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

Pancreatic Neuroendocrine Tumor G2 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01229943
• Other study ID #: NCI-2011-02609
• Secondary ID: NCI-2011-02609CD
• Status: Completed
• Phase: Phase 2
• Start date: October 15, 2010
• Est. completion date: January 3, 2018

Study information

• Verified date: August 2022
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: January 3, 2018
• Est. primary completion date: September 1, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Pancreatic Neuroendocrine Tumor
• Gastrinoma
• Locally Advanced Pancreatic Neuroendocrine Tumor
• Neoplasms
• Neuroendocrine Tumors
• Pancreatic Gastrinoma
• Pancreatic Neuroendocrine Tumor G1
• Pancreatic Neuroendocrine Tumor G2
• Pancreatic Vipoma
• Vipoma

Intervention

Biological:
• Bevacizumab
Given IV

Drug:
• Everolimus
Given PO
• Octreotide Acetate
Given IM

Locations

Country	Name	City	State
Canada	QEII Health Sciences Centre/Nova Scotia Health Authority	Halifax	Nova Scotia
Canada	The Vitalite Health Network - Dr Leon Richard Oncology Centre	Moncton	New Brunswick
Canada	Ottawa Hospital and Cancer Center-General Campus	Ottawa	Ontario
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	University Health Network-Princess Margaret Hospital	Toronto	Ontario
Canada	BCCA-Vancouver Cancer Centre	Vancouver	British Columbia
United States	Pali Momi Medical Center	'Aiea	Hawaii
United States	Bixby Medical Center	Adrian	Michigan
United States	Hickman Cancer Center	Adrian	Michigan
United States	New York Oncology Hematology PC - Albany	Albany	New York
United States	New York Oncology Hematology PC - Albany Medical Center	Albany	New York
United States	The Don and Sybil Harrington Cancer Center	Amarillo	Texas
United States	McFarland Clinic PC - Ames	Ames	Iowa
United States	New York Oncology Hematology PC - Amsterdam	Amsterdam	New York
United States	Cancer Care Center at Island Hospital	Anacortes	Washington
United States	Kaiser Permanente-Anaheim	Anaheim	California
United States	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Kaiser Permanente-Deer Valley Medical Center	Antioch	California
United States	Augusta University Medical Center	Augusta	Georgia
United States	The Medical Center of Aurora	Aurora	Colorado
United States	Kaiser Permanente-Baldwin Park	Baldwin Park	California
United States	Mercy Medical Center	Baltimore	Maryland
United States	Ochsner Health Center-Summa	Baton Rouge	Louisiana
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	Franciscan Saint Francis Health-Beech Grove	Beech Grove	Indiana
United States	Mary Rutan Hospital	Bellefontaine	Ohio
United States	Kaiser Permanente-Bellflower	Bellflower	California
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
United States	Constantinou, Costas L MD (UIA Investigator)	Bettendorf	Iowa
United States	Spectrum Health Big Rapids Hospital	Big Rapids	Michigan
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Montana Cancer Consortium NCORP	Billings	Montana
United States	Saint Vincent Frontier Cancer Center	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	Mid Dakota Clinic	Bismarck	North Dakota
United States	Saint Alexius Medical Center	Bismarck	North Dakota
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Boulder Community Hospital	Boulder	Colorado
United States	Toledo Clinic Cancer Centers-Bowling Green	Bowling Green	Ohio
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Essentia Health Saint Joseph's Medical Center	Brainerd	Minnesota
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Mills-Peninsula Medical Center	Burlingame	California
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Butler Memorial Hospital	Butler	Pennsylvania
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Rocky Mountain Oncology	Casper	Wyoming
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	Roper Hospital	Charleston	South Carolina
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	Hematology and Oncology Associates	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	New York Oncology Hematology PC - Clifton Park	Clifton Park	New York
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	North Coast Cancer Care-Clyde	Clyde	Ohio
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	University of Missouri - Ellis Fischel	Columbia	Missouri
United States	Columbus NCI Community Oncology Research Program	Columbus	Ohio
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Ochsner Health Center-Covington	Covington	Louisiana
United States	Parkland Memorial Hospital	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Dayton NCI Community Oncology Research Program	Dayton	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Miami Valley Hospital North	Dayton	Ohio
United States	Beaumont Hospital - Dearborn	Dearborn	Michigan
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	SCL Health Saint Joseph Hospital	Denver	Colorado
United States	Western States Cancer Research NCORP	Denver	Colorado
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota
United States	Miller-Dwan Hospital	Duluth	Minnesota
United States	Hematology Oncology Associates of Central New York-East Syracuse	East Syracuse	New York
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Advocate Sherman Hospital	Elgin	Illinois
United States	Christiana Care - Union Hospital	Elkton	Maryland
United States	Hematology Oncology Center Incorporated	Elyria	Ohio
United States	Mercy Cancer Center-Elyria	Elyria	Ohio
United States	Swedish Medical Center	Englewood	Colorado
United States	Green Bay Oncology - Escanaba	Escanaba	Michigan
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Lake Region Healthcare Corporation-Cancer Care	Fergus Falls	Minnesota
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Kaiser Permanente-Fontana	Fontana	California
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Fredericksburg Oncology Inc	Fredericksburg	Virginia
United States	Kaiser Permanente-Fremont	Fremont	California
United States	Kaiser Permanente-Fresno	Fresno	California
United States	Unity Hospital	Fridley	Minnesota
United States	Glens Falls Hospital	Glens Falls	New York
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Genesys Regional Medical Center	Grand Blanc	Michigan
United States	CHI Health Saint Francis	Grand Island	Nebraska
United States	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado
United States	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan
United States	Mercy Health Saint Mary's	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	North Colorado Medical Center	Greeley	Colorado
United States	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Self Regional Healthcare	Greenwood	South Carolina
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	Kaiser Permanente - Harbor City	Harbor City	California
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Northern Montana Hospital	Havre	Montana
United States	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania
United States	Saint Peter's Community Hospital	Helena	Montana
United States	Hematology Oncology Associates of Illinois-Highland Park	Highland Park	Illinois
United States	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii
United States	Hawaii Cancer Care Inc-Liliha	Honolulu	Hawaii
United States	Kaiser Permanente Moanalua Medical Center	Honolulu	Hawaii
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Queen's Cancer Center - Kuakini	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	New York Oncology Hematology PC-Hudson	Hudson	New York
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Sidney and Lois Eskenazi Hospital	Indianapolis	Indiana
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan
United States	Kaiser Permanente-Irvine	Irvine	California
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	Allegiance Health	Jackson	Michigan
United States	Capital Region Southwest Campus	Jefferson City	Missouri
United States	Castle Medical Center	Kailua	Hawaii
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Glacier Oncology PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Presence Saint Mary's Hospital	Kankakee	Illinois
United States	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri
United States	North Kansas City Hospital	Kansas City	Missouri
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	Kettering Medical Center	Kettering	Ohio
United States	Cancer Center of Kansas-Kingman	Kingman	Kansas
United States	Thompson Cancer Survival Center	Knoxville	Tennessee
United States	University of Tennessee - Knoxville	Knoxville	Tennessee
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	Mayo Clinic Health System-Franciscan Healthcare	La Crosse	Wisconsin
United States	AMITA Health Adventist Medical Center	La Grange	Illinois
United States	Lakeland Regional Health Hollis Cancer Center	Lakeland	Florida
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Sparrow Hospital	Lansing	Michigan
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	Beebe Medical Center	Lewes	Delaware
United States	Cancer Center of Kansas-Liberal	Liberal	Kansas
United States	Liberty Radiation Oncology Center	Liberty	Missouri
United States	AMG Libertyville - Oncology	Libertyville	Illinois
United States	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii
United States	Lima Memorial Hospital	Lima	Ohio
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Longmont United Hospital	Longmont	Colorado
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Kaiser Permanente West Los Angeles	Los Angeles	California
United States	McKee Medical Center	Loveland	Colorado
United States	Norris Cotton Cancer Center-Manchester	Manchester	New Hampshire
United States	Holy Family Memorial Hospital	Manitowoc	Wisconsin
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	Bay Area Medical Center	Marinette	Wisconsin
United States	Saint Luke's Hospital	Maumee	Ohio
United States	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio
United States	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	Cancer Center of Kansas - McPherson	McPherson	Kansas
United States	Garnet Health Medical Center	Middletown	New York
United States	Providence Milwaukie Hospital	Milwaukie	Oregon
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Montana Cancer Specialists	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Providence Hospital	Mobile	Alabama
United States	Garneau, Stewart C MD (UIA Investigator)	Moline	Illinois
United States	Porubcin, Michael MD (UIA Investigator)	Moline	Illinois
United States	Spector, David MD (UIA Investigator)	Moline	Illinois
United States	Trinity Medical Center	Moline	Illinois
United States	Mercy Memorial Hospital	Monroe	Michigan
United States	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	Skagit Valley Hospital	Mount Vernon	Washington
United States	Mercy Health Mercy Campus	Muskegon	Michigan
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	Ochsner Baptist Medical Center	New Orleans	Louisiana
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	New Ulm Medical Center	New Ulm	Minnesota
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Licking Memorial Hospital	Newark	Ohio
United States	Rutgers New Jersey Medical School	Newark	New Jersey
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	Illinois Cancer Specialists-Niles	Niles	Illinois
United States	Great Plains Health Callahan Cancer Center	North Platte	Nebraska
United States	Fisher-Titus Medical Center	Norwalk	Ohio
United States	Sutter Cancer Research Consortium	Novato	California
United States	Kaiser Permanente-Oakland	Oakland	California
United States	Saint Vincent Hospital Cancer Center at Oconto Falls	Oconto Falls	Wisconsin
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Saint Charles Hospital	Oregon	Ohio
United States	Toledo Clinic Cancer Centers-Oregon	Oregon	Ohio
United States	Providence Willamette Falls Medical Center	Oregon City	Oregon
United States	AdventHealth Orlando	Orlando	Florida
United States	Ottumwa Regional Health Center	Ottumwa	Iowa
United States	Menorah Medical Center	Overland Park	Kansas
United States	Saint Luke's South Hospital	Overland Park	Kansas
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	Kaiser Permanente - Panorama City	Panorama City	California
United States	Parker Adventist Hospital	Parker	Colorado
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Lake Huron Medical Center	Port Huron	Michigan
United States	Adventist Medical Center	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Pottstown Hospital	Pottstown	Pennsylvania
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington
United States	Kansas City NCI Community Oncology Research Program	Prairie Village	Kansas
United States	Cancer Center of Kansas - Pratt	Pratt	Kansas
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Kaiser Permanente-Redwood City	Redwood City	California
United States	Spectrum Health Reed City Hospital	Reed City	Michigan
United States	Kaiser Permanente-Richmond	Richmond	California
United States	Reid Health	Richmond	Indiana
United States	Kaiser Permanente-Riverside	Riverside	California
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	Swedish American Hospital	Rockford	Illinois
United States	Kaiser Permanente-Roseville	Roseville	California
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	Kaiser Permanente - Sacramento	Sacramento	California
United States	Kaiser Permanente-South Sacramento	Sacramento	California
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Saint Joseph Oncology Inc	Saint Joseph	Missouri
United States	Comprehensive Cancer Care PC	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	SSM Health Saint Louis University Hospital	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Kaiser Permanente-San Diego Mission	San Diego	California
United States	Kaiser Permanente-San Diego Zion	San Diego	California
United States	California Pacific Medical Center-Pacific Campus	San Francisco	California
United States	Kaiser Permanente-San Francisco	San Francisco	California
United States	UCSF Medical Center-Mount Zion	San Francisco	California
United States	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California
United States	Kaiser Permanente San Leandro	San Leandro	California
United States	Kaiser Permanente-San Marcos	San Marcos	California
United States	Kaiser Permanente-San Rafael	San Rafael	California
United States	North Coast Cancer Care	Sandusky	Ohio
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Kaiser Permanente-Santa Rosa	Santa Rosa	California
United States	Sutter Pacific Medical Foundation	Santa Rosa	California
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Harborview Medical Center	Seattle	Washington
United States	Kaiser Permanente Washington	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	University of Washington Medical Center - Montlake	Seattle	Washington
United States	PeaceHealth United General Medical Center	Sedro-Woolley	Washington
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	HSHS Saint Nicholas Hospital	Sheboygan	Wisconsin
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Mercy Medical Center-Sioux City	Sioux City	Iowa
United States	Saint Luke's Regional Medical Center	Sioux City	Iowa
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Avera McKennan Hospital and University Health Center	Sioux Falls	South Dakota
United States	Hematology Oncology Associates of Illinois - Skokie	Skokie	Illinois
United States	Kaiser Permanente-South San Francisco	South San Francisco	California
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Evergreen Hematology and Oncology PS	Spokane	Washington
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Geisinger Medical Group	State College	Pennsylvania
United States	Iredell Memorial Hospital	Statesville	North Carolina
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Kaiser Permanente-Stockton	Stockton	California
United States	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	North Suburban Medical Center	Thornton	Colorado
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	Mercy Health - Saint Anne Hospital	Toledo	Ohio
United States	ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital	Toledo	Ohio
United States	Saint Vincent Mercy Medical Center	Toledo	Ohio
United States	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio
United States	Toledo Community Hospital Oncology Program CCOP	Toledo	Ohio
United States	University of Toledo	Toledo	Ohio
United States	Cotton O'Neil Cancer Center / Stormont Vail Health	Topeka	Kansas
United States	Munson Medical Center	Traverse City	Michigan
United States	New York Oncology Hematology PC - Troy	Troy	New York
United States	Upper Valley Medical Center	Troy	Ohio
United States	Kaiser Permanente Medical Center-Vacaville	Vacaville	California
United States	Kaiser Permanente-Vallejo	Vallejo	California
United States	Sutter Solano Medical Center/Cancer Center	Vallejo	California
United States	Compass Oncology Vancouver	Vancouver	Washington
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Maui Memorial Medical Center	Wailuku	Hawaii
United States	Pacific Cancer Institute of Maui	Wailuku	Hawaii
United States	Kaiser Permanente-Walnut Creek	Walnut Creek	California
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	MedStar Washington Hospital Center	Washington	District of Columbia
United States	Fulton County Health Center	Wauseon	Ohio
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Methodist West Hospital	West Des Moines	Iowa
United States	Reading Hospital	West Reading	Pennsylvania
United States	Saint Ann's Hospital	Westerville	Ohio
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	Ascension Via Christi Hospitals Wichita	Wichita	Kansas
United States	Associates In Womens Health	Wichita	Kansas
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Wichita NCI Community Oncology Research Program	Wichita	Kansas
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Clinton Memorial Hospital	Wilmington	Ohio
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Kaiser Permanente-Woodland Hills	Woodland Hills	California
United States	Greene Memorial Hospital	Xenia	Ohio
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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