Temozolomide With or Without Capecitabine in Treating Patients With Advanced Pancreatic Neuroendocrine Tumors

Insulinoma Clinical Trial

Official title:

A Randomized Phase II Study of Temozolomide or Temozolomide and Capecitabine in Patients With Advanced Pancreatic Neuroendocrine Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01824875
• Other study ID #: E2211
• Secondary ID: NCI-2012-02007E2
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 8, 2013
• Est. completion date: December 2024

Study information

• Verified date: February 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 giving temozolomide with or without capecitabine works in treating patients with advanced pancreatic neuroendocrine tumors. Drugs used in chemotherapy, such as temozolomide and capecitabine, 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. It is not yet known whether temozolomide is more effective with or without capecitabine in treating patients with advanced pancreatic neuroendocrine tumors.

Description:

PRIMARY OBJECTIVES:

I. To evaluate progression-free survival (PFS) associated with temozolomide alone or temozolomide and capecitabine in patients with advanced pancreatic neuroendocrine tumors.

SECONDARY OBJECTIVES:

I. To evaluate response rates (RR) associated with temozolomide alone or temozolomide and capecitabine treatment in patients with advanced pancreatic neuroendocrine tumors.

II. To evaluate overall survival (OS) associated with temozolomide alone or temozolomide and capecitabine in patients with advanced pancreatic neuroendocrine tumors.

III. To evaluate the toxicity associated with temozolomide alone or temozolomide and capecitabine treatment in patients with advanced pancreatic neuroendocrine tumors.

IV. To evaluate the usefulness of methyl guanine methyltransferase (MGMT) status (by immunohistochemistry [IHC] and promoter methylation) for predicting response in pancreatic neuroendocrine tumor patients treated with either temozolomide or temozolomide and capecitabine.

V. To bank radiology images for evaluation of quality, reproducibility, and compliance with computed tomography (CT) methodology.

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

ARM A: Patients receive temozolomide orally (PO) once daily (QD) on days 1-5. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive capecitabine PO twice daily (BID) on days 1-14 and temozolomide PO QD on days 10-14. Treatment repeats every 28 days for up to 13 courses 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: 144
• Est. completion date: December 2024
• Est. primary completion date: May 26, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient must have histologically or pathologically confirmed locally unresectable or metastatic low or intermediate grade pancreatic neuroendocrine tumor

• Patient 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 <= 4 weeks prior to randomization and must be acquired by multiphasic CT or contrast magnetic resonance imaging (MRI)

• Date of last documented disease progression must be within 12 months from date of randomization

• Prior everolimus and/or sunitinib therapy is allowed, so long as it was discontinued >= 4 weeks prior to randomization

• Concurrent somatostatin analogues are allowed provided that patients

• Have been on a stable dose for 8 weeks and

• Have documented disease progression on that dose

• Chemoembolization is allowed if = 4 weeks from study entry. There are 2 possible scenarios:

• If patient has hepatic disease only: they need to have progressed in the liver since chemoembolization and have measurable disease by RECIST 1.1 in order to be eligible.

• If patient has hepatic and extrahepatic disease: they will need to have progressed inside OR outside the liver and have measureable disease by RECIST 1.1 in order to be eligible.

• 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]) <= 3 X institutional ULN or (<= 5 X institutional ULN if the patient has liver metastases)

• Serum creatinine <= 1.5 X institutional ULN

• Patient must have Eastern Cooperative Oncology Group (ECOG) performance status 0-1

• Patient must have life expectancy >= 12 weeks 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:

• Has not undergone a hysterectomy or bilateral oophorectomy; or

• 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; should a woman become pregnant while participating in this study, she should inform her treating physician immediately; if a man impregnates a woman while participating in this study, he should inform his treating physician immediately

• Patient must be able to swallow pills

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

Exclusion Criteria:

• Small cell carcinoma

• Prior temozolomide, dacarbazine (DTIC), or capecitabine, or 5-FU (fluorouracil) therapy

• Receiving any other investigational agents while on study treatment

• Receiving Coumadin while on treatment; other anticoagulants are allowed

• Patients with either clinically apparent central nervous system metastases or carcinomatous meningitis are ineligible

• Active or uncontrolled infection or serious medical or psychiatric illness

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or capecitabine

• Absorption issues that would limit the ability to absorb study agents

• Patients with a history of the following within 12 months of study entry:

• Arterial thromboembolic events

• Unstable angina

• Myocardial Infarction

• Symptomatic peripheral vascular disease

• Patients with previous or concurrent malignancy; exceptions are made for patients who meet any of the following conditions:

• Non-melanoma skin cancer, in situ cervical 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

• Pregnant or breast-feeding

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Islet Cell
• Gastrinoma
• Glucagonoma
• Insulinoma
• Islet Cell Carcinoma
• Neuroendocrine Tumors
• Pancreatic Polypeptide Tumor
• Recurrent Islet Cell Carcinoma
• Somatostatinoma

Intervention

Drug:
• temozolomide
Given PO
• capecitabine
Given PO

Locations

Country	Name	City	State
United States	Oncare Hawaii Inc-Pali Momi	'Aiea	Hawaii
United States	Pali Momi Medical Center	'Aiea	Hawaii
United States	Bixby Medical Center	Adrian	Michigan
United States	Hickman Cancer Center	Adrian	Michigan
United States	Akron General Medical Center	Akron	Ohio
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	Mary Greeley Medical Center	Ames	Iowa
United States	McFarland Clinic PC-William R Bliss Cancer Center	Ames	Iowa
United States	New York Oncology Hematology PC - Amsterdam	Amsterdam	New York
United States	Kaiser Anaheim Medical Center	Anaheim	California
United States	Michigan Cancer Research Consortium Community Clinical Oncology Program	Ann Arbor	Michigan
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	University of Michigan University Hospital	Ann Arbor	Michigan
United States	Kaiser Permanente-Deer Valley Medical Center	Antioch	California
United States	Kaiser Permanente Medical Group - Baldwin Park	Baldwin Park	California
United States	Ochsner Health Center-Summa	Baton Rouge	Louisiana
United States	Cleveland Clinic Cancer Center Beachwood	Beachwood	Ohio
United States	Kaiser Foundation Hospital	Bellflower	California
United States	Strecker Cancer Center-Belpre	Belpre	Ohio
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
United States	Constantinou, Costas L MD (UIA Investigator)	Bettendorf	Iowa
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Joseph Medical Center	Bloomington	Illinois
United States	Saint Alphonsus Regional Medical Center	Boise	Idaho
United States	Central Care Cancer Center-Carrie J Babb Cancer Center	Bolivar	Missouri
United States	McFarland Clinic PC-Boone	Boone	Iowa
United States	Boston Medical Center	Boston	Massachusetts
United States	Toledo Clinic Cancer Centers-Bowling Green	Bowling Green	Ohio
United States	CoxHealth Cancer Center	Branson	Missouri
United States	Montefiore Medical Center	Bronx	New York
United States	Montefiore Medical Center-Weiler Division	Bronx	New York
United States	Mills - Peninsula Hospitals	Burlingame	California
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Illinois CancerCare-Canton	Canton	Illinois
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	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	Northwestern University	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Oncology and Hematology Care Inc - Blue Ash	Cincinnati	Ohio
United States	Oncology and Hematology Care Incorporated	Cincinnati	Ohio
United States	Oncology Hematology Care Inc - Anderson	Cincinnati	Ohio
United States	Oncology Hematology Care Inc - Kenwood	Cincinnati	Ohio
United States	Oncology Hematology Care Inc - Western Hills	Cincinnati	Ohio
United States	University of Cincinnati	Cincinnati	Ohio
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Columbus CCOP	Columbus	Ohio
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 Health Center West	Columbus	Ohio
United States	Ohio State University Medical 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	Oncology Hematology Care Incorporated	Crestview Hills	Kentucky
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Dayton CCOP	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	Samaritan North Health Center	Dayton	Ohio
United States	Oakwood Hospital	Dearborn	Michigan
United States	Cancer Care Center of Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	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	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Iowa Oncology Research Association CCOP	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	Saint John Hospital and Medical Center	Detroit	Michigan
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	Fairview-Southdale Hospital	Edina	Minnesota
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Hematology Oncology Center Incorporated	Elyria	Ohio
United States	Mercy Cancer Center-Elyria	Elyria	Ohio
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Oncology Hematology Care Inc	Fairfield	Ohio
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Kaiser Permanente Hospital	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	California
United States	Unity Hospital	Fridley	Minnesota
United States	Illinois CancerCare Galesburg	Galesburg	Illinois
United States	Illinois CancerCare-Galesburg Cottage Plaza Office	Galesburg	Illinois
United States	Greenville Health System Cancer Institute-Butternut	Greenville	South Carolina
United States	Greenville Health System Cancer Institute/Greenville CCOP	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Greenville Health System Cancer Institute-Greer	Greer	South Carolina
United States	Kaiser Permanente - Harbor City	Harbor City	California
United States	Saint Francis Hospital and Medical Center	Hartford	Connecticut
United States	Kaiser Permanente, Hayward	Hayward	California
United States	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	Hematology Oncology Associates of Illinois-Highland Park	Highland Park	Illinois
United States	Hinsdale Hematology Oncology Associates Incorporated	Hinsdale	Illinois
United States	Kaiser Permanente Moanalua Medical Center	Honolulu	Hawaii
United States	Oncare Hawaii Inc-Kuakini	Honolulu	Hawaii
United States	Oncare Hawaii Inc-POB II	Honolulu	Hawaii
United States	OnCare Hawaii-Liliha	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	University of Hawaii	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	Cleveland Clinic Cancer Center Independence	Independence	Ohio
United States	Franciscan Saint Francis Health-Indianapolis	Indianapolis	Indiana
United States	Southern California Permanente Medical Group	Irvine	California
United States	Allegiance Health	Jackson	Michigan
United States	Edna Williams Cancer Center at the Baptist Cancer Institute	Jacksonville	Florida
United States	McFarland Clinic PC-Jefferson	Jefferson	Iowa
United States	Capital Region Medical Center-Goldschmidt Cancer Center	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	Presence Saint Mary's Hospital	Kankakee	Illinois
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	Kinston Medical Specialists PA	Kinston	North Carolina
United States	Gundersen Lutheran	La Crosse	Wisconsin
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Lancaster Radiation Oncology	Lancaster	Ohio
United States	Sparrow Hospital	Lansing	Michigan
United States	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada
United States	New York Oncology Hematology PC - Latham	Latham	New York
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Beebe Medical Center	Lewes	Delaware
United States	Geisinger Medical Oncology at Evangelical Community Hospital	Lewisburg	Pennsylvania
United States	Cancer Center of Kansas-Liberal	Liberal	Kansas
United States	North Shore Hematology Oncology	Libertyville	Illinois
United States	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii
United States	Lima Memorial Hospital	Lima	Ohio
United States	Saint Rita's Medical Center	Lima	Ohio
United States	Saint Mary Mercy Hospital	Livonia	Michigan
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	University of Southern California/Norris Cancer Center	Los Angeles	California
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Cancer Center of Kansas-Manhattan	Manhattan	Kansas
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	McFarland Clinic PC-Marshalltown	Marshalltown	Iowa
United States	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio
United States	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	Cancer Center of Kansas - McPherson	McPherson	Kansas
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Middlesex Hospital	Middletown	Connecticut
United States	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Kaiser Permanente-Modesto	Modesto	California
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	Illinois CancerCare-Monmouth	Monmouth	Illinois
United States	Community Cancer Center of Monroe	Monroe	Michigan
United States	Mercy Memorial Hospital	Monroe	Michigan
United States	Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County	Mount Holly	New Jersey
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	Vanderbilt Cancer Center	Nashville	Tennessee
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	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	Regional Hematology and Oncology PA	Newark	Delaware
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	Illinois Cancer Specialists-Niles	Niles	Illinois
United States	Community Cancer Center Foundation	Normal	Illinois
United States	Sutter Cancer Research Consortium	Novato	California
United States	Kaiser Permanente-Oakland	Oakland	California
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	University of California Medical Center At Irvine-Orange Campus	Orange	California
United States	Saint Charles Hospital	Oregon	Ohio
United States	Toledo Clinic Cancer Centers-Oregon	Oregon	Ohio
United States	Florida Hospital	Orlando	Florida
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois
United States	Kaiser Permanente - Panorama City	Panorama City	California
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Pekin Cancer Treatment Center	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Illinois Oncology Research Association CCOP	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Saint Joseph Mercy Port Huron	Port Huron	Michigan
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Geisinger Medical Oncology-Pottsville	Pottsville	Pennsylvania
United States	Cancer Center of Kansas - Pratt	Pratt	Kansas
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Kaiser Permanente-Redwood City	Redwood City	California
United States	Beebe Health Campus	Rehoboth Beach	Delaware
United States	New York Oncology Hematology PC - Rexford	Rexford	New York
United States	Kaiser Permanente-Richmond	Richmond	California
United States	Reid Hospital and Health Care Services	Richmond	Indiana
United States	Kaiser Permanente Medical Center	Riverside	California
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	University of Rochester	Rochester	New York
United States	SwedishAmerican Regional Cancer Center/ACT	Rockford	Illinois
United States	Phelps County Regional Medical Center	Rolla	Missouri
United States	Saint John's Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Kaiser Permanente-Roseville	Roseville	California
United States	Kaiser Permanente - Sacramento	Sacramento	California
United States	Kaiser Permanente-South Sacramento	Sacramento	California
United States	Saint Mary's of Michigan	Saginaw	Michigan
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Saint John's Mercy Medical Center	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Metro-Minnesota CCOP	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	Kaiser Permanente	San Diego	California
United States	Kaiser Permanente at San Diego	San Diego	California
United States	California Pacific Medical Center	San Francisco	California
United States	Kaiser Permanente-San Francisco	San Francisco	California
United States	UCSF-Mount Zion	San Francisco	California
United States	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California
United States	Kaiser Permanente Health Care	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	Nanticoke Memorial Hospital	Seaford	Delaware
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Mercy Medical Center-Sioux City	Sioux City	Iowa
United States	Saint Luke's Regional Medical Center	Sioux City	Iowa
United States	Siouxland Hematology Oncology Associates	Sioux City	Iowa
United States	Hematology Oncology Associates of Illinois - Skokie	Skokie	Illinois
United States	Kaiser Permanente-South San Francisco	South San Francisco	California
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Ozark Health Ventures LLC dba Cancer Research for The Ozarks Springfield	Springfield	Missouri
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Stanford University Hospitals and Clinics	Stanford	California
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	Cleveland Clinic Cancer Center-Strongsville	Strongsville	Ohio
United States	Flower Hospital	Sylvania	Ohio
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	Mercy Saint Anne Hospital	Toledo	Ohio
United States	Saint Vincent Mercy Medical Center	Toledo	Ohio
United States	The Toledo Hospital/Toledo Children's Hospital	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	New York Oncology Hematology PC - Troy	Troy	New York
United States	Upper Valley Medical Center	Troy	Ohio
United States	Tulsa Cancer Institute	Tulsa	Oklahoma
United States	Kaiser Permanente Medical Center-Vacaville	Vacaville	California
United States	Kaiser Permanente-Vallejo	Vallejo	California
United States	Sutter Solano Medical Center	Vallejo	California
United States	Virtua West Jersey Hospital Voorhees	Voorhees	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Kaiser Permanente-Walnut Creek	Walnut Creek	California
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Fulton County Health Center	Wauseon	Ohio
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
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	Associates In Womens Health	Wichita	Kansas
United States	Cancer Center of Kansas - Main Office	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Via Christi Regional Medical Center	Wichita	Kansas
United States	Wichita CCOP	Wichita	Kansas
United States	Geisinger Wyoming Valley	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	Minnesota Oncology and Hematology PA-Woodbury	Woodbury	Minnesota
United States	Kaiser Permanente	Woodland Hills	California
United States	Greene Memorial Hospital	Xenia	Ohio
United States	Genesis HealthCare System	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
Primary	Progression-free Survival	Progression-free survival (PFS) is defined as the time from randomization to progression or death without evidence of progression. Progression was evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) and defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Kaplan-Meier method was used to estimate PFS.	Assessed every 3 months for 3 years and then every 6 months for years 3-5
Secondary	Proportion of Patients With Response	Response was evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) and defined as either complete response (CR) or partial response (PR).; CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.; PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.	Assessed every 3 months for 3 years and then every 6 months for years 3-5
Secondary	Overall Survival	Overall survival is defined as time from randomization to death or date last known alive.	Assessed every 3 months for 3 years and then every 6 months for years 3-5
Secondary	Association Between Methyl Guanine Methyltransferase (MGMT) Status by Immunohistochemistry (IHC) and Response	Response was evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) and defined as either complete response (CR) or partial response (PR). CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.; MGMT status was determined by IHC using paraffin-embedded sections of 4µm. A score (H-score) was generated based on the findings and scoring was performed by two pathologists. This H-score ranges from 0 (no staining in the tumor) to 300 (diffuse intense staining of the tumor). The highest score was used if there was disagreement. H-scores were grouped into 3 standard categories for MGMT status: Category 1 - <=50 Category 2 - 51-100 Category 3 - >100	Assessed every 3 months for 3 years and then every 6 months for years 3-5
Secondary	Association Between Methyl Guanine Methyltransferase (MGMT) Status by Promoter Methylation and Response	Response was evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) and defined as either complete response (CR) or partial response (PR).; CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.; PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.; MGMT status is determined by promoter methylation, a clinically validated methylation-specific polymerase chain reaction (PCR) analysis. A tumor sample is considered positive for MGMT promoter methylation if an 80bp band is detected in the methylated PCR reaction. It would be considered MGMT negative if an 80bp band is not detected in the methylated PCR reaction.	Assessed every 3 months for 3 years and then every 6 months for years 3-5