Cisplatin, Carboplatin and Etoposide or Temozolomide and Capecitabine in Treating Patients With Neuroendocrine Carcinoma of the Gastrointestinal Tract or Pancreas That Is Metastatic or Cannot Be Removed by Surgery

Pancreatic Neuroendocrine Carcinoma Clinical Trial

Official title:

Randomized Phase II Study of Cisplatin and Etoposide Versus Temozolomide and Capecitabine in Patients With Advanced G3 Non-small Cell Gastroenteropancreatic Neuroendocrine Carcinomas

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02595424
• Other study ID #: EA2142
• Secondary ID: NCI-2015-00547NC
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 6, 2016
• Est. completion date: January 1, 2029

Study information

• Verified date: January 2024
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase II trial studies how well temozolomide and capecitabine work compared to standard treatment with cisplatin or carboplatin and etoposide in treating patients with neuroendocrine carcinoma of the gastrointestinal tract or pancreas that has spread to other parts of the body (metastatic) or cannot be removed by surgery. Drugs used in chemotherapy, such as temozolomide, capecitabine, cisplatin, carboplatin and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Certain types of neuroendocrine carcinomas may respond better to treatments other than the current standard treatment of cisplatin and etoposide. It is not yet known whether temozolomide and capecitabine may work better than cisplatin or carboplatin and etoposide in treating patients with this type of neuroendocrine carcinoma, called non-small cell neuroendocrine carcinoma.

Description:

PRIMARY OBJECTIVES:

I. To assess the progression free survival (PFS) of platinum (cisplatin or carboplatin) and etoposide versus the PFS of temozolomide and capecitabine in patients with advanced G3 non-small cell gastroenteropancreatic neuroendocrine carcinomas.

SECONDARY OBJECTIVES:

I. To assess the response rate (RR) of platinum (cisplatin or carboplatin) and etoposide versus the RR of temozolomide and capecitabine in patients with advanced G3 non-small cell gastroenteropancreatic neuroendocrine carcinomas.

II. To assess the overall survival (OS) of platinum (cisplatin or carboplatin) and etoposide versus the OS of temozolomide and capecitabine in patients with advanced G3 non-small cell gastroenteropancreatic neuroendocrine carcinomas.

III. To evaluate the toxicities associated with the combination of temozolomide and capecitabine and the combination of platinum (cisplatin or carboplatin) and etoposide, respectively, in patients with advanced G3 non-small cell gastroenteropancreatic neuroendocrine carcinomas.

TERTIARY OBJECTIVES:

I. To assess the impact of each treatment regimen on PFS, RR and OS based on marker of proliferation Ki-67 index in patients with advanced G3 non-small cell gastroenteropancreatic neuroendocrine carcinomas. (Laboratory) II. To assess the prognostic significance of well differentiated versus poorly differentiated non-small cell gastroenteropancreatic neuroendocrine tumors in relationship to survival and response to treatment. (Laboratory) III. To assess the agreement in Ki-67 status between that reported by institutional pathologist and that reported by central pathology review. (Laboratory)

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

ARM A: Patients receive capecitabine orally (PO) twice daily (BID) on days 1-14 and temozolomide PO once daily (QD) on days 10-14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive cisplatin intravenously (IV) on days 1-3 or carboplatin IV on day 1. Patients also receive etoposide IV on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 67
• Est. completion date: January 1, 2029
• Est. primary completion date: January 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have a locally advanced and unresectable or metastatic gastroenteropancreatic neuroendocrine carcinoma that is either known or suspected to be of gastrointestinal (GI) origin; primary tumors arising from the lung, gynecologic organs or prostate are not permitted

• Patients must have pathologically/histologically confirmed tumor of non-small cell histology

• Patients must have a Ki-67 proliferative index of 20-100% OR at least 10 mitotic figures per 10 high powered fields

• Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria; baseline measurements and evaluations of all sites of disease must be obtained within 4 weeks prior to randomization and must be acquired by multiphasic computed tomography (CT) or contrast magnetic resonance imaging (MRI)

• NOTE: positron emission tomography (PET)-CT scans are allowed provided the CT portion of the exam is equivalent to a diagnostic CT scan and includes both oral and IV contrast

• Patients may not have had any prior systemic treatment for this malignancy (for example chemotherapy or somatostatin analogues); prior palliative radiation is permitted but radiated lesions may not be used for measurement

• Patients may not have received any of the protocol agents within 5 years prior to randomization

• Any prior surgeries must have been completed at least 4 weeks prior to randomization

• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

• Patients may not be receiving any other investigational agents while on study treatment

• Patients may not be receiving Coumadin while on treatment; other anticoagulants are allowed

• Leukocytes >= 3,000/mm^3

• Absolute neutrophil count >= 1,500/mm^3

• Hemoglobin >= 9 g/dL

• Platelets >= 100,000/mm^3

• Total bilirubin =< institutional upper limit of normal (ULN) or =< 1.5 X institutional ULN (if the patient has liver metastases)

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional ULN or (=< 5 X institutional ULN if the patient has liver metastases)

• Serum creatinine =< 1.5 X institutional ULN and creatinine clearance >= 60 ml/min

• NOTE: creatinine clearance must be calculated using the Cockcroft-Gault equation

• Patients must have a life expectancy of >= 12 weeks as determined clinically by the treating physician

• Patients with brain metastases (either remote or current) or presence of carcinomatous meningitis are not eligible

• Patients with known dihydropyrimidine dehydrogenase (DPD) deficiency will be excluded

• Patients must NOT have active or uncontrolled infection, symptomatic heart failure, unstable angina pectoris, cardiac arrhythmia or a serious psychiatric illness/social situation that would limit compliance with study requirements

• Patients with impaired decision making capacity may participate in the study if a legal authorized representative is available to consent

• Patients must NOT have a history of allergic reactions attributed to compounds of similar chemical or biochemical composition to cisplatin, carboplatin, etoposide, temozolomide or capecitabine

• Patients must NOT have absorption issues that would limit the ability to absorb study agents

• Patients with a history of the following within =< 12 months of study entry are not eligible:

• Arterial thromboembolic events

• Unstable angina

• Myocardial Infarction

• Patients with symptomatic peripheral vascular disease are not eligible

• Patients must NOT have previous or concurrent malignancy; exceptions are made for patients who meet any of the following conditions:

• Non-melanoma skin cancer, in situ cervical cancer, superficial bladder cancer, or breast cancer in situ OR

• Prior malignancy completely excised or removed and patient has been continuously disease free for > 5 years OR

• Prior malignancy cured by non-surgical modalities and patient has been continuously disease free for > 5 years

• Women must not be pregnant or breast-feeding

• All females of childbearing potential must have a blood test or urine study within 2 weeks prior to randomization to rule out pregnancy

• A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)

• Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for the duration of their participation in the study

• Patients must be able to swallow pills

• Patients must be able to tolerate CT or magnetic resonance (MR) imaging including contrast agents as required for the treatment and the protocol

• Patients who are known to have human immunodeficiency virus (HIV) or are on combination antiretroviral therapy are ineligible

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Islet Cell
• Carcinoma, Neuroendocrine
• Gastric Neuroendocrine Carcinoma
• Intestinal Neuroendocrine Carcinoma
• Pancreatic Neuroendocrine Carcinoma

Intervention

Drug:
• Capecitabine
Given PO
• Carboplatin
Given IV
• Cisplatin
Given IV
• Etoposide
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Temozolomide
Given PO

Locations

Country	Name	City	State
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Christus Saint Frances Cabrini Hospital	Alexandria	Louisiana
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
United States	Mary Greeley Medical Center	Ames	Iowa
United States	McFarland Clinic PC - Ames	Ames	Iowa
United States	Community Hospital of Anaconda	Anaconda	Montana
United States	AnMed Health Cancer Center	Anderson	South Carolina
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Kaiser Permanente-Deer Valley Medical Center	Antioch	California
United States	Mission Hope Medical Oncology - Arroyo Grande	Arroyo Grande	California
United States	PCR Oncology	Arroyo Grande	California
United States	AdventHealth Infusion Center Asheville	Asheville	North Carolina
United States	Emory Saint Joseph's Hospital	Atlanta	Georgia
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Grady Health System	Atlanta	Georgia
United States	Sutter Auburn Faith Hospital	Auburn	California
United States	Sutter Cancer Centers Radiation Oncology Services-Auburn	Auburn	California
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	University of Colorado Hospital	Aurora	Colorado
United States	Saint Alphonsus Medical Center-Baker City	Baker City	Oregon
United States	Saint Louis Cancer and Breast Institute-Ballwin	Ballwin	Missouri
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	Flaget Memorial Hospital	Bardstown	Kentucky
United States	Medical Center of Baton Rouge	Baton Rouge	Louisiana
United States	Ochsner Health Center-Summa	Baton Rouge	Louisiana
United States	Ochsner High Grove	Baton Rouge	Louisiana
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	UHHS-Chagrin Highlands Medical Center	Beachwood	Ohio
United States	UPMC-Heritage Valley Health System Beaver	Beaver	Pennsylvania
United States	Indu and Raj Soin Medical Center	Beavercreek	Ohio
United States	Overlake Medical Center	Bellevue	Washington
United States	Strecker Cancer Center-Belpre	Belpre	Ohio
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Joseph Medical Center	Bloomington	Illinois
United States	Saint Elizabeth Boardman Hospital	Boardman	Ohio
United States	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Central Care Cancer Center - Bolivar	Bolivar	Missouri
United States	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri
United States	McFarland Clinic PC-Boone	Boone	Iowa
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Cox Cancer Center Branson	Branson	Missouri
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Harrison Medical Center	Bremerton	Washington
United States	Saint Joseph Mercy Brighton	Brighton	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Brighton	Brighton	Michigan
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Montefiore Medical Center-Einstein Campus	Bronx	New York
United States	Montefiore Medical Center-Weiler Hospital	Bronx	New York
United States	Henry Ford Cancer Institute-Downriver	Brownstown	Michigan
United States	Saint Joseph Regional Cancer Center	Bryan	Texas
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Mills-Peninsula Medical Center	Burlingame	California
United States	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Minnesota Oncology - Burnsville	Burnsville	Minnesota
United States	Loyola Center for Health at Burr Ridge	Burr Ridge	Illinois
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho
United States	Cambridge Medical Center	Cambridge	Minnesota
United States	Sutter Cancer Centers Radiation Oncology Services-Cameron Park	Cameron Park	California
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Joseph Mercy Canton	Canton	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Canton	Canton	Michigan
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Memorial Hospital of Carbondale	Carbondale	Illinois
United States	Caro Cancer Center	Caro	Michigan
United States	Carson Tahoe Regional Medical Center	Carson City	Nevada
United States	SIH Cancer Institute	Carterville	Illinois
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Duke Cancer Institute Cary	Cary	North Carolina
United States	Eden Hospital Medical Center	Castro Valley	California
United States	Dayton Physicians LLC-Miami Valley South	Centerville	Ohio
United States	Miami Valley Hospital South	Centerville	Ohio
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Christiana Care Health System-Concord Health Center	Chadds Ford	Pennsylvania
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	Geauga Hospital	Chardon	Ohio
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Memorial Hospital	Chattanooga	Tennessee
United States	Saint Joseph Mercy Chelsea	Chelsea	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital	Chelsea	Michigan
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Anderson	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Blue Ash	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Eden Park	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Kenwood	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Mercy West	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Anderson	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Westside	Cincinnati	Ohio
United States	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio
United States	Hematology Oncology Consultants-Clarkston	Clarkston	Michigan
United States	Newland Medical Associates-Clarkston	Clarkston	Michigan
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Southeastern Medical Oncology Center-Clinton	Clinton	North Carolina
United States	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	AdventHealth Infusion Center Haywood	Clyde	North Carolina
United States	Big Horn Basin Cancer Center	Cody	Wyoming
United States	Billings Clinic-Cody	Cody	Wyoming
United States	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho
United States	Coffeyville Regional Medical Center	Coffeyville	Kansas
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado
United States	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	Mount Carmel East Hospital	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	The Mark H Zangmeister Center	Columbus	Ohio
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Commonwealth Cancer Center-Corbin	Corbin	Kentucky
United States	Alegent Health Mercy Hospital	Council Bluffs	Iowa
United States	Greater Regional Medical Center	Creston	Iowa
United States	Oncology Hematology Care Inc-Crestview	Crestview Hills	Kentucky
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	Parkland Memorial Hospital	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Carle on Vermilion	Danville	Illinois
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Sutter Davis Hospital	Davis	California
United States	Dayton Physician LLC-Miami Valley Hospital North	Dayton	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Miami Valley Hospital North	Dayton	Ohio
United States	Henry Ford Medical Center-Fairlane	Dearborn	Michigan
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Northwestern Medicine Cancer Center Kishwaukee	DeKalb	Illinois
United States	Delaware Health Center-Grady Cancer Center	Delaware	Ohio
United States	Delaware Radiation Oncology	Delaware	Ohio
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Porter Adventist Hospital	Denver	Colorado
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Illinois CancerCare-Dixon	Dixon	Illinois
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	Dublin Methodist Hospital	Dublin	Ohio
United States	Kaiser Permanente Dublin	Dublin	California
United States	Mercy Medical Center	Durango	Colorado
United States	Southwest Oncology PC	Durango	Colorado
United States	Duke University Medical Center	Durham	North Carolina
United States	Prisma Health Cancer Institute - Easley	Easley	South Carolina
United States	Great Lakes Cancer Management Specialists-Doctors Park	East China Township	Michigan
United States	Pocono Medical Center	East Stroudsburg	Pennsylvania
United States	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Mercy Cancer Center-Elyria	Elyria	Ohio
United States	Walter Knox Memorial Hospital	Emmett	Idaho
United States	Saint Elizabeth Hospital	Enumclaw	Washington
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Deaconess Clinic Downtown	Evansville	Indiana
United States	Oncology Hematology Care Inc-Healthplex	Fairfield	Ohio
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Clinic North-Fargo	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Sanford South University Medical Center	Fargo	North Dakota
United States	Farmington Health Center	Farmington	Utah
United States	Parkland Health Center - Farmington	Farmington	Missouri
United States	Weisberg Cancer Treatment Center	Farmington Hills	Michigan
United States	Saint Francis Hospital	Federal Way	Washington
United States	Armes Family Cancer Center	Findlay	Ohio
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Orion Cancer Care	Findlay	Ohio
United States	Genesee Cancer and Blood Disease Treatment Center	Flint	Michigan
United States	Genesee Hematology Oncology PC	Flint	Michigan
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Aurora Health Center-Fond du Lac	Fond Du Lac	Wisconsin
United States	McFarland Clinic PC-Trinity Cancer Center	Fort Dodge	Iowa
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Mercy Hospital Fort Smith	Fort Smith	Arkansas
United States	UT Southwestern/Simmons Cancer Center-Fort Worth	Fort Worth	Texas
United States	Beebe South Coastal Health Campus	Frankford	Delaware
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Dayton Physicians LLC-Atrium	Franklin	Ohio
United States	Kaiser Permanente-Fremont	Fremont	California
United States	Palo Alto Medical Foundation-Fremont	Fremont	California
United States	Kaiser Permanente-Fresno	Fresno	California
United States	Unity Hospital	Fridley	Minnesota
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	Central Care Cancer Center - Garden City	Garden City	Kansas
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	Aurora Health Care Germantown Health Center	Germantown	Wisconsin
United States	Mountain Blue Cancer Care Center	Golden	Colorado
United States	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Aurora Cancer Care-Grafton	Grafton	Wisconsin
United States	CHI Health Saint Francis	Grand Island	Nebraska
United States	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Trinity Health Grand Rapids Hospital	Grand Rapids	Michigan
United States	Central Care Cancer Center - Great Bend	Great Bend	Kansas
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	UPMC Cancer Centers - Arnold Palmer Pavilion	Greensburg	Pennsylvania
United States	Dayton Physicians LLC-Wayne	Greenville	Ohio
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	Wayne Hospital	Greenville	Ohio
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	Academic Hematology Oncology Specialists	Grosse Pointe Woods	Michigan
United States	Great Lakes Cancer Management Specialists-Van Elslander Cancer Center	Grosse Pointe Woods	Michigan
United States	Michigan Breast Specialists-Grosse Pointe Woods	Grosse Pointe Woods	Michigan
United States	Mount Carmel Grove City Hospital	Grove City	Ohio
United States	HaysMed University of Kansas Health System	Hays	Kansas
United States	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania
United States	Lehigh Valley Hospital-Hazleton	Hazleton	Pennsylvania
United States	Saint Peter's Community Hospital	Helena	Montana
United States	Cancer and Blood Specialists-Henderson	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada - Henderson	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada-Horizon Ridge	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada-Southeast Henderson	Henderson	Nevada
United States	GenesisCare USA - Henderson	Henderson	Nevada
United States	Las Vegas Cancer Center-Henderson	Henderson	Nevada
United States	Las Vegas Urology - Green Valley	Henderson	Nevada
United States	Las Vegas Urology - Pebble	Henderson	Nevada
United States	OptumCare Cancer Care at Seven Hills	Henderson	Nevada
United States	Urology Specialists of Nevada - Green Valley	Henderson	Nevada
United States	AdventHealth Hendersonville	Hendersonville	North Carolina
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	Pulmonary Medicine Center of Chattanooga-Hixson	Hixson	Tennessee
United States	Loyola Medicine Homer Glen	Homer Glen	Illinois
United States	Kaiser Permanente Moanalua Medical Center	Honolulu	Hawaii
United States	CHI Saint Vincent Cancer Center Hot Springs	Hot Springs	Arkansas
United States	Houston Methodist Hospital	Houston	Texas
United States	Methodist Willowbrook Hospital	Houston	Texas
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Centerpoint Medical Center LLC	Independence	Missouri
United States	Cleveland Clinic Cancer Center Independence	Independence	Ohio
United States	Allegiance Health	Jackson	Michigan
United States	Onslow Memorial Hospital	Jacksonville	North Carolina
United States	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina
United States	McFarland Clinic PC-Jefferson	Jefferson	Iowa
United States	Capital Region Southwest Campus	Jefferson City	Missouri
United States	Emory Johns Creek Hospital	Johns Creek	Georgia
United States	UW Cancer Center Johnson Creek	Johnson Creek	Wisconsin
United States	UPMC-Johnstown/John P. Murtha Regional Cancer Center	Johnstown	Pennsylvania
United States	Freeman Health System	Joplin	Missouri
United States	Mercy Hospital Joplin	Joplin	Missouri
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Research Medical Center	Kansas City	Missouri
United States	Truman Medical Centers	Kansas City	Missouri
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	University of Kansas Cancer Center - North	Kansas City	Missouri
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Heartland Hematology and Oncology	Kearney	Nebraska
United States	Ochsner Medical Center Kenner	Kenner	Louisiana
United States	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin
United States	First Dayton Cancer Care	Kettering	Ohio
United States	Greater Dayton Cancer Center	Kettering	Ohio
United States	Kettering Medical Center	Kettering	Ohio
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Cancer Center of Kansas-Kingman	Kingman	Kansas
United States	Kingman Regional Medical Center	Kingman	Arizona
United States	Marshfield Clinic - Ladysmith Center	Ladysmith	Wisconsin
United States	CHRISTUS Lake Charles Medical Center	Lake Charles	Louisiana
United States	Northwestern Medicine Lake Forest Hospital	Lake Forest	Illinois
United States	Rocky Mountain Cancer Centers-Lakewood	Lakewood	Colorado
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Saint Clare Hospital	Lakewood	Washington
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Sparrow Hospital	Lansing	Michigan
United States	Alliance for Childhood Diseases/Cure 4 the Kids Foundation	Las Vegas	Nevada
United States	Ann M Wierman MD LTD	Las Vegas	Nevada
United States	Cancer and Blood Specialists-Shadow	Las Vegas	Nevada
United States	Cancer and Blood Specialists-Tenaya	Las Vegas	Nevada
United States	Cancer Therapy and Integrative Medicine	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Northwest	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Town Center	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada-Summerlin	Las Vegas	Nevada
United States	Desert West Surgery	Las Vegas	Nevada
United States	GenesisCare USA - Fort Apache	Las Vegas	Nevada
United States	GenesisCare USA - Las Vegas	Las Vegas	Nevada
United States	GenesisCare USA - Vegas Tenaya	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-San Martin	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Tenaya	Las Vegas	Nevada
United States	Hope Cancer Care of Nevada	Las Vegas	Nevada
United States	Las Vegas Cancer Center-Medical Center	Las Vegas	Nevada
United States	Las Vegas Prostate Cancer Center	Las Vegas	Nevada
United States	Las Vegas Urology - Cathedral Rock	Las Vegas	Nevada
United States	Las Vegas Urology - Pecos	Las Vegas	Nevada
United States	Las Vegas Urology - Smoke Ranch	Las Vegas	Nevada
United States	Las Vegas Urology - Sunset	Las Vegas	Nevada
United States	OptumCare Cancer Care at Charleston	Las Vegas	Nevada
United States	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada
United States	OptumCare Cancer Care at MountainView	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada
United States	Summerlin Hospital Medical Center	Las Vegas	Nevada
United States	Sunrise Hospital and Medical Center	Las Vegas	Nevada
United States	University Cancer Center	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Urology Specialists of Nevada - Central	Las Vegas	Nevada
United States	Urology Specialists of Nevada - Northwest	Las Vegas	Nevada
United States	Urology Specialists of Nevada - Southwest	Las Vegas	Nevada
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Cancer Centers of Southwest Oklahoma Research	Lawton	Oklahoma
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	University of Kansas Cancer Center - Lee's Summit	Lee's Summit	Missouri
United States	Kansas Institute of Medicine Cancer and Blood Center	Lenexa	Kansas
United States	Minimally Invasive Surgery Hospital	Lenexa	Kansas
United States	Beebe Medical Center	Lewes	Delaware
United States	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania
United States	Lewistown Hospital	Lewistown	Pennsylvania
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	Cancer Center of Kansas-Liberal	Liberal	Kansas
United States	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Hope Cancer Clinic	Livonia	Michigan
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Saint Joseph London	London	Kentucky
United States	Longmont United Hospital	Longmont	Colorado
United States	Rocky Mountain Cancer Centers-Longmont	Longmont	Colorado
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Los Angeles County-USC Medical Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Jewish Hospital	Louisville	Kentucky
United States	Saints Mary and Elizabeth Hospital	Louisville	Kentucky
United States	UofL Health Medical Center Northeast	Louisville	Kentucky
United States	Great Lakes Cancer Management Specialists-Macomb Medical Campus	Macomb	Michigan
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Michigan Breast Specialists-Macomb Township	Macomb	Michigan
United States	Medical Center of Central Georgia	Macon	Georgia
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	Cancer Center of Kansas-Manhattan	Manhattan	Kansas
United States	OhioHealth Mansfield Hospital	Mansfield	Ohio
United States	Fairview Clinics and Surgery Center Maple Grove	Maple Grove	Minnesota
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	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin
United States	Bay Area Medical Center	Marinette	Wisconsin
United States	OhioHealth Marion General Hospital	Marion	Ohio
United States	Saint Mary's Oncology/Hematology Associates of Marlette	Marlette	Michigan
United States	McFarland Clinic PC-Marshalltown	Marshalltown	Iowa
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	UH Seidman Cancer Center at Landerbrook Health Center	Mayfield Heights	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	UPMC Cancer Center at UPMC McKeesport	McKeesport	Pennsylvania
United States	Cancer Center of Kansas - McPherson	McPherson	Kansas
United States	Marjorie Weinberg Cancer Center at Loyola-Gottlieb	Melrose Park	Illinois
United States	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio
United States	Idaho Urologic Institute-Meridian	Meridian	Idaho
United States	Franciscan Saint Anthony Health-Michigan City	Michigan City	Indiana
United States	Woodland Cancer Care Center	Michigan City	Indiana
United States	UH Seidman Cancer Center at Southwest General Hospital	Middleburg Heights	Ohio
United States	Dayton Physicians LLC-Signal Point	Middletown	Ohio
United States	Aurora Cancer Care-Milwaukee	Milwaukee	Wisconsin
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Aurora Sinai Medical Center	Milwaukee	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Health Partners Inc	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Community Medical Hospital	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Kaiser Permanente-Modesto	Modesto	California
United States	Memorial Medical Center	Modesto	California
United States	Monroe Cancer Center	Monroe	Michigan
United States	Ochsner LSU Health Monroe Medical Center	Monroe	Louisiana
United States	Monticello Cancer Center	Monticello	Minnesota
United States	UPMC Hillman Cancer Center in Coraopolis	Moon	Pennsylvania
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	Palo Alto Medical Foundation-Camino Division	Mountain View	California
United States	Palo Alto Medical Foundation-Gynecologic Oncology	Mountain View	California
United States	Inspira Medical Center Mullica Hill	Mullica Hill	New Jersey
United States	Trinity Health Muskegon Hospital	Muskegon	Michigan
United States	Saint Alphonsus Cancer Care Center-Nampa	Nampa	Idaho
United States	UC Comprehensive Cancer Center at Silver Cross	New Lenox	Illinois
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	Cancer Center of Western Wisconsin	New Richmond	Wisconsin
United States	New Ulm Medical Center	New Ulm	Minnesota
United States	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Christiana Gynecologic Oncology LLC	Newark	Delaware
United States	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Licking Memorial Hospital	Newark	Ohio
United States	Medical Oncology Hematology Consultants PA	Newark	Delaware
United States	Newark Radiation Oncology	Newark	Ohio
United States	Chancellor Center for Oncology	Newburgh	Indiana
United States	USC Norris Oncology/Hematology-Newport Beach	Newport Beach	California
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	Lakeland Hospital Niles	Niles	Michigan
United States	Cancer and Hematology Centers of Western Michigan - Norton Shores	Norton Shores	Michigan
United States	Sutter Cancer Research Consortium	Novato	California
United States	Henry Ford Medical Center-Columbus	Novi	Michigan
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	Kaiser Permanente-Oakland	Oakland	California
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Olathe Health Cancer Center	Olathe	Kansas
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Immanuel Medical Center	Omaha	Nebraska
United States	Alegent Health Lakeside Hospital	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Hematology and Oncology Consultants PC	Omaha	Nebraska
United States	Saint Alphonsus Medical Center-Ontario	Ontario	Oregon
United States	Memorial GYN Plus	Ooltewah	Tennessee
United States	University of Chicago Medicine-Orland Park	Orland Park	Illinois
United States	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Radiation Oncology of Northern Illinois	Ottawa	Illinois
United States	Menorah Medical Center	Overland Park	Kansas
United States	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas
United States	Hope Cancer Care of Nevada-Pahrump	Pahrump	Nevada
United States	Palo Alto Medical Foundation Health Care	Palo Alto	California
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	Midlands Community Hospital	Papillion	Nebraska
United States	Parker Adventist Hospital	Parker	Colorado
United States	Rocky Mountain Cancer Centers-Parker	Parker	Colorado
United States	University Hospitals Parma Medical Center	Parma	Ohio
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Keck Medical Center of USC Pasadena	Pasadena	California
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Cancer Center at Saint Joseph's	Phoenix	Arizona
United States	Ascension Via Christi - Pittsburg	Pittsburg	Kansas
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	UPMC Jefferson Regional Radiation Oncology	Pittsburgh	Pennsylvania
United States	UPMC-Magee Womens Hospital	Pittsburgh	Pennsylvania
United States	UPMC-Passavant Hospital	Pittsburgh	Pennsylvania
United States	UPMC-Presbyterian Hospital	Pittsburgh	Pennsylvania
United States	UPMC-Saint Clair Hospital Cancer Center	Pittsburgh	Pennsylvania
United States	UPMC-Saint Margaret	Pittsburgh	Pennsylvania
United States	UPMC-Shadyside Hospital	Pittsburgh	Pennsylvania
United States	21st Century Oncology-Pontiac	Pontiac	Michigan
United States	Hope Cancer Center	Pontiac	Michigan
United States	Newland Medical Associates-Pontiac	Pontiac	Michigan
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Huron Medical Center PC	Port Huron	Michigan
United States	Lake Huron Medical Center	Port Huron	Michigan
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Geisinger Cancer Services-Pottsville	Pottsville	Pennsylvania
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington
United States	Cancer Center of Kansas - Pratt	Pratt	Kansas
United States	Fairview Northland Medical Center	Princeton	Minnesota
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Rocky Mountain Cancer Centers - Pueblo	Pueblo	Colorado
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Aurora Cancer Care-Racine	Racine	Wisconsin
United States	Duke Raleigh Hospital	Raleigh	North Carolina
United States	Eisenhower Medical Center	Rancho Mirage	California
United States	Northwest Hospital Center	Randallstown	Maryland
United States	Kaiser Permanente-Redwood City	Redwood City	California
United States	Spectrum Health Reed City Hospital	Reed City	Michigan
United States	Beebe Health Campus	Rehoboth Beach	Delaware
United States	Radiation Oncology Associates	Reno	Nevada
United States	Renown Regional Medical Center	Reno	Nevada
United States	Saint Mary's Regional Medical Center	Reno	Nevada
United States	Valley Medical Center	Renton	Washington
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	UT Southwestern Clinical Center at Richardson/Plano	Richardson	Texas
United States	Kaiser Permanente-Richmond	Richmond	California
United States	Reid Health	Richmond	Indiana
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	Great Lakes Cancer Management Specialists-Rochester Hills	Rochester Hills	Michigan
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Kaiser Permanente-Roseville	Roseville	California
United States	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California
United States	Sutter Roseville Medical Center	Roseville	California
United States	Kaiser Permanente - Sacramento	Sacramento	California
United States	Kaiser Permanente Downtown Commons	Sacramento	California
United States	Kaiser Permanente-South Sacramento	Sacramento	California
United States	Sutter Medical Center Sacramento	Sacramento	California
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Oncology Hematology Associates of Saginaw Valley PC	Saginaw	Michigan
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan
United States	Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Mercy Hospital South	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Siteman Cancer Center at Christian Hospital	Saint Louis	Missouri
United States	Siteman Cancer Center-South County	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
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	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	Salina Regional Health Center	Salina	Kansas
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	University of Utah Sugarhouse Health Center	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
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-Mission Bay	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	Pacific Central Coast Health Center-San Luis Obispo	San Luis Obispo	California
United States	Kaiser Permanente-San Rafael	San Rafael	California
United States	Kaiser San Rafael-Gallinas	San Rafael	California
United States	Kootenai Cancer Clinic	Sandpoint	Idaho
United States	North Coast Cancer Care	Sandusky	Ohio
United States	UH Seidman Cancer Center at Firelands Regional Medical Center	Sandusky	Ohio
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Palo Alto Medical Foundation-Santa Cruz	Santa Cruz	California
United States	Mission Hope Medical Oncology - Santa Maria	Santa Maria	California
United States	Kaiser Permanente-Santa Rosa	Santa Rosa	California
United States	Sutter Pacific Medical Foundation	Santa Rosa	California
United States	Community Medical Center	Scranton	Pennsylvania
United States	TidalHealth Nanticoke / Allen Cancer Center	Seaford	Delaware
United States	Geisinger Medical Oncology-Selinsgrove	Selinsgrove	Pennsylvania
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	UPMC Cancer Center at UPMC Northwest	Seneca	Pennsylvania
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin
United States	Henry Ford Macomb Health Center - Shelby Township	Shelby	Michigan
United States	Jewish Hospital Medical Center South	Shepherdsville	Kentucky
United States	Welch Cancer Center	Sheridan	Wyoming
United States	LSU Health Sciences Center at Shreveport	Shreveport	Louisiana
United States	Dayton Physicians LLC-Wilson	Sidney	Ohio
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Kaiser Permanente-South San Francisco	South San Francisco	California
United States	Central Illinois Hematology Oncology Center	Springfield	Illinois
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Mercy Medical Center	Springfield	Massachusetts
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Springfield Regional Cancer Center	Springfield	Ohio
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Geisinger Medical Group	State College	Pennsylvania
United States	Bhadresh Nayak MD PC-Sterling Heights	Sterling Heights	Michigan
United States	Ascension Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Kaiser Permanente-Stockton	Stockton	California
United States	Cleveland Clinic Cancer Center Strongsville	Strongsville	Ohio
United States	Houston Methodist Sugar Land Hospital	Sugar Land	Texas
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	Aurora Medical Center in Summit	Summit	Wisconsin
United States	Palo Alto Medical Foundation-Sunnyvale	Sunnyvale	California
United States	Missouri Baptist Outpatient Center-Sunset Hills	Sunset Hills	Missouri
United States	Southwest Illinois Health Services LLP	Swansea	Illinois
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	Franciscan Research Center-Northwest Medical Plaza	Tacoma	Washington
United States	Northwest Medical Specialties PLLC	Tacoma	Washington
United States	Ascension Saint Joseph Hospital	Tawas City	Michigan
United States	Sanford Thief River Falls Medical Center	Thief River Falls	Minnesota
United States	Rocky Mountain Cancer Centers-Thornton	Thornton	Colorado
United States	ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital	Toledo	Ohio
United States	University of Kansas Health System Saint Francis Campus	Topeka	Kansas
United States	Munson Medical Center	Traverse City	Michigan
United States	Dayton Physicians LLC - Troy	Troy	Ohio
United States	Upper Valley Medical Center	Troy	Ohio
United States	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin
United States	UPMC Uniontown Hospital Radiation Oncology	Uniontown	Pennsylvania
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	Kaiser Permanente Medical Center-Vacaville	Vacaville	California
United States	Sutter Cancer Centers Radiation Oncology Services-Vacaville	Vacaville	California
United States	Kaiser Permanente-Vallejo	Vallejo	California
United States	Sutter Solano Medical Center/Cancer Center	Vallejo	California
United States	Inspira Medical Center Vineland	Vineland	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	University Hospitals Sharon Health Center	Wadsworth	Ohio
United States	Kaiser Permanente-Walnut Creek	Walnut Creek	California
United States	Advanced Breast Care Center PLLC	Warren	Michigan
United States	Great Lakes Cancer Management Specialists-Macomb Professional Building	Warren	Michigan
United States	Macomb Hematology Oncology PC	Warren	Michigan
United States	Michigan Breast Specialists-Warren	Warren	Michigan
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Saint Joseph Warren Hospital	Warren	Ohio
United States	South Pointe Hospital	Warrensville Heights	Ohio
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	Marion L Shepard Cancer Center at Vidant Beaufort Hospital	Washington	North Carolina
United States	MedStar Washington Hospital Center	Washington	District of Columbia
United States	Mercy Hospital Washington	Washington	Missouri
United States	Sibley Memorial Hospital	Washington	District of Columbia
United States	UPMC Washington Hospital Radiation Oncology	Washington	Pennsylvania
United States	Aurora Cancer Care-Waukesha	Waukesha	Wisconsin
United States	Marshfield Clinic-Wausau Center	Wausau	Wisconsin
United States	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Aurora West Allis Medical Center	West Allis	Wisconsin
United States	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan
United States	Saint Mary's Oncology/Hematology Associates of West Branch	West Branch	Michigan
United States	University of Cincinnati Cancer Center-West Chester	West Chester	Ohio
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Saint Ann's Hospital	Westerville	Ohio
United States	UH Seidman Cancer Center at Saint John Medical Center	Westlake	Ohio
United States	UHHS-Westlake Medical Center	Westlake	Ohio
United States	William E Kahlert Regional Cancer Center/Sinai Hospital	Westminster	Maryland
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas
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	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Christiana Care Health System-Wilmington Hospital	Wilmington	Delaware
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Cleveland Clinic Wooster Family Health and Surgery Center	Wooster	Ohio
United States	Sanford Cancer Center Worthington	Worthington	Minnesota
United States	Fairview Lakes Medical Center	Wyoming	Minnesota
United States	Metro Health Hospital	Wyoming	Michigan
United States	Rush-Copley Healthcare Center	Yorkville	Illinois
United States	Saint Elizabeth Youngstown Hospital	Youngstown	Ohio
United States	Huron Gastroenterology PC	Ypsilanti	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus	Ypsilanti	Michigan
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
ECOG-ACRIN Cancer Research Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Ki-67 as a continuous measure assessed by immunohistochemistry (IHC)	Will evaluate the interaction, if any, between Ki-67 as a continuous measure and treatment. Cox regression of logistic regression, as appropriate, will be used to identify whether the treatment effect varies by Ki-67 for PFS, OS, and RR.	Baseline
Other	Ki-67 measured centrally	Concordance between Ki-67 measured centrally versus registering institutions? pathology assessments will be investigated and reported. Intra-class correlation will be calculated to assess agreement amongst the two continuous measures.	Baseline
Other	Ki-67 measured with registering institutions? pathology assessments	Concordance between Ki-67 measured centrally versus registering institutions? pathology assessments will be investigated and reported. Intra-class correlation will be calculated to assess agreement amongst the two continuous measures.	Baseline
Other	Optimal cutoff value in Ki-67 that defines patients with prolonged OS assessed by IHC	Receiver operating characteristics analysis will be performed to first determine the optimal cutoff value in Ki-67 that defines patients with prolonged OS. For the series of Ki-67 values observed in the data, Youden?s index will be calculated and with the highest index the threshold that minimizes the false positive and false negative rates for best detecting prolonged OS will be identified. Optimal cutoff values of Ki-67 with respect to response to temozolomide and capecitabine, positive octreotide scans, and negative PET scans will also be determined in a similar manner.	Baseline
Other	Prognostic significance of poorly differentiated non-small cell gastroenteropancreatic neuroendocrine tumors	Will assess the prognostic significance of well differentiated versus poorly differentiated non-small cell gastroenteropancreatic neuroendocrine tumors in relationship to survival and response to treatment in a similar manner, via Cox proportional hazard models for time to event endpoint and logistic regression for objective response.	Baseline
Other	Prognostic significance of well differentiated non-small cell gastroenteropancreatic neuroendocrine tumors	Will assess the prognostic significance of well differentiated versus poorly differentiated non-small cell gastroenteropancreatic neuroendocrine tumors in relationship to survival and response to treatment in a similar manner, via Cox proportional hazard models for time to event endpoint and logistic regression for objective response.	Baseline
Primary	PFS	Kaplan-Meier estimates will be used for time-to-event distribution. PFS by arm will be compared using one-sided stratified log-rank tests. Stratified Cox?s proportional hazards models will be used to estimate hazard ratios.	Time from randomization to documented progression or death without progression, assessed up to 1 year
Secondary	Incidence of toxicity, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0	90% confidence intervals will be provided.	Up to 30 days after last dose of protocol therapy
Secondary	OS	Kaplan-Meier estimates will be used for time-to-event distribution. OS by arm will be compared using one-sided stratified log-rank tests. Stratified Cox?s proportional hazards models will be used to estimate hazard ratios.	Time from randomization to death from any cause, assessed up to 5 years
Secondary	Response rate (complete response or partial response) by RECIST 1.1	Analyzed using a Fisher?s exact test at a one-sided significance level of 0.10.	Up to 5 years