A Randomized Phase II Study of Cisplatin and Etoposide in Combination With Either Hedgehog Inhibitor GDC-0449 or IGF-1R MOAB IMC-A12 for Patients With Extensive Stage

Extensive Stage Small Cell Lung Carcinoma Clinical Trial

Official title:

A Randomized Phase II Study of Cisplatin and Etoposide in Combination With Either Hedgehog Inhibitor GDC-0449 or IGF-1R MOAB IMC-A12 for Patients With Extensive Stage Small Cell Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00887159
• Other study ID #: NCI-2011-01917
• Secondary ID: NCI-2011-0191709
• Status: Completed
• Phase: Phase 2
• Start date: July 16, 2009
• Est. completion date: November 15, 2016

Study information

• Verified date: December 2020
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase II trial studies cisplatin and etoposide to see how well they work when given with or without Hedgehog inhibitor GDC-0449 (vismodegib) or IGF-1R MOAB IMC-A12 (cixutumumab) in treating patients with extensive-stage small cell lung cancer. Drugs used in chemotherapy, such as cisplatin, 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. Etoposide may slow the growth of tumor cells by blocking some of the enzymes needed for cell growth. Vismodegib may slow the growth of tumor cells. Monoclonal antibodies, such as cixutumumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving cisplatin and etoposide are more effective when given together with vismodegib or cixutumumab in treating small cell lung cancer.

Description:

PRIMARY OBJECTIVES:

I. To evaluate the progression-free survival (PFS) of patients with extensive stage small cell lung cancer (SCLC-ED) treated with cisplatin and etoposide (CE), CE with hedgehog (HH) inhibitor GDC-0449 (vismodegib), and CE with insulin-like growth factor-1 receptor (IGF-1R) monoclonal antibody (IMC-A12) (cixutumumab).

SECONDARY OBJECTIVES:

I. To evaluate response rate, overall survival, and toxicity for each arm. II. To explore putative correlates of clinical benefit from combination therapy in tumor and circulating tumor cells in patients treated on this protocol.

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM A (CE): Patients receive cisplatin (75 mg/m^2) intravenously (IV) over 1-2 hours on day 1 and etoposide (100 mg/m^2) IV over 1-2 hours on days 1-3. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

ARM B (CE +GDC-0449): Patients receive cisplatin and etoposide as in Arm A and vismodegib (GDC-0449; 150 mg tablet) orally (PO) once daily (QD) on days 1-21. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive vismodegib alone QD in the absence of disease progression or unacceptable toxicity.

ARM C (CE + IMC-A12): Patients receive cisplatin and etoposide as in Arm A and cixutumumab (IMC-A12; 6 mg/kg) IV over 1 hour on days 1, 8, and 15. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive cixutumumab alone once weekly 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 1 year.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 168
• Est. completion date: November 15, 2016
• Est. primary completion date: November 15, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed small cell lung cancer (SCLC)

• Extensive stage SCLC

• Extensive stage disease: the extensive disease classification for this protocol includes all patients with disease sites not defined as limited stage; limited stage disease category includes patients with disease restricted to one hemithorax with regional lymph node metastases, including hilar, ipsilateral and contralateral mediastinal, and/or ipsilateral supraclavicular nodes; extensive disease patients are defined as those patients with extrathoracic metastatic disease, malignant pleural effusion, bilateral or contralateral supraclavicular adenopathy

• Measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST); baseline measurements and evaluations of all sites of disease must be obtained =< 4 weeks prior to randomization

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

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

• Platelets >= 100,000/mm^3

• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase)/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase) =< 3 x institutional ULN (=< 5 x ULN if liver function test [LFT] elevations are due to liver metastases)

• Creatinine =< 1.5 x institutional ULN OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels > 1.5 x institutional ULN

• Leukocytes >= 3,000/mm^3

• Hemoglobin >= 9 g/dL

• Fasting serum glucose < 120 mg/dL or below institutional ULN =< 7 days prior to protocol randomization

• Patients with central nervous system (CNS) metastases will be eligible if they have completed a course of CNS radiotherapy and have stable neurologic function for a minimum of 28 days prior to study randomization; radiotherapy must have been completed a minimum of 28 days prior to randomization, and patients must have recovered from any adverse events related to the radiotherapy (except alopecia and grade 1 neuropathy) and have stable neurologic function for a minimum of 28 days prior to study randomization

• NOTE: the use of prophylactic cranial irradiation (recommended dose 25 Gy) in those who completed protocol chemotherapy and have a response (in the absence of progressive disease [PD]) is allowed; for patients on Arms B and C, GDC-0449 and IMC-A12 will be held while patient is receiving prophylactic cranial irradiation (PCI); these agents can be reinstituted after PCI is completed

• Women of child-bearing potential (WCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation

• WCBP must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse; the two methods of reliable contraception must include one highly effective method (i.e., intrauterine device [IUD], hormonal [birth control pills, injections, or implants], tubal ligation, partner?s vasectomy) and one additional effective (barrier) method (i.e., latex condom, diaphragm, cervical cap); WCBP must be referred to a qualified provider of contraceptive methods if needed

• NOTE: the WCBP randomized to Arm B must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the following two additional time periods related to this study: 1) while participating in the study; and 2) for at least 12 months after discontinuation from the study

• Before starting the study drugs, all WCBP must have a negative pregnancy test (sensitivity of at least 50 mIU/mL); the pregnancy test must be performed within 10-14 days prior to randomization

• NOTE: the WCBP randomized to Arm B must have a second pregnancy test performed within the 24 hours prior to the start of the GDC-0449; the subject may not receive GDC-0449 until the investigator has verified that the results of these pregnancy tests are negative

• The WCBP randomized to Arm B will be warned that sharing the study drug is prohibited and will be counseled about pregnancy precautions and potential risks or fetal exposure; she must also agree to abstain from donating blood during study participation and at least 12 months after discontinuation from the study drug

• NOTE: male subjects randomized to Arm B must agree to use a latex condom during sexual contact with WCBP while participating in the study and for at least 12 months following discontinuation from the study even if he has undergone a successful vasectomy

• Male subjects randomized to Arm B will be warned that sharing study drug is prohibited and will be counseled about pregnancy precautions and potential risks of fetal exposure; male subjects must agree to abstain from donating blood, semen, or sperm during study participation and for at least 3 months after discontinuation from the study drug

Exclusion Criteria:

• Pregnant or breastfeeding; all WCBP must have a blood test within 10-14 days prior to randomization to rule out pregnancy

• Prior chemotherapy or biologic therapy for SCLC; patients with prior radiation may be eligible or after palliative radiotherapy for other sites of disease; patients receiving prior radiation cannot start therapy within 14 days after completion of radiation, and must have recovered from adverse events attributed to radiation; no previous irradiation to the only site of measurable or evaluable disease, unless that site had subsequent evidence of progression

• Receiving any other investigational agents

• History of allergic reactions attributed to compounds of similar chemical or biological composition to GDC-0449 and IMC-A12 or other agents used in the study

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy

• Poorly controlled diabetes mellitus; patients with a history of diabetes mellitus are allowed to participate, provided that their blood glucose is within normal range (fasting < 120 mg/dL or below institutional upper limit of normal) and that they are on a stable dietary or therapeutic regimen for this condition

• Patients with major surgery, hormonal therapy (other than replacement), within 4 weeks prior to entering the study or those who have not recovered from adverse events

• Prior treatment with other agents targeting the IGFR or the Hedgehog signaling pathway

Related Conditions & MeSH terms

• Carcinoma
• Extensive Stage Small Cell Lung Carcinoma
• Lung Neoplasms
• Recurrent Small Cell Lung Carcinoma
• Small Cell Lung Carcinoma

Intervention

Drug:
• Cisplatin
Given IV

Biological:
• Cixutumumab
Given IV

Drug:
• Etoposide
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Vismodegib
Given PO

Locations

Country	Name	City	State
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	Bixby Medical Center	Adrian	Michigan
United States	Hickman Cancer Center	Adrian	Michigan
United States	Summa Akron City Hospital/Cooper Cancer 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	Lovelace Medical Center-Saint Joseph Square	Albuquerque	New Mexico
United States	Presbyterian Kaseman Hospital	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
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	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	The Medical Center of Aurora	Aurora	Colorado
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	Summa Barberton Hospital	Barberton	Ohio
United States	Mary Rutan Hospital	Bellefontaine	Ohio
United States	Sanford Clinic North-Bemidgi	Bemidji	Minnesota
United States	Constantinou, Costas L MD (UIA Investigator)	Bettendorf	Iowa
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Boca Raton Regional Hospital	Boca Raton	Florida
United States	Tufts Medical Center	Boston	Massachusetts
United States	Boulder Community Hospital	Boulder	Colorado
United States	Toledo Clinic Cancer Centers-Bowling Green	Bowling Green	Ohio
United States	Wellmont Medical Associates Oncology and Hematology-Bristol	Bristol	Tennessee
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Montefiore Medical Center-Weiler Hospital	Bronx	New York
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Butler Memorial Hospital	Butler	Pennsylvania
United States	Aultman Health Foundation	Canton	Ohio
United States	Graham Hospital Association	Canton	Illinois
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Mercy Medical Center	Canton	Ohio
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	West Virginia University Charleston	Charleston	West Virginia
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	Hematology and Oncology Associates	Chicago	Illinois
United States	John H Stroger Jr Hospital of Cook County	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	Presence Saint Joseph Hospital-Chicago	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin
United States	Case Western Reserve University	Cleveland	Ohio
United States	New York Oncology Hematology PC - Clifton Park	Clifton Park	New York
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	North Coast Cancer Care-Clyde	Clyde	Ohio
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Columbus NCI Community Oncology Research Program	Columbus	Ohio
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Dallas VA Medical Center	Dallas	Texas
United States	Parkland Memorial Hospital	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Beaumont Hospital-Dearborn	Dearborn	Michigan
United States	Atlanta VA Medical Center	Decatur	Georgia
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Heartland Cancer Research NCORP	Decatur	Illinois
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Colorado Cancer Research Program NCORP	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	SCL Health Saint Joseph Hospital	Denver	Colorado
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa
United States	Mercy Capitol	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	Essentia Health Cancer Center	Duluth	Minnesota
United States	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota
United States	Miller-Dwan Hospital	Duluth	Minnesota
United States	Veterans Adminstration New Jersey Health Care System	East Orange	New Jersey
United States	The Memorial Hospital at Easton	Easton	Maryland
United States	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin
United States	Fairview-Southdale Hospital	Edina	Minnesota
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Elmhurst Memorial Hospital	Elmhurst	Illinois
United States	Hematology Oncology Center Incorporated	Elyria	Ohio
United States	Mercy Cancer Center-Elyria	Elyria	Ohio
United States	Swedish Medical Center	Englewood	Colorado
United States	Ephrata Cancer Center	Ephrata	Pennsylvania
United States	Eureka Hospital	Eureka	Illinois
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Clinic North-Fargo	Fargo	North Dakota
United States	Lake Region Healthcare Corporation-Cancer Care	Fergus Falls	Minnesota
United States	Hunterdon Medical Center	Flemington	New Jersey
United States	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Vanderbilt-Ingram Cancer Center Cool Springs	Franklin	Tennessee
United States	Frederick Memorial Hospital	Frederick	Maryland
United States	Fredericksburg Oncology Inc	Fredericksburg	Virginia
United States	Unity Hospital	Fridley	Minnesota
United States	Galesburg Cottage Hospital	Galesburg	Illinois
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Adams Cancer Center	Gettysburg	Pennsylvania
United States	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado
United States	North Colorado Medical Center	Greeley	Colorado
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Cherry Tree Cancer Center	Hanover	Pennsylvania
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Illinois CancerCare-Havana	Havana	Illinois
United States	Mason District Hospital	Havana	Illinois
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	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	Allegiance Health	Jackson	Michigan
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Joliet Oncology-Hematology Associates Limited	Joliet	Illinois
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	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Cancer Center of Kansas-Kingman	Kingman	Kansas
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Lancaster General Hospital	Lancaster	Pennsylvania
United States	Saint Mary Medical and Regional Cancer Center	Langhorne	Pennsylvania
United States	Sparrow Hospital	Lansing	Michigan
United States	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Lewistown Hospital	Lewistown	Pennsylvania
United States	Cancer Center of Kansas-Liberal	Liberal	Kansas
United States	Southwest Medical Center	Liberal	Kansas
United States	NorthShore Hematology Oncology-Libertyville	Libertyville	Illinois
United States	Lima Memorial Hospital	Lima	Ohio
United States	Saint Rita's Medical Center	Lima	Ohio
United States	Nebraska Cancer Research Center	Lincoln	Nebraska
United States	Saint Mary Mercy Hospital	Livonia	Michigan
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Longmont United Hospital	Longmont	Colorado
United States	Doctors Carrol, Sheth, Raghavan	Louisville	Kentucky
United States	McKee Medical Center	Loveland	Colorado
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Mcdonough District Hospital	Macomb	Illinois
United States	Medical Center of Central Georgia	Macon	Georgia
United States	Dean Hematology and Oncology Clinic	Madison	Wisconsin
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	Mercy Medical Center - North Iowa	Mason City	Iowa
United States	Saint Luke's Hospital	Maumee	Ohio
United States	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio
United States	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Columbia Saint Mary's Water Tower Medical Commons	Milwaukee	Wisconsin
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Garneau, Stewart C MD (UIA Investigator)	Moline	Illinois
United States	Porubcin, Michael MD (UIA Investigator)	Moline	Illinois
United States	Sharis, Christine M MD (UIA Investigator)	Moline	Illinois
United States	Spector, David MD (UIA Investigator)	Moline	Illinois
United States	Stoffel, Thomas J MD (UIA Investigator)	Moline	Illinois
United States	Trinity Medical Center	Moline	Illinois
United States	Holy Family Medical Center	Monmouth	Illinois
United States	Illinois CancerCare-Monmouth	Monmouth	Illinois
United States	Mercy Memorial Hospital	Monroe	Michigan
United States	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York
United States	Licking Memorial Hospital	Newark	Ohio
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	Illinois Cancer Specialists-Niles	Niles	Illinois
United States	Bromenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center Foundation	Normal	Illinois
United States	Illinois CancerCare-Community Cancer Center	Normal	Illinois
United States	Fisher-Titus Medical Center	Norwalk	Ohio
United States	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Immanuel Medical Center	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Saint Charles Hospital	Oregon	Ohio
United States	Toledo Clinic Cancer Centers-Oregon	Oregon	Ohio
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois
United States	Ottumwa Regional Health Center	Ottumwa	Iowa
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois
United States	Pekin Hospital	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Illinois Valley Hospital	Peru	Illinois
United States	Einstein Medical Center Philadelphia	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Lake Huron Medical Center	Port Huron	Michigan
United States	Cancer Center of Kansas - Pratt	Pratt	Kansas
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	New York Oncology Hematology PC - Rexford	Rexford	New York
United States	Ascension Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Marshfield Clinic-Rice Lake Center	Rice Lake	Wisconsin
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Swedish American Hospital	Rockford	Illinois
United States	SwedishAmerican Regional Cancer Center/ACT	Rockford	Illinois
United States	Saint Mary's of Michigan	Saginaw	Michigan
United States	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	North Coast Cancer Care	Sandusky	Ohio
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	Hematology and Oncology Associates of North East Pennsylvania	Scranton	Pennsylvania
United States	Mercy Hospital	Scranton	Pennsylvania
United States	Scranton Hematology Oncology	Scranton	Pennsylvania
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 Regional Cancer Center	Sioux City	Iowa
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Avera McKennan Hospital and University Health Center	Sioux Falls	South Dakota
United States	Medical X-Ray Center	Sioux Falls	South Dakota
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	Hematology Oncology Associates of Illinois - Skokie	Skokie	Illinois
United States	Sparta Cancer Treatment Center	Sparta	New Jersey
United States	Illinois CancerCare-Spring Valley	Spring Valley	Illinois
United States	Saint Margaret's Hospital	Spring Valley	Illinois
United States	Memorial Medical Center	Springfield	Illinois
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Geisinger Medical Group	State College	Pennsylvania
United States	Mount Nittany Medical Center	State College	Pennsylvania
United States	Ascension Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Flower Hospital	Sylvania	Ohio
United States	North Suburban Medical Center	Thornton	Colorado
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	Smilow Cancer Hospital-Torrington Care Center	Torrington	Connecticut
United States	New York Oncology Hematology PC - Troy	Troy	New York
United States	Natalie Warren Bryant Cancer Center at Saint Francis	Tulsa	Oklahoma
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	Fulton County Health Center	Wauseon	Ohio
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Reading Hospital	West Reading	Pennsylvania
United States	Saint Ann's Hospital	Westerville	Ohio
United States	Marshfield Clinic - Weston Center	Weston	Wisconsin
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	Wheeling Hospital/Schiffler Cancer Center	Wheeling	West Virginia
United States	Dickstein Cancer Treatment Center	White Plains	New York
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	Via Christi Regional Medical Center	Wichita	Kansas
United States	Wichita NCI Community Oncology Research Program	Wichita	Kansas
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	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	Lankenau Medical Center	Wynnewood	Pennsylvania
United States	WellSpan Health-York Hospital	York	Pennsylvania
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS)	Progression-free survival (PFS) is defined as the time from randomization to death or disease progression, whichever occurred first. Patients who were alive at the time of analysis are censored at the date at which they are last known to be alive and progression-free.	Assessed every 6 weeks while on treatment or observation; follow-up after discontinuation of treatment or observation: every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-3 years from study entry
Secondary	Response Rate	Response rate is defined as number of patients with complete response (CR) or partial response (PR) divided by all eligible and treated patients. Responses are evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) guideline. CR is defined as disappearance of all target and non-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), and persistence of one or more non-target lesion(s).	Assessed every 6 weeks while on treatment or observation; follow-up after discontinuation of treatment or observation: every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-3 years from study entry
Secondary	Overall Survival (OS)	Overall survival is defined as the time from randomization to death or date of last known alive.	Assessed every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-3 years from study entry
Secondary	PFS	Progression-free survival (PFS) is defined as the time from randomization to death or disease progression, whichever occurred first. Patients who were alive at the time of analysis are censored at the date at which they are last known to be alive and progression-free. This analysis is to evaluate the association between PFS and circulating tumor cells (CTCs).	Assessed every 6 weeks while on treatment or observation; follow-up after discontinuation of treatment or observation: every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-3 years from study entry

External Links

•   Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.