Carboplatin and Paclitaxel Combined With Cetuximab and/or IMC-A12 in Patients With Advanced Non-Small Cell Lung Cancer

Stage IV Non-small Cell Lung Cancer Clinical Trial

Official title:

Three-Arm Randomized Phase II Study of Carboplatin and Paclitaxel in Combination With Cetuximab, IMC-A12 or Both in Patients With Advanced Non-Small Cell Lung Cancer Who Will Not Receive Bevacizumab-Based Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00986674
• Other study ID #: NCI-2011-01976
• Secondary ID: E4508U10CA021115
• Status: Completed
• Phase: Phase 2
• First received: September 29, 2009
• Last updated: September 19, 2014
• Start date: September 2009
• Est. completion date: December 2013

Study information

• Verified date: March 2014
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This randomized phase II trial is studying how well giving carboplatin and paclitaxel together with cetuximab and/or cixutumumab (IMC-A12) works in treating patients with stage IIIB or stage IV non-small cell lung cancer. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab and cixutumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving chemotherapy together with monoclonal antibody therapy may kill more tumor cells. It is not yet known whether carboplatin and paclitaxel are more effective when given with cetuximab and/or cixutumumab in treating non-small cell lung cancer.

Description:

PRIMARY OBJECTIVES:

I. To evaluate the progression-free survival of patients with non-small cell lung cancer (NSCLC) randomized to carboplatin plus paclitaxel plus cetuximab or carboplatin plus paclitaxel plus cixutumumab (IMC-A12) or carboplatin plus paclitaxel plus cetuximab plus cixutumumab.

SECONDARY OBJECTIVES:

I. To evaluate the response rate, disease control rate (complete response plus partial response plus stable disease), and toxicities for each arm.

II. To evaluate epidermal growth factor receptor (EGFR) by Immunohistochemistry (IHC), mutation, and gene copy number, Insulin-like growth factor 1 receptor (IGF-1R) and Insulin-like growth factor 2 receptor (IGF-2R) expression (both phosphorylated and unphosphorylated states), expression of p-AKT (ie, Protein Kinase B) by IHC, and k-ras mutation.

III. Plasma-based biomarkers will be evaluated for total and free insulin-like growth factor 1 and 2, IGF-growth factor binding protein 3 (IGFBP3) and circulating levels of epidermal growth factor (EGF) and Transforming growth factor (TGF) alpha.

IV. To evaluate overall survival on each of the three arms.

OUTLINE: This is a multicenter study. Patients are stratified according to gender and histology (squamous cell vs non-squamous cell). Patients are randomized to 1 of 3 treatment arms.

ARM I: Patients receive carboplatin intravenously (IV) over 15-30 minutes and paclitaxel IV over 3 hours on days 1 and 22 and cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and

36. Treatment repeats every 42 days for 2 courses. Patients with stable or responding disease after 2 courses proceed to maintenance therapy with cetuximab alone on days 1, 8, 15, 22, 29, and 36. Treatment with cetuximab repeats every 42 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive carboplatin and paclitaxel as in arm I. Patients also receive cixutumumab IV over 1 hour on days 1, 15, and 29. Treatment repeats every 42 days for 2 courses. Patients with stable or responding disease after 2 courses proceed to maintenance therapy with cixutumumab alone on days 1, 15, and 29. Treatment with cixutumumab repeats every 42 days in the absence of disease progression or unacceptable toxicity.

ARM III: Patients receive carboplatin, paclitaxel, and cetuximab as in arm I. Patients also receive cixutumumab as in arm II. Treatment repeats every 42 days for 2 courses. Patients with stable or responding disease after 2 courses proceed to maintenance therapy with cetuximab as in arm I and cixutumumab as in arm II.

Tumor tissue samples are collected at baseline for analysis of EGFR expression by IHC, mutation, and gene copy number; IGF-1R and IGF-2R expression (both phosphorylated and unphosphorylated states); p-AKT expression by IHC; and k-ras mutation. Blood, serum, and plasma samples are collected periodically for biomarker analysis.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 1 year.

PROJECTED ACCRUAL: 200 patients

Recruitment information / eligibility

• Status: Completed
• Enrollment: 140
• Est. completion date: December 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)

• Stage IIIB disease

• T4, NX with nodule in ipsilateral lung lobe allowed provided patient is not a candidate for combined chemotherapy and radiotherapy

• Stage IV disease (includes M1a and M1b)

• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria

• Ineligible for or refused treatment with bevacizumab

• No untreated or symptomatic central nervous system (CNS) metastases

• Patients with a history of CNS metastases that are definitively treated, stable, and controlled are eligible provided the following criteria are met:

• Definitive therapy (surgery and/or radiotherapy) has been administered

• Not planning to undergo additional treatment for brain metastases

• Clinically stable

• Off corticosteroids or on a stable dose of corticosteroids for = 14 days before study entry

• ECOG performance status 0-1

• Leukocytes > 3,000/mm^3

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

• Hemoglobin > 9 g/dL

• Platelet count > 100,000/mm^3

• Total bilirubin = 1.5 times upper limit of normal (ULN)

• Aspartate Aminotransferase (AST) < 3 times ULN (< 5 times ULN if elevations due to liver metastases)

• Creatinine < 1.5 times ULN OR creatinine clearance > 60 mL/min

• Fasting serum glucose < 120 mg/dL

• Partial thromboplastin time (PTT) = 1.2 times ULN and international normalized ratio (INR) = 1.5 (unless patient is on anticoagulation therapy)

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 3 months after the last dose of cixutumumab

• No poorly controlled diabetes mellitus

• Patients with a history of diabetes mellitus are eligible provided their blood glucose is within normal range and they are on a stable dietary or therapeutic regimen for this condition

• No other prior or concurrent malignancy, except for the following:

• Curatively treated malignancy with no known active disease for = 3 years AND is considered to be at low risk for recurrence by the treating physician

• Adequately treated nonmelanoma skin cancer or lentigo maligna with no evidence of disease

• Adequately treated cervical carcinoma in situ with no evidence of disease

• Prostatic intraepithelial neoplasia with no evidence of prostate cancer

• Concurrent therapeutic anticoagulation allowed provided there is no bleeding and patient is on a stable dose of anticoagulation therapy (e.g., Warfarin with an INR of 2-3) for > 2 weeks prior to study entry

• At least 21 days since prior radiotherapy

• More than 4 weeks since prior major surgery or hormonal therapy (other than hormone replacement therapy) and recovered

• More than 1 year since prior neoadjuvant or adjuvant chemotherapy

Exclusion criteria:

• Small cell lung cancer or mixed small cell and NSCLC

• History of allergic reactions attributed to compounds of similar chemical or biological composition to cixutumumab

• History of any medical or psychiatric condition, addictive disorder, or laboratory abnormality that, in the opinion of the investigator, may increase the risks associated with study participation or study treatments or may interfere with the conduct of the study or interpretation of study results

• Prior agents targeting the EGFR or Insulin-like growth factor (IGFR) pathways

• Prior therapy for advanced NSCLC, except for surgery and/or radiotherapy

• Prior systemic therapy, including bevacizumab for advanced stage NSCLC

• Pregnant or nursing

• Peripheral neuropathy > grade 1 as per Common Terminology Criteria for Adverse Event (CTCAE) v 4.0

• History of or suspected interstitial pneumonitis or pulmonary fibrosis on imaging

• Significant uncontrolled cardiac disease within the past 6 months, including any of the following:

• Uncontrolled hypertension (BP > 150/100 mm Hg)

• Unstable angina

• Recent myocardial infarction

• Uncontrolled congestive heart failure

• Cardiomyopathy with decreased ejection fraction

• Arterial thrombosis, pulmonary embolus, deep vein thrombosis, or hemorrhagic disorders within the past 28 days

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Recurrent Non-small Cell Lung Cancer
• Stage IIIB Non-small Cell Lung Cancer
• Stage IV Non-small Cell Lung Cancer

Intervention

Biological:
• cixutumumab
Given IV

Drug:
• carboplatin
Given IV
• paclitaxel
Given IV

Biological:
• cetuximab
Given IV

Locations

Country	Name	City	State
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	New York Oncology Hematology PC - Amsterdam	Amsterdam	New York
United States	Michigan Cancer Research Consortium Community Clinical Oncology Program	Ann Arbor	Michigan
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Fox Valley Hematology and Oncology	Appleton	Wisconsin
United States	The Medical Center of Aurora	Aurora	Colorado
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Mary Rutan Hospital	Bellefontaine	Ohio
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	Boulder Community Hospital	Boulder	Colorado
United States	Toledo Clinic Cancer Centers-Bowling Green	Bowling Green	Ohio
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Graham Hospital Association	Canton	Illinois
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Cedar Rapids Oncology Association	Cedar Rapids	Iowa
United States	Mercy Hospital	Cedar Rapids	Iowa
United States	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	West Virginia University Charleston	Charleston	West Virginia
United States	University of Virginia	Charlottesville	Virginia
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	North Coast Cancer Care-Clyde	Clyde	Ohio
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Columbus CCOP	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	Danbury Hospital	Danbury	Connecticut
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Oakwood Hospital	Dearborn	Michigan
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Colorado Cancer Research Program CCOP	Denver	Colorado
United States	Exempla Saint Joseph Hospital	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	Saint John Hospital and Medical Center	Detroit	Michigan
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	Essentia Health Duluth Clinic CCOP	Duluth	Minnesota
United States	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota
United States	Miller-Dwan Hospital	Duluth	Minnesota
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	Elkhart General Hospital	Elkhart	Indiana
United States	Hematology Oncology Center Incorporated	Elyria	Ohio
United States	Swedish Medical Center	Englewood	Colorado
United States	Green Bay Oncology - Escanaba	Escanaba	Michigan
United States	Eureka Hospital	Eureka	Illinois
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Evanston CCOP-NorthShore University HealthSystem	Evanston	Illinois
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	Fredericksburg Oncology Inc	Fredericksburg	Virginia
United States	Unity Hospital	Fridley	Minnesota
United States	Illinois CancerCare Galesburg	Galesburg	Illinois
United States	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado
United States	North Colorado Medical Center	Greeley	Colorado
United States	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin
United States	Saint Mary's Hospital	Green Bay	Wisconsin
United States	Saint Vincent Hospital	Green Bay	Wisconsin
United States	Saint Francis Hospital and Medical Center	Hartford	Connecticut
United States	Illinois CancerCare-Havana	Havana	Illinois
United States	Mason District Hospital	Havana	Illinois
United States	Geisinger Medical Center-Cancer Center Hazelton	Hazleton	Pennsylvania
United States	Hinsdale Hematology Oncology Associates Incorporated	Hinsdale	Illinois
United States	New York Oncology Hematology PC-Hudson	Hudson	New York
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Indiana University Medical Center	Indianapolis	Indiana
United States	Richard L. Roudebush Veterans Affairs Medical Center	Indianapolis	Indiana
United States	Wishard Hospital	Indianapolis	Indiana
United States	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan
United States	Allegiance Health	Jackson	Michigan
United States	UW Cancer Center Johnson Creek	Johnson Creek	Wisconsin
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Cancer Center of Kansas-Kingman	Kingman	Kansas
United States	Community Howard Regional Health	Kokomo	Indiana
United States	Gundersen Lutheran	La Crosse	Wisconsin
United States	Indiana University Health La Porte Hospital	La Porte	Indiana
United States	IU Health Arnett	Lafayette	Indiana
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Lancaster General Hospital	Lancaster	Pennsylvania
United States	Sparrow Hospital	Lansing	Michigan
United States	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	New York Oncology Hematology PC - Latham	Latham	New York
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Cancer Center of Kansas-Liberal	Liberal	Kansas
United States	Lima Memorial Hospital	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	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	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	UW Health Oncology - 1 South Park	Madison	Wisconsin
United States	Manchester Memorial Hospital	Manchester	Connecticut
United States	Holy Family Memorial Hospital	Manitowoc	Wisconsin
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	Bay Area Medical Center	Marinette	Wisconsin
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	Saint Luke's Hospital	Maumee	Ohio
United States	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio
United States	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana
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	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	Knox Community Hospital	Mount Vernon	Ohio
United States	Nashville Oncology Associates PC	Nashville	Tennessee
United States	Licking Memorial Hospital	Newark	Ohio
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Cancer Center of Kansas - Newton	Newton	Kansas
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	Green Bay Oncology - Oconto Falls	Oconto Falls	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 CCOP	Omaha	Nebraska
United States	UHHS-Chagrin Highlands Medical Center	Orange Village	Ohio
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	Paoli Memorial Hospital	Paoli	Pennsylvania
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	Pekin Hospital	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	Illinois Valley Hospital	Peru	Illinois
United States	Abramson Cancer Center of The University of Pennsylvania	Philadelphia	Pennsylvania
United States	Albert Einstein Medical Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Saint Joseph Mercy Port Huron	Port Huron	Michigan
United States	Pottstown Memorial Medical Center	Pottstown	Pennsylvania
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	Marshfield Clinic at James Beck Cancer Center	Rhinelander	Wisconsin
United States	Marshfield Clinic-Rice Lake Center	Rice Lake	Wisconsin
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Saint Mary's of Michigan	Saginaw	Michigan
United States	Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Metro-Minnesota CCOP	Saint Louis Park	Minnesota
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	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	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 Hematology Oncology Associates	Sioux City	Iowa
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Northern Indiana Cancer Research Consortium	South Bend	Indiana
United States	Illinois CancerCare-Spring Valley	Spring Valley	Illinois
United States	Saint Margaret's Hospital	Spring Valley	Illinois
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Lakeland Hospital	St. Joseph	Michigan
United States	Stanford University Hospitals and Clinics	Stanford	California
United States	Geisinger Medical Group	State College	Pennsylvania
United States	Marshfield Clinic Cancer Care at Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Flower Hospital	Sylvania	Ohio
United States	Scott and White Memorial Hospital	Temple	Texas
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	New York Oncology Hematology PC - Troy	Troy	New York
United States	Natalie Warren Bryant Cancer Center at Saint Francis	Tulsa	Oklahoma
United States	Virtua West Jersey Hospital Voorhees	Voorhees	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Marshfield Clinic-Wausau Center	Wausau	Wisconsin
United States	Fulton County Health Center	Wauseon	Ohio
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Saint Ann's Hospital	Westerville	Ohio
United States	UHHS-Westlake Medical Center	Westlake	Ohio
United States	Marshfield Clinic - Weston Center	Weston	Wisconsin
United States	Exempla Lutheran Medical Center	Wheat Ridge	Colorado
United States	Wheeling Hospital	Wheeling	West Virginia
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	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Riverview Hospital	Wisconsin Rapids	Wisconsin
United States	Minnesota Oncology and Hematology PA-Woodbury	Woodbury	Minnesota
United States	Lankenau Hospital	Wynnewood	Pennsylvania
United States	Mainline Health CCOP	Wynnewood	Pennsylvania
United States	Genesis HealthCare System	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	Progression free survival is defined as time from registration to disease progression or death from any cause, whichever occurred earlier. Disease progression was assessed via Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, and defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, and/or the appearance of one or more new lesion(s), and/or unequivocal progression of existing nontarget lesions .; All eligible and treated patients were included in the analysis.	Tumor measurements are repeated every 6 weeks while on treatment. After off treatment, assessed every 3 months if patient is < 2 years from study entry and every 6 months in year 3	No
Secondary	Overall Survival	Overall survival is defined as time from registration to death from any cause.	assessed every 3 months if patient is < 2 years from study entry and every 6 months in year 3	No
Secondary	Response Rate	Tumor response was assessed via Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Complete response (CR) was defined disappearance of all tumor lesions. Partial response (PR) was defined as as at least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum longest diameter. Overall response rate= CR+PR.	Tumor measurements are repeated every 6 weeks while on treatment. After off treatment, assessed every 3 months if patient is < 2 years from study entry and every 6 months in year 3	No