Dakota Clinic
- Saint Alexius Medical Center
- Sanford Bismarck Medical Center
- Sanford Broadway Medical Center
- Mary Rutan Hospital
- Toledo Clinic Cancer Centers-Bowling Green
- Adena Regional Medical Center
- North Coast Cancer Care-Clyde
- Ohio State University Comprehensive Cancer Center
- Riverside Methodist Hospital
- Columbus NCI Community Oncology Research Program
- Grant Medical Center
- Mount Carmel Health Center West
- Doctors Hospital
- Grandview Hospital
- Good Samaritan Hospital - Dayton
- Miami Valley Hospital
- Miami Valley Hospital North
- Dayton NCI Community Oncology Research Program
- Grady Memorial Hospital
- Hematology Oncology Center Incorporated
- Mercy Cancer Center-Elyria
- Blanchard Valley Hospital
- Atrium Medical Center-Middletown Regional Hospital
- Wayne Hospital
- Kettering Medical Center
- Fairfield Medical Center
- Lima Memorial Hospital
- Marietta Memorial Hospital
- Saint Luke's Hospital
- Toledo Clinic Cancer Centers-Maumee
- Toledo Radiation Oncology at Northwest Ohio Onocolgy Center
- Knox Community Hospital
- Licking Memorial Hospital
- Fisher-Titus Medical Center
- Saint Charles Hospital
- Toledo Clinic Cancer Centers-Oregon
- Southern Ohio Medical Center
- North Coast Cancer Care
- Springfield Regional Medical Center
- ProMedica Flower Hospital
- Mercy Hospital of Tiffin
- ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
- Saint Vincent Mercy Medical Center
- University of Toledo
- Toledo Community Hospital Oncology Program CCOP
- Mercy Health - Saint Anne Hospital
- Toledo Clinic Cancer Centers-Toledo
- Upper Valley Medical Center
- Fulton County Health Center
- Saint Ann's Hospital
- Clinton Memorial Hospital
- Greene Memorial Hospital
- Genesis Healthcare System Cancer Care Center
- University of Oklahoma Health Sciences Center
- Clackamas Radiation Oncology Center
- Providence Milwaukie Hospital
- Providence Newberg Medical Center
- Providence Willamette Falls Medical Center
- Providence Portland Medical Center
- Adventist Medical Center
- Providence Saint Vincent Medical Center
- Butler Memorial Hospital
- Geisinger Medical Center
- Geisinger Medical Center-Cancer Center Hazleton
- Pottstown Hospital
- Geisinger Medical Group
- Reading Hospital
- Geisinger Wyoming Valley/Henry Cancer Center
- Prisma Health Cancer Institute - Spartanburg
- Roper Hospital
- Saint Francis Hospital
- Prisma Health Cancer Institute - Butternut
- Prisma Health Cancer Institute - Faris
- Prisma Health Greenville Memorial Hospital
- Prisma Health Cancer Institute - Eastside
- Self Regional Healthcare
- Prisma Health Cancer Institute - Greer
- Prisma Health Cancer Institute - Seneca
- Avera Cancer Institute
- Avera McKennan Hospital and University Health Center
- Thompson Cancer Survival Center
- University of Tennessee - Knoxville
- The Don and Sybil Harrington Cancer Center
- Parkland Memorial Hospital
- UT Southwestern/Simmons Cancer Center-Dallas
- Huntsman Cancer Institute/University of Utah
- Fredericksburg Oncology Inc
- Cancer Care Center at Island Hospital
- PeaceHealth Saint Joseph Medical Center
- Harrison HealthPartners Hematology and Oncology-Bremerton
- Highline Medical Center-Main Campus
- Swedish Cancer Institute-Issaquah
- Kadlec Clinic Hematology and Oncology
- Skagit Valley Hospital
- Harrison HealthPartners Hematology and Oncology-Poulsbo
- Harborview Medical Center
- Fred Hutchinson Cancer Research Center
- Kaiser Permanente Washington
- Swedish Medical Center-First Hill
- University of Washington Medical Center - Montlake
- PeaceHealth United General Medical Center
- Cancer Care Northwest - Spokane South
- Evergreen Hematology and Oncology PS
- PeaceHealth Southwest Medical Center
- Compass Oncology Vancouver
- Wenatchee Valley Hospital and Clinics
- Green Bay Oncology at Saint Vincent Hospital
- Saint Vincent Hospital Cancer Center Green Bay
- Green Bay Oncology Limited at Saint Mary's Hospital
- Saint Vincent Hospital Cancer Center at Saint Mary's
- Gundersen Lutheran Medical Center
- Mayo Clinic Health System-Franciscan Healthcare
- Holy Family Memorial Hospital
- Bay Area Medical Center
- Saint Vincent Hospital Cancer Center at Oconto Falls
- HSHS Saint Nicholas Hospital
- Green Bay Oncology - Sturgeon Bay
- Rocky Mountain Oncology
- Welch Cancer Center
- BCCA-Vancouver Cancer Centre
- The Vitalite Health Network - Dr Leon Richard Oncology Centre
- QEII Health Sciences Centre/Nova Scotia Health Authority
- Ottawa Hospital and Cancer Center-General Campus
- University Health Network-Princess Margaret Hospital
- Allan Blair Cancer Centre
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Arm I (octreotide acetate and everolimus)
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 and octreotide acetate 20 mg IM on day 1.
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.