Paclitaxel and Cisplatin or Topotecan With or Without Bevacizumab in Treating Patients With Stage IVB, Recurrent, or Persistent Cervical Cancer

Cervical Adenocarcinoma Clinical Trial

Official title:

A Randomized Phase III Trial of Cisplatin Plus Paclitaxel With and Without NCI-Supplied Bevacizumab (NSC #704865) Versus the Non-platinum Doublet, Topotecan Plus Paclitaxel, With and Without NCI-Supplied Bevacizumab, in Stage IVB, Recurrent or Persistent Carcinoma of the Cervix

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00803062
• Other study ID #: NCI-2009-01084
• Secondary ID: NCI-2009-01084CD
• Status: Completed
• Phase: Phase 3
• Start date: April 2009
• Est. completion date: February 2013

Study information

• Verified date: July 2019
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase III trial studies the side effects of paclitaxel when given together with cisplatin or topotecan with or without bevacizumab and to compare how well they work in treating patients with stage IVB, cervical cancer that has come back or is persistent. Drugs used in chemotherapy, such as paclitaxel, cisplatin, and topotecan, 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. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether paclitaxel is more effective when given together with cisplatin or topotecan with or without bevacizumab in treating patients with cervical cancer.

Description:

PRIMARY OBJECTIVES:

I. To determine whether the addition of bevacizumab to chemotherapy improves overall survival. Also to determine if a regimen involving paclitaxel and topotecan improves overall survival in comparison to a regimen involving cisplatin and paclitaxel. These regimens are to be evaluated in patients with stage IVB, recurrent, or persistent carcinoma of the cervix.

II. To determine and compare the frequency and severity of adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 for the regimens administered on this study.

SECONDARY OBJECTIVES:

I. To estimate and compare the progression-free survival of patients treated by the regimens investigated on this study.

II. To estimate and compare the proportion of patients with tumor responses by the regimens investigated on this study.

TERTIARY OBJECTIVES:

I. To determine whether the addition of bevacizumab to chemotherapy, or the substitution of cisplatin with topotecan improve the health related quality of life (QOL) as measured by the Functional Assessment of Cancer Therapy-Cervix Trial Outcome Index scale (FACT-Cx TOI) and produce favorable toxicity profiles (with a particular focus on peripheral neuropathy as measured by the Functional Assessment of Cancer Therapy-Gynecologic Oncology Group-Neurotoxicity version 4 [FACT/GOG-Ntx4] subscale and pain as measured by Brief Pain Inventory [BPI] single item).

II. To evaluate the impact of age, race, performance status, stage, histology, grade, disease site, prior chemotherapy with primary radiation, and time to recurrence on response rate, progression-free survival and overall survival of patients with metastatic/recurrent/persistent carcinoma of the cervix.

III. To determine the prevalence of active smoking in this cohort of recurrent cervical cancer patients.

IV. To estimate the extent of tobacco/nicotine dependence in the cohort. V. To determine if smoking is an independent risk factor for progression-free survival and overall survival in this population.

VI. To isolate, enumerate and characterize circulating tumor cells (CTC) recovered from blood drawn pre-cycle 1, pre-cycle 2 and pre-cycle 3 using the CTC-chip developed by the Massachusetts General Hospital (MGH) BioMEMS Resource Center and the MGH Cancer Center.

VII. To determine the association between CTC counts or characteristics and measures of clinical outcome.

VIII. To examine the association between angiogenesis markers in plasma (recovered from blood drawn pre-cycle 1, pre-cycle 2 and pre-cycle 3) and measures of clinical outcome.

IX. To evaluate the association between tumor markers of angiogenesis and hypoxia (using archival formalin-fixed and paraffin-embedded tumor tissue) and measures of clinical outcome.

X. To evaluate the association between single nucleotide polymorphisms (using deoxyribonucleic acid [DNA] extracted from whole blood) and measures of clinical outcome as well as measures of quality of life such as chemotherapy toxicity.

XI. To examine the relationship(s) among the various biomarkers. XII. To develop an optimal prognostic model for progression-free survival and overall survival using clinical covariates, smoking status and the various biomarkers.

OUTLINE: Patients are randomized to 1 of 4 treatment arms.

ARM I: Patients receive paclitaxel intravenously (IV) over 3 hours or 24 hours on day 1 and cisplatin IV on day 1 or 2.

ARM II: Patients receive paclitaxel IV over 3 hours or 24 hours on day 1 and cisplatin IV and bevacizumab IV over 30-90 minutes on day 1 or 2.

ARM III: Patients receive paclitaxel IV over 3 hours on day 1 and topotecan hydrochloride IV over 30 minutes on days 1-3.

ARM IV: Patients receive paclitaxel IV over 3 hours and bevacizumab IV over 30-90 minutes on day 1 and topotecan hydrochloride IV over 30 minutes on days 1-3.

In all arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 452
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have primary stage IVB, recurrent or persistent squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix which is not amenable to curative treatment with surgery and/or radiation therapy

• All patients must have measurable disease; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded); each lesion must be >= 20 mm when measured by conventional techniques, including palpation, plain x-ray, computed tomography (CT), and magnetic resonance imaging (MRI), or >= 10 mm when measured by spiral CT; biopsy confirmation is required if the lesion(s) measures < 30 mm or if the treating physician determines it is clinically indicated; patients must have at least one "target lesion" to be used to assess response on this protocol as defined by Response Evaluation Criteria in Solid Tumors (RECIST); this lesion should be the one that was biopsied if one was performed; tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy

• Absolute neutrophil count (ANC) >= 1500/mcl

• Platelets >= 100,000/mcl

• Serum creatinine =< upper limit of normal (ULN) (Common Toxicity Criteria [CTC] grade 0) or calculated creatinine clearance (Jeliffe formula) >= 60 ml/min

• Bilirubin =< 1.5 x institutional normal

• Serum glutamic oxaloacetic transaminase (SGOT) =< 2.5 x institutional normal

• Alkaline phosphatase =< 2.5 x institutional normal

• Prothrombin time (PT) such that international normalized ratio (INR) is =< 1.5 (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin for management of venous thrombosis including pulmonary thrombo-embolus)

• Partial thromboplastin time (PTT) < 1.2 times the upper limit of normal

• Urine protein-creatinine ratio (UPC ratio) < 1.0

• Patients must have a GOG performance status of 0 or 1

• Patients must have recovered from the effects of surgery, radiation therapy, or chemoradiotherapy; at least six weeks must have elapsed from the last administration of chemoradiotherapy, and at least three weeks must have elapsed from the last administration of radiation therapy alone; at least six weeks must have elapsed from the time of any major surgical procedure prior to randomization

• Patients must have signed an approved informed consent and authorization permitting release of personal health information

• Patients must meet all of the pre-entry requirements, including baseline QOL questionnaire

• Patients must be free of active infection requiring antibiotics

Exclusion Criteria:

• Patients with bilateral hydronephrosis which cannot be alleviated by ureteral stents or percutaneous drainage

• Patients previously treated with chemotherapy except when used concurrently with radiation therapy

• Patients who have received concurrent paclitaxel and/or concurrent topotecan with radiation therapy are ineligible

• Patients with craniospinal metastases

• Patients with a concomitant malignancy other than non-melanoma skin cancer

• Patients with a prior invasive malignancy (except non-melanoma skin cancer) who have had any evidence of disease within the last 5 years or whose prior malignancy treatment contraindicates the current protocol therapy

• Patients with serious non-healing wound, ulcer, or bone fracture; this includes history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess for which an interval of 3 to 6 months must pass before study entry; in addition, the patient must have undergone correction (or spontaneous healing) of the perforation/fistula and/or the underlying process causing the fistula/perforation; patients with granulating incisions healing by secondary intention with no evidence of fascial dehiscence or infection are eligible but require weekly wound examinations

• Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels

• Patients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of treatment on this study

• Patients with clinically significant cardiovascular disease; this includes:

• Uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 90 mm Hg

• Myocardial infarction or unstable angina < 6 months prior to registration

• New York Heart Association (NYHA) grade II or greater congestive heart failure

• Serious cardiac arrhythmia requiring medication; this does not include asymptomatic, atrial fibrillation with controlled ventricular rate

• CTCAE grade 2 or greater peripheral vascular disease (at least brief [< 24 hours (hrs)]) episodes of ischemia managed non-surgically and without permanent deficit)

• History of CVA within six months

• Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies

• Patients with or with anticipation of invasive procedures as defined below:

• Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to the first date of bevacizumab therapy

• Major surgical procedure anticipated during the course of the study; this includes, but is not limited to abdominal surgery (laparotomy or laparoscopy) prior to disease progression, such as colostomy or enterostomy reversal, interval or secondary cytoreductive surgery, or second look surgery; please consult with the study chair prior to patient entry for any questions related to the classification of surgical procedures

• Core biopsy, within 7 days prior to randomization

• Patients who are pregnant or nursing; bevacizumab should not be administered to pregnant women; bevacizumab should not be administered to nursing women; patients of childbearing potential must agree to use contraceptive measures during study therapy and for at least six months after completion of bevacizumab therapy

• Patients who have received prior therapy with any anti-vascular endothelial growth factor (VEGF) drug, including bevacizumab

• Patients with clinical symptoms or signs of gastrointestinal obstruction and who require parenteral hydration and/or nutrition

• Patients with medical history or conditions not otherwise previously specified which in the opinion of the investigator should exclude participation in this study; the investigator should feel free to consult the Study Chair or Study Co-Chairs for uncertainty in this regard

• Patients with significant peripheral vascular disease

• Patients with pre-existing grade 2 or greater peripheral neuropathy

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma
• Carcinoma, Adenosquamous
• Carcinoma, Squamous Cell
• Cervical Adenocarcinoma
• Cervical Adenosquamous Carcinoma
• Cervical Squamous Cell Carcinoma
• Recurrent Cervical Carcinoma
• Stage IVB Cervical Cancer
• Uterine Cervical Neoplasms

Intervention

Biological:
• Bevacizumab
Given IV

Drug:
• Cisplatin
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Paclitaxel
Given IV

Other:
• Quality-of-Life Assessment
Ancillary studies
• Questionnaire Administration
Ancillary studies

Drug:
• Topotecan Hydrochloride
Given IV

Locations

Country	Name	City	State
Spain	Vall d'Hebron University Hospital	Barcelona
Spain	Hospital Reina Sofia	Cordoba
Spain	Hospital Universitari de Girona Doctor Josep Trueta	Girona
Spain	Hospital Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	M D Anderson International Spain	Madrid
Spain	Hospital Son Llatzer	Palma
Spain	Instituto Valenciano de Oncologia	Valencia
United States	Pali Momi Medical Center	'Aiea	Hawaii
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	Akron General Medical Center	Akron	Ohio
United States	Summa Akron City Hospital/Cooper Cancer Center	Akron	Ohio
United States	Women's Cancer Care Associates LLC	Albany	New York
United States	Southwest Gynecologic Oncology Associates Inc	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	American Fork Hospital	American Fork	Utah
United States	McFarland Clinic PC-William R Bliss Cancer Center	Ames	Iowa
United States	AnMed Health Cancer Center	Anderson	South Carolina
United States	AnMed Health Hospital	Anderson	South Carolina
United States	Michigan Cancer Research Consortium CCOP	Ann Arbor	Michigan
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Hospital District Sixth of Harper County	Anthony	Kansas
United States	Langlade Hospital and Cancer Center	Antigo	Wisconsin
United States	Randolph Hospital	Asheboro	North Carolina
United States	Hope Women's Cancer Centers-Asheville	Asheville	North Carolina
United States	Atlanta Regional CCOP	Atlanta	Georgia
United States	Emory University/Winship Cancer Institute	Atlanta	Georgia
United States	Grady Health System	Atlanta	Georgia
United States	Northside Hospital	Atlanta	Georgia
United States	Piedmont Hospital	Atlanta	Georgia
United States	Saint Joseph's Hospital of Atlanta	Atlanta	Georgia
United States	Georgia Regents University Medical Center	Augusta	Georgia
United States	Colorado Gynecologic Oncology Group	Aurora	Colorado
United States	The Medical Center of Aurora	Aurora	Colorado
United States	University of Colorado Cancer Center - Anschutz Cancer Pavilion	Aurora	Colorado
United States	Well Star Cobb Hospital	Austell	Georgia
United States	University Medical Center Brackenridge	Austin	Texas
United States	Franklin Square Hospital Center	Baltimore	Maryland
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Hematology/Oncology Clinic LLP	Baton Rouge	Louisiana
United States	Woman's Hospital	Baton Rouge	Louisiana
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	Saint Francis Hospital and Health Centers	Beech Grove	Indiana
United States	Mary Rutan Hospital	Bellefontaine	Ohio
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
United States	Saint Luke's University Hospital-Bethlehem Campus	Bethlehem	Pennsylvania
United States	Spectrum Health Big Rapids Hospital	Big Rapids	Michigan
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Frontier Cancer Center and Blood Institute-Billings	Billings	Montana
United States	Montana Cancer Consortium CCOP	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Mid Dakota Clinic	Bismarck	North Dakota
United States	Saint Alexius Medical Center	Bismarck	North Dakota
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Joseph Medical Center	Bloomington	Illinois
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Boulder Community Hospital	Boulder	Colorado
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Island Gynecologic Oncology	Brightwaters	New York
United States	Montefiore Medical Center-Einstein Campus	Bronx	New York
United States	State University of New York Downstate Medical Center	Brooklyn	New York
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Roy and Patricia Disney Family Cancer Center	Burbank	California
United States	Mills - Peninsula Hospitals	Burlingame	California
United States	Cone Health Cancer Center at Alamance Regional	Burlington	North Carolina
United States	Fletcher Allen Health Care-Medical Center	Burlington	Vermont
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Aultman Health Foundation	Canton	Ohio
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	Rocky Mountain Oncology	Casper	Wyoming
United States	Sandra L Maxwell Cancer Center	Cedar City	Utah
United States	Providence Regional Cancer System-Centralia	Centralia	Washington
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	John H Stroger Jr Hospital of Cook County	Chicago	Illinois
United States	Mount Sinai Hospital Medical Center	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	Swedish Covenant Hospital	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	University of Cincinnati	Cincinnati	Ohio
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	South Carolina Oncology Associates PA	Columbia	South Carolina
United States	Columbus CCOP	Columbus	Ohio
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	John B Amos Cancer Center	Columbus	Georgia
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	John Muir Medical Center-Concord Campus	Concord	California
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Clements University Hospital	Dallas	Texas
United States	Parkland Memorial Hospital	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Zale Lipshy University Hospital	Dallas	Texas
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 and Medical Center	Dearborn	Michigan
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Dekalb Medical Center	Decatur	Georgia
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	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 Capitol	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Henry Ford Hospital	Detroit	Michigan
United States	Saint John Hospital and Medical Center	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Greenville Health System Cancer Institute-Easley	Easley	South Carolina
United States	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin
United States	Saint Elizabeth Medical Center South	Edgewood	Kentucky
United States	Fairview-Southdale Hospital	Edina	Minnesota
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Elkhart Clinic	Elkhart	Indiana
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Michiana Hematology Oncology PC-Elkhart	Elkhart	Indiana
United States	Union Hospital of Cecil County	Elkton	Maryland
United States	Rocky Mountain Gynecologic Oncology PC	Englewood	Colorado
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	Saint Francis Hospital	Evanston	Illinois
United States	Highlands Oncology Group PA - Fayetteville	Fayetteville	Arkansas
United States	Piedmont Fayette Hospital	Fayetteville	Georgia
United States	Washington Regional Medical Center - Fayetteville	Fayetteville	Arkansas
United States	Saint Francis Hospital	Federal Way	Washington
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	McLeod Regional Medical Center	Florence	South Carolina
United States	Front Range Cancer Specialists	Fort Collins	Colorado
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Broward Health Medical Center	Fort Lauderdale	Florida
United States	Florida Gynecologic Oncology	Fort Myers	Florida
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana
United States	Baylor All Saints Medical Center at Fort Worth	Fort Worth	Texas
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	California Cancer Center - North Fresno	Fresno	California
United States	Unity Hospital	Fridley	Minnesota
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	Illinois CancerCare Galesburg	Galesburg	Illinois
United States	University of Texas Medical Branch at Galveston	Galveston	Texas
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado
United States	Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan
United States	Mercy Health Saint Mary's	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Berdeaux, Donald MD (UIA Investigator)	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	North Colorado Medical Center	Greeley	Colorado
United States	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin
United States	Saint Mary's Hospital	Green Bay	Wisconsin
United States	Saint Vincent Hospital	Green Bay	Wisconsin
United States	Cone Health Cancer Center	Greensboro	North Carolina
United States	Greenville Health System Cancer Institute-Andrews	Greenville	South Carolina
United States	Greenville Health System Cancer Institute-Butternut	Greenville	South Carolina
United States	Greenville Health System Cancer Institute-Eastside	Greenville	South Carolina
United States	Greenville Health System Cancer Institute-Faris	Greenville	South Carolina
United States	Greenville Memorial Hospital	Greenville	South Carolina
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Self Regional Healthcare	Greenwood	South Carolina
United States	Cancer Centers of the Carolinas-Greer Medical Oncology	Greer	South Carolina
United States	Greenville Health System Cancer Institute-Greer	Greer	South Carolina
United States	Hartford Hospital	Hartford	Connecticut
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	Northern Montana Hospital	Havre	Montana
United States	Saint Peter's Community Hospital	Helena	Montana
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	Sudarshan K Sharma MD Limted-Gynecologic Oncology	Hinsdale	Illinois
United States	Memorial Healthcare System - Joe DiMaggio Children's Hospital	Hollywood	Florida
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Oncare Hawaii Inc-Kuakini	Honolulu	Hawaii
United States	Oncare Hawaii Inc-POB II	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	Baylor College of Medicine	Houston	Texas
United States	Ben Taub General Hospital	Houston	Texas
United States	Lyndon Baines Johnson General Hospital	Houston	Texas
United States	M D Anderson Cancer Center	Houston	Texas
United States	Methodist Hospital	Houston	Texas
United States	Saint Luke's Episcopal Hospital	Houston	Texas
United States	Veterans Administration Medical Center	Houston	Texas
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Franciscan Saint Francis Health-Indianapolis	Indianapolis	Indiana
United States	Gynecologic Oncology of Indiana	Indianapolis	Indiana
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Saint Vincent Hospital and Health Services	Indianapolis	Indiana
United States	Saint Vincent Oncology Center	Indianapolis	Indiana
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan
United States	Allegiance Health	Jackson	Michigan
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Queens Hospital Center	Jamaica	New York
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	Glacier Oncology PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Presence Saint Mary's Hospital	Kankakee	Illinois
United States	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri
United States	North Kansas City Hospital	Kansas City	Missouri
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Joseph Health Center	Kansas City	Missouri
United States	Saint Luke's Cancer Institute	Kansas City	Missouri
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	Truman Medical Center	Kansas City	Missouri
United States	University of Kansas Cancer Center	Kansas City	Kansas
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	Wellmont Holston Valley Hospital and Medical Center	Kingsport	Tennessee
United States	Kinston Medical Specialists PA	Kinston	North Carolina
United States	University of Tennessee - Knoxville	Knoxville	Tennessee
United States	Community Howard Regional Health	Kokomo	Indiana
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	IU Health La Porte Hospital	La Porte	Indiana
United States	Wilford Hall Medical Center	Lackland Air Force Base	Texas
United States	Lakeland Regional Cancer Center	Lakeland	Florida
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Saint Clare Hospital	Lakewood	Washington
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Sparrow Hospital	Lansing	Michigan
United States	Women's Cancer Center of Nevada	Las Vegas	Nevada
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Gwinnett Medical Center	Lawrenceville	Georgia
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	Beebe Medical Center	Lewes	Delaware
United States	Baptist Health Lexington	Lexington	Kentucky
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	Cancer Center of Kansas-Liberal	Liberal	Kansas
United States	Liberty Hospital	Liberty	Missouri
United States	Liberty Radiation Oncology Center	Liberty	Missouri
United States	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii
United States	Saint Rita's Medical Center	Lima	Ohio
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Saint Mary Mercy Hospital	Livonia	Michigan
United States	Logan Regional Hospital	Logan	Utah
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Long Beach Memorial Medical Center-Todd Cancer Institute	Long Beach	California
United States	Longmont United Hospital	Longmont	Colorado
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Los Angeles County-USC Medical Center	Los Angeles	California
United States	UCLA / Jonsson Comprehensive Cancer Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Doctors Carrol, Sheth, Raghavan	Louisville	Kentucky
United States	Norton Hospital Pavilion and Medical Campus	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	Central Georgia Gynecologic Oncology	Macon	Georgia
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	North Shore University Hospital	Manhasset	New York
United States	North Shore-LIJ Health System CCOP	Manhasset	New York
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	Wellstar Kennestone Hospital	Marietta	Georgia
United States	Bay Area Medical Center	Marinette	Wisconsin
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	Saint Joseph's Hospital	Marshfield	Wisconsin
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	Lake University Ireland Cancer Center	Mentor	Ohio
United States	Orange Regional Medical Center	Middletown	New York
United States	Mid-Michigan Medical Center - Midland	Midland	Michigan
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Aurora Sinai Medical Center	Milwaukee	Wisconsin
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	University of Minnesota Medical Center-Fairview	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Michiana Hematology Oncology PC-Mishawaka	Mishawaka	Indiana
United States	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana
United States	Community Medical Hospital	Missoula	Montana
United States	Guardian Oncology and Center for Wellness	Missoula	Montana
United States	Montana Cancer Specialists	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	University of South Alabama Mitchell Cancer Institute	Mobile	Alabama
United States	Holy Family Medical Center	Monmouth	Illinois
United States	Illinois CancerCare-Monmouth	Monmouth	Illinois
United States	Morristown Memorial Hospital	Morristown	New Jersey
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	Palo Alto Medical Foundation-Gynecologic Oncology	Mountain View	California
United States	D N Greenwald Center	Mukwonago	Wisconsin
United States	The Community Hospital	Munster	Indiana
United States	Intermountain Medical Center	Murray	Utah
United States	Mercy Health Mercy Campus	Muskegon	Michigan
United States	Meharry Medical College	Nashville	Tennessee
United States	Tennessee Oncology PLLC- Centennial Medical Center	Nashville	Tennessee
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	Jersey Shore Medical Center	Neptune	New Jersey
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	North Shore-LIJ Health System/Center for Advanced Medicine	New Hyde Park	New York
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	Tulane University Health Sciences Center	New Orleans	Louisiana
United States	Beth Israel Medical Center	New York	New York
United States	Columbia University Medical Center	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	New York University Langone Medical Center	New York	New York
United States	Saint Luke's Roosevelt Hospital Center - Saint Luke's Division	New York	New York
United States	Weill Medical College of Cornell University	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Licking Memorial Hospital	Newark	Ohio
United States	UMDNJ - New Jersey Medical School	Newark	New Jersey
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	Michiana Hematology Oncology PC-Niles	Niles	Michigan
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	Southwest VA Regional Cancer Center	Norton	Virginia
United States	Sutter Cancer Research Consortium	Novato	California
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	Oconomowoc Memorial Hospital-ProHealth Care Inc	Oconomowoc	Wisconsin
United States	Green Bay Oncology - Oconto Falls	Oconto Falls	Wisconsin
United States	McKay-Dee Hospital Center	Ogden	Utah
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Providence - Saint Peter Hospital	Olympia	Washington
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Saint Joseph Hospital - Orange	Orange	California
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	Florida Hospital Orlando	Orlando	Florida
United States	UF Cancer Center at Orlando Health	Orlando	Florida
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois
United States	Menorah Medical Center	Overland Park	Kansas
United States	Saint Luke's South Hospital	Overland Park	Kansas
United States	Stanford Cancer Institute	Palo Alto	California
United States	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Advocate Lutheran General Hospital.	Park Ridge	Illinois
United States	Parker Adventist Hospital	Parker	Colorado
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Singing River Hospital	Pascagoula	Mississippi
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	Illinois Valley Hospital	Peru	Illinois
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	The Women's Institute for Gynecologic Cancer and Special Pelvic Surgery	Phillipsburg	New Jersey
United States	Saint Joseph's Hospital and Medical Center	Phoenix	Arizona
United States	Pikeville Medical Center	Pikeville	Kentucky
United States	UPMC-Magee Womens Hospital	Pittsburgh	Pennsylvania
United States	West Penn Hospital	Pittsburgh	Pennsylvania
United States	Michiana Hematology Oncology PC-Plymouth	Plymouth	Indiana
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Saint Joseph Mercy Port Huron	Port Huron	Michigan
United States	Maine Medical Center-Bramhall Campus	Portland	Maine
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Kansas City CCOP	Prairie Village	Kansas
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	Women and Infants Hospital	Providence	Rhode Island
United States	Utah Valley Regional Medical Center	Provo	Utah
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	MultiCare Good Samaritan Hospital	Puyallup	Washington
United States	Black Hills Obstetrics and Gynecology	Rapid City	South Dakota
United States	Annie Penn Memorial Hospital	Reidsville	North Carolina
United States	Center of Hope at Renown Medical Center	Reno	Nevada
United States	Renown Regional Medical Center	Reno	Nevada
United States	Marshfield Clinic at James Beck Cancer Center	Rhinelander	Wisconsin
United States	Marshfield Clinic-Rice Lake Center	Rice Lake	Wisconsin
United States	Reid Hospital and Health Care Services	Richmond	Indiana
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Valley Hospital	Ridgewood	New Jersey
United States	Southern Regional Medical Center	Riverdale	Georgia
United States	Carilion Clinic Gynecological Oncology	Roanoke	Virginia
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Mayo Clinic	Rochester	Minnesota
United States	Phelps County Regional Medical Center	Rolla	Missouri
United States	Harbin Clinic Medical Oncology and Clinical Research	Rome	Georgia
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	Rutherford Hospital	Rutherfordton	North Carolina
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Saint Mary's of Michigan	Saginaw	Michigan
United States	Dixie Medical Center Regional Cancer Center	Saint George	Utah
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Lakeland Hospital	Saint Joseph	Michigan
United States	Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Saint Joseph Oncology Inc	Saint Joseph	Missouri
United States	Saint Louis University Hospital	Saint Louis	Missouri
United States	Metro-Minnesota NCI Community Oncology Research Program	Saint Louis Park	Minnesota
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Intermountain Health Care	Salt Lake City	Utah
United States	LDS Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists-Salt Lake City	Salt Lake City	Utah
United States	University of California San Diego	San Diego	California
United States	California Pacific Medical Center-Pacific Campus	San Francisco	California
United States	UCSF Medical Center-Mount Zion	San Francisco	California
United States	Sarasota Memorial Hospital	Sarasota	Florida
United States	Memorial University Medical Center	Savannah	Georgia
United States	Greenville Health System Cancer Institute-Seneca	Seneca	South Carolina
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Shawnee Mission Medical Center	Shawnee Mission	Kansas
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Highland Clinic	Shreveport	Louisiana
United States	Louisiana State University Health Sciences Center Shreveport	Shreveport	Louisiana
United States	Mercy Medical Center-Sioux City	Sioux City	Iowa
United States	Saint Luke's Regional Medical Center	Sioux City	Iowa
United States	Avera Cancer Institute	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	Memorial Hospital of South Bend	South Bend	Indiana
United States	Michiana Hematology Oncology PC-South Bend	South Bend	Indiana
United States	Northern Indiana Cancer Research Consortium CCOP	South Bend	Indiana
United States	South Bend Clinic	South Bend	Indiana
United States	Providence Hospital	Southfield	Michigan
United States	Greenville Health System Cancer Institute-Spartanburg	Spartanburg	South Carolina
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	Upstate Carolina CCOP	Spartanburg	South Carolina
United States	Illinois CancerCare-Spring Valley	Spring Valley	Illinois
United States	Baystate Medical Center	Springfield	Massachusetts
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-Cancer Research for The Ozarks Springfield	Springfield	Missouri
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Marshfield Clinic Cancer Care at Saint Michael's Hospital	Stevens Point	Wisconsin
United States	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	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Overlook Hospital	Summit	New Jersey
United States	Olive View-University of California Los Angeles Medical Center	Sylmar	California
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	MultiCare Allenmore Hospital	Tacoma	Washington
United States	Multicare Health System	Tacoma	Washington
United States	Northwest CCOP	Tacoma	Washington
United States	Saint Joseph Medical Center	Tacoma	Washington
United States	Moffitt Cancer Center	Tampa	Florida
United States	Scott and White Memorial Hospital	Temple	Texas
United States	North Suburban Medical Center	Thornton	Colorado
United States	Munson Medical Center	Traverse City	Michigan
United States	Upper Valley Medical Center	Troy	Ohio
United States	Tulsa Cancer Institute	Tulsa	Oklahoma
United States	Vince Lombardi Cancer Clinic	Two Rivers	Wisconsin
United States	Sutter Solano Medical Center/Cancer Center	Vallejo	California
United States	Inspira Medical Center Vineland	Vineland	New Jersey
United States	Virtua West Jersey Hospital Voorhees	Voorhees	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Maui Memorial Medical Center	Wailuku	Hawaii
United States	Pacific Cancer Institute of Maui	Wailuku	Hawaii
United States	John Muir Medical Center-Walnut Creek	Walnut Creek	California
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Cadence Cancer Center in Warrenville	Warrenville	Illinois
United States	Washington Hospital Center	Washington	District of Columbia
United States	Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	Aspirus Regional Cancer Center	Wausau	Wisconsin
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Aurora West Allis Medical Center	West Allis	Wisconsin
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	Michiana Hematology Oncology-PC Westville	Westville	Indiana
United States	Exempla Lutheran Medical Center	Wheat Ridge	Colorado
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	Rice Memorial Hospital	Willmar	Minnesota
United States	Clinton Memorial Hospital	Wilmington	Ohio
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Minnesota Oncology and Hematology PA-Woodbury	Woodbury	Minnesota
United States	University of Massachusetts Memorial Health Care	Worcester	Massachusetts
United States	Lankenau Medical Center	Wynnewood	Pennsylvania
United States	Mainline Health CCOP	Wynnewood	Pennsylvania
United States	Metro Health Hospital	Wyoming	Michigan
United States	Greene Memorial Hospital	Xenia	Ohio
United States	Genesis HealthCare System	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	NRG Oncology

Countries where clinical trial is conducted

United States,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Extent of Nicotine Dependence	Assessed from answers the patients provide to a questionnaire. Will be assessed for associations with progression and/or death.	Up to 5 years
Other	Health-related Quality of Life	Assessed by FACT-Cx TOI; FACT/GOG-Ntx4 subscale; and BPI at baseline, before courses 2 and 5, and at 6 and 9 months after course 1. The linear mixed model will be used to evaluate the hypotheses on FACT-Cx TOI score, adjusting for baseline FACT-Cx TOI scores and age. A mixed-effects mixed-distribution model will be considered to analyze NTx4 subscale scores and the BPI score. 95% confidence intervals will be reported for the estimated treatment differences of BPI score.	Up to 9 months after course 1
Other	Levels of Angiogenesis Markers in Plasma	Associations between biomarkers and overall survival or progression-free survival will be examined in a Cox proportional hazards model that includes significant prognostic variables based on prior research such as performance status, prior cisplatin therapy, and stage of disease. Logistic regression will be used to help assess the value of biomarkers in predicting response to a particular treatment or determine associations with response.	Up to 5 years
Other	Levels of Cell-free DNA in Plasma	Associations between biomarkers and overall survival or progression-free survival will be examined in a Cox proportional hazards model that includes significant prognostic variables based on prior research such as performance status, prior cisplatin therapy, and stage of disease. Logistic regression will be used to help assess the value of biomarkers in predicting response to a particular treatment or determine associations with response.	Up to 5 years
Other	Levels of Tumor Measures of Angiogenesis	Associations between biomarkers and overall survival or progression-free survival will be examined in a Cox proportional hazards model that includes significant prognostic variables based on prior research such as performance status, prior cisplatin therapy, and stage of disease. Logistic regression will be used to help assess the value of biomarkers in predicting response to a particular treatment or determine associations with response.	Up to 5 years
Other	Number of CTCs	Associations between biomarkers and overall survival or progression-free survival will be examined in a Cox proportional hazards model that includes significant prognostic variables based on prior research such as performance status, prior cisplatin therapy, and stage of disease. Logistic regression will be used to help assess the value of biomarkers in predicting response to a particular treatment or determine associations with response.	Up to 5 years
Other	Prevalence of Active Smoking	An estimate of the prevalence of active smoking will be calculated. Will be assessed for associations with progression and/or death.	Up to 5 years
Primary	Overall Survival	The observed length of life from randomization into the study to death or the date of last contact.	From entry into the study to death or the date of last contact, assessed up to 5 years
Primary	Progression-free Survival	Disease that can be assessed clinically (physical examination) should be evaluated every cycle (every 3 weeks). Disease assessed by imaging modalities (CXR, CT, MRI) should be evaluated every other cycle unless other evidence of a change mandates earlier assessment. Tumor measurements should also be done after the final cycle (if the patient is taken off of study therapy for a reason other than progression) and then every 3 months x 2 years (followed with every 6 months x 3 years) until progression is documented. "Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions assessed radiographically and 50% increase if the only target lesion is a solitary pelvic mass measured by physical exam, or unequivocal progression of a non-target lesion, or the appearance of new lesions", or similar definition as accurate and appropriate.	From study entry until disease progression, death or date of last contact, assessed up to 5 years (During treatment: every 3 weeks if by physical exam, every 6 weeks by CXR, CT or MRI. In follow-up: quarterly for 2 years then semi-annually for 3 years)
Primary	Tumor Response	Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions by CT, MRI or CXR. If the only target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% increase in longest diameter is required; Overall Response (OR) = CR + PR.	Every cycle (if assessed by physical exam), every other cycle (if assessed by imaging), after the final cycle, then every 3 months x 2 years, then every 6 months x 3 years up to 5 years.
Primary	To Determine and Compare the Frequency and Severity of Adverse Events as Assessed by CTCAE Version 3.0 for the Regimens Administered on This Study.	The number of patients on each arm who have Grade 3 AE or higher toxicity.	From date of enrollment until 30 days after treatment completion