Bevacizumab, Radiation Therapy, and Cisplatin in Treating Patients With Previously Untreated Locally Advanced Cervical Cancer

A PHASE II STUDY OF BEVACIZUMAB IN COMBINATION WITH DEFINITIVE RADIOTHERAPY AND CISPLATIN CHEMOTHERAPY IN UNTREATED PATIENTS WITH LOCALLY ADVANCED CERVICAL CARCINOMA

This phase II trial is studying how well giving bevacizumab together with radiation therapy and cisplatin works in treating patients with previously untreated locally advanced cervical cancer. Monoclonal antibodies, such as bevacizumab, 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. Bevacizumab may also stop the growth of cervical cancer by blocking blood flow to the tumor. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with radiation therapy and cisplatin may kill more tumor cells.

Study Overview

• Status: Completed
• Conditions: Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IIA Cervical Cancer AJCC v7; Stage IIB Cervical Cancer AJCC v6 and v7; Stage III Cervical Cancer AJCC v6 and v7; Stage IB Cervical Cancer AJCC v6 and v7
• Intervention / Treatment: Drug: Cisplatin; Radiation: External Beam Radiation Therapy; Biological: Bevacizumab; Radiation: Internal Radiation Therapy

Detailed Description

PRIMARY OBJECTIVES:

I. Determine treatment-related serious adverse-event rates and adverse-event rates within the first 90 days from treatment start in patients with previously untreated locally advanced carcinoma of the cervix treated with bevacizumab, cisplatin, and concurrent pelvic radiotherapy.

SECONDARY OBJECTIVES:

I. Evaluate treatment-related serious adverse events and adverse events at any time.

II. Evaluate disease-free survival (local, regional, or distant failure, or death due to any cause).

III. Evaluate overall survival (death due to any cause). IV. Implement the image-based brachytherapy guidelines proposed by the Transatlantic Image-Guided Brachytherapy Working Group.

V. Collect CT scan or MRI-based dosimetry of brachytherapy applications used during the course of treatment for later analysis of feasibility and consistency as well as dose/volume assessments of tumor control and complications.

OUTLINE: This is a multicenter study.

Patients undergo pelvic external-beam radiotherapy (EBRT) once daily, 5 days a week, for 5 weeks for a total of 45 Gy.

Some patients also undergo low-dose rate brachytherapy twice, 1-3 weeks apart, beginning >= 4 weeks after initiating EBRT or high-dose rate brachytherapy 5 times, >= 48 hours apart, beginning >= 2 weeks after initiating EBRT. EBRT and chemotherapy are halted on the day of high-dose rate brachytherapy. Patients receive bevacizumab IV over 30-90 minutes on days 1, 15, and 29 and cisplatin IV over 60 minutes on days 1, 8, 15, 22, 29, and 35.

After completion of study treatment, patients are followed periodically.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program
  • Quebec
    • Montreal, Quebec, Canada, H2W 1S6
      • McGill University Department of Oncology
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre
• United States
  • California
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Penrose-Saint Francis Healthcare
    • Denver, Colorado, United States, 80217-3364
      • University of Colorado
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Baptist MD Anderson Cancer Center
    • Jacksonville, Florida, United States, 32209
      • University of Florida Health Science Center - Jacksonville
    • Jacksonville, Florida, United States, 32258
      • Baptist Medical Center South
    • Jacksonville, Florida, United States, 32207
      • Integrated Community Oncology Network-Southside Cancer Center
    • Jacksonville Beach, Florida, United States, 32250
      • Integrated Community Oncology Network-Florida Cancer Center Beaches
    • Orange Park, Florida, United States, 32073
      • 21st Century Oncology-Orange Park
    • Orlando, Florida, United States, 32806
      • UF Cancer Center at Orlando Health
    • Palatka, Florida, United States, 32177
      • 21st Century Oncology-Palatka
    • Panama City, Florida, United States, 32401
      • Bay Medical Center
    • Saint Augustine, Florida, United States, 32086
      • Integrated Community Oncology Network-Flager Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital/Winship Cancer Institute
    • Atlanta, Georgia, United States, 30303
      • Grady Health System
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
      • Northwest Community Hospital
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60612
      • John H Stroger Jr Hospital of Cook County
    • Olympia Fields, Illinois, United States, 60461
      • Franciscan St. James Health-Olympia Fields Campus
    • Peoria, Illinois, United States, 61603
      • Methodist Medical Center of Illinois
  • Indiana
    • Anderson, Indiana, United States, 46016
      • Saint Vincent Anderson Regional Hospital/Cancer Center
    • Beech Grove, Indiana, United States, 46107
      • Franciscan Saint Francis Health-Beech Grove
    • Indianapolis, Indiana, United States, 46260
      • Saint Vincent Hospital and Health Care Center
    • Richmond, Indiana, United States, 47374
      • Reid Health
  • Kansas
    • Kansas City, Kansas, United States, 66112
      • Providence Medical Center
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Overland Park, Kansas, United States, 66209
      • Menorah Medical Center
    • Overland Park, Kansas, United States, 66213
      • Saint Luke's South Hospital
    • Overland Park, Kansas, United States, 66210
      • Radiation Oncology Practice Corporation Southwest
    • Shawnee Mission, Kansas, United States, 66204
      • Shawnee Mission Medical Center-KCCC
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Baptist Health Lexington
    • Louisville, Kentucky, United States, 40207
      • Norton Suburban Hospital and Medical Campus
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49001
      • Borgess Medical Center
  • Missouri
    • Cape Girardeau, Missouri, United States, 63703
      • Cape Radiation Oncology
    • Independence, Missouri, United States, 64057
      • Centerpoint Medical Center LLC
    • Kansas City, Missouri, United States, 64116
      • North Kansas City Hospital
    • Kansas City, Missouri, United States, 64111
      • Saint Luke'S Hospital of Kansas City
    • Kansas City, Missouri, United States, 64132
      • Research Medical Center
    • Kansas City, Missouri, United States, 64108
      • Truman Medical Center
    • Kansas City, Missouri, United States, 64114
      • Saint Joseph Health Center
    • Kansas City, Missouri, United States, 64114
      • Radiation Oncology Practice Corporation South
    • Kansas City, Missouri, United States, 64154
      • Radiation Oncology Practice Corporation - North
    • Lee's Summit, Missouri, United States, 64086
      • Saint Luke's East - Lee's Summit
    • Liberty, Missouri, United States, 64068
      • Liberty Radiation Oncology Center
    • Saint Joseph, Missouri, United States, 64506
      • Heartland Regional Medical Center
  • Nebraska
    • Kearney, Nebraska, United States, 68847
      • CHI Health Good Samaritan
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • University Medical Center of Southern Nevada
  • New Jersey
    • Livingston, New Jersey, United States, 07039
      • Saint Barnabas Medical Center
    • Long Branch, New Jersey, United States, 07740
      • Monmouth Medical Center
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
    • Newark, New Jersey, United States, 07112
      • Newark Beth Israel Medical Center
  • New York
    • Brooklyn, New York, United States, 11215
      • New York-Presbyterian/Brooklyn Methodist Hospital
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • Rochester, New York, United States, 14642
      • University of Rochester
    • Rochester, New York, United States, 14620
      • Highland Hospital
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Akron, Ohio, United States, 44304
      • Summa Akron City Hospital/Cooper Cancer Center
    • Barberton, Ohio, United States, 44203
      • Summa Barberton Hospital
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital - Dayton
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Samaritan North Health Center
    • Dayton, Ohio, United States, 45405
      • Grandview Hospital
    • Dayton, Ohio, United States, 45428
      • Veteran Affairs Medical Center
    • Findlay, Ohio, United States, 45840
      • Blanchard Valley Hospital
    • Franklin, Ohio, United States, 45005-1066
      • Atrium Medical Center-Middletown Regional Hospital
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Salem, Ohio, United States, 44460
      • Cancer Care Center, Incorporated
    • Troy, Ohio, United States, 45373
      • Upper Valley Medical Center
    • Wilmington, Ohio, United States, 45177
      • Clinton Memorial Hospital
    • Wooster, Ohio, United States, 44691
      • Cancer Treatment Center
    • Wright-Patterson Air Force Base, Ohio, United States, 45433-5529
      • Wright-Patterson Medical Center
    • Xenia, Ohio, United States, 45385
      • Greene Memorial Hospital
  • Pennsylvania
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Bryn Mawr Hospital
    • Paoli, Pennsylvania, United States, 19301
      • Paoli Memorial Hospital
    • Philadelphia, Pennsylvania, United States, 19141
      • Einstein Medical Center Philadelphia
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hospital
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Medical Center
    • Wynnewood, Pennsylvania, United States, 19096
      • Main Line Health NCORP
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Wellmont Holston Valley Hospital and Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center
  • Utah
    • American Fork, Utah, United States, 84003
      • American Fork Hospital / Huntsman Intermountain Cancer Center
    • Cedar City, Utah, United States, 84720
      • Sandra L Maxwell Cancer Center
    • Logan, Utah, United States, 84321
      • Logan Regional Hospital
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center
    • Murray, Utah, United States, 84107
      • Cottonwood Hospital Medical Center
    • Ogden, Utah, United States, 84403
      • McKay-Dee Hospital Center
    • Provo, Utah, United States, 84604
      • Utah Valley Regional Medical Center
    • Saint George, Utah, United States, 84770
      • Dixie Medical Center Regional Cancer Center
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists-Salt Lake City
    • Salt Lake City, Utah, United States, 84143
      • LDS Hospital
    • Salt Lake City, Utah, United States, 84103
      • Intermountain Health Care
  • Virginia
    • Norton, Virginia, United States, 24273
      • Southwest VA Regional Cancer Center
  • Washington
    • Yakima, Washington, United States, 98902
      • North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Medical Center
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert and The Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Histologically confirmed squamous cell, adenocarcinoma, or adenosquamous cell carcinoma of the uterine cervix, meeting 1 of the following stage criteria:

  • Stage IIB-IIIB lymph nodes
  • Stage IB-IIA disease with biopsy-proven pelvic node metastases and/or tumor size >= 5 cm
• No positive para-aortic lymph nodes
• Zubrod performance status 0-2
• WBC >= 3,000/mm^3
• Absolute granulocyte count >= 1,500/mm^3
• Platelet count >= 100,000/mm^3
• INR < 1.5
• Total bilirubin =< 1.5 mg/dL
• Serum creatinine =< 1.5 mg/dL
• AST and ALT =< 2.5 times upper limit of normal (ULN)
• Serum calcium =< 1.3 times ULN
• Hemoglobin >= 10 g/dL (transfusion allowed)
• Urine protein:creatinine ratio ? 0.5 OR urine protein < 1,000 mg by 24-hour urine collection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

• None of the following illnesses or conditions:

  • Medical illness preventing the use of full-dose chemotherapy
  • Evidence of bleeding diathesis or coagulopathy
  • Prior medical or psychiatric illness that would prevent informed consent or limit survival to < 6 months
  • History of aneurysms, cerebrovascular accident, or arteriovenous malformations
  • Active gastrointestinal (GI) ulcers, GI bleeding, or active inflammatory bowel disease
  • Serious, nonhealing wound, ulcer, or current healing fracture
  • History of any type of fistula or GI perforation
  • Intra-abdominal abscess within the past 6 months
• No prior invasive malignancy (except nonmelanomatous skin cancer) unless disease free for >= 3 years
• No significant traumatic injury within the past 28 days

• No clinically significant cardiovascular disease, such as the following:

  • Uncontrolled hypertension (blood pressure > 160/90 mm Hg on medication)
  • Myocardial infarction within the past 12 months
  • Unstable angina within the past 12 months
  • New York Heart Association class II-IV congestive heart failure
  • Unstable symptomatic arrhythmia requiring medication (i.e., chronic atrial arrhythmia, atrial fibrillation, or paroxysmal supraventricular tachycardia)
  • Arterial thromboembolic events, including transient ischemic attack or clinically significant peripheral artery disease, within the past 6 months
• Arterial thromboembolic events, including transient ischemic attack or clinically significant peripheral artery disease, within the past 6 months
• No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
• No known HIV
• No prior organ transplant
• No prior surgery for carcinoma of the cervix other than biopsy
• No prior surgical debulking of pelvic or para-aortic nodes
• No prior pelvic radiotherapy, including transvaginal irradiation to control bleeding
• No prior systemic chemotherapy
• No major surgical procedure or open biopsy within the past 28 days or anticipation of need for major surgical procedure during the course of the study
• No fine needle aspirations or core biopsies within the past 7 days
• No concurrent major surgical procedure
• No concurrent epoetin alfa or Hypericum perforatum (St. John's wort)
• No concurrent intensity-modulated radiotherapy
• No concurrent transvaginal irradiation to control bleeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (radiation therapy, bevacizumab, cisplatin); Patients undergo pelvic EBRT once daily, 5 days a week, for 5 weeks for a total of 45 Gy. Some patients also undergo low-dose rate brachytherapy twice, 1-3 weeks apart, beginning >= 4 weeks after initiating EBRT or high-dose rate brachytherapy 5 times, >= 48 hours apart, beginning >= 2 weeks after initiating EBRT. EBRT and chemotherapy are halted on the day of high-dose rate brachytherapy. Patients receive bevacizumab IV over 30-90 minutes on days 1, 15, and 29 and cisplatin IV over 60 minutes on days 1, 8, 15, 22, 29, and 35.

Drug: Cisplatin; Given IV; Other Names: CDDP; Cis-diamminedichloridoplatinum; Cismaplat; Cisplatinum; Neoplatin; Platinol; Abiplatin; Blastolem; Briplatin; Cis-diammine-dichloroplatinum; Cis-diamminedichloro Platinum (II); Cis-diamminedichloroplatinum; Cis-dichloroammine Platinum (II); Cis-platinous Diamine Dichloride; Cis-platinum; Cis-platinum II; Cis-platinum II Diamine Dichloride; Cisplatina; Cisplatyl; Citoplatino; Citosin; Cysplatyna; DDP; Lederplatin; Metaplatin; Peyrone's Chloride; Peyrone's Salt; Placis; Plastistil; Platamine; Platiblastin; Platiblastin-S; Platinex; Platinol- AQ; Platinol-AQ; Platinol-AQ VHA Plus; Platinoxan; Platinum; Platinum Diamminodichloride; Platiran; Platistin; Platosin; Radiation: External Beam Radiation Therapy; Undergo EBRT; Other Names: EBRT; Definitive Radiation Therapy; External Beam Radiotherapy; External Beam RT; external radiation; External Radiation Therapy; external-beam radiation; Biological: Bevacizumab; Given IV; Other Names: Avastin; Anti-VEGF; Anti-VEGF Humanized Monoclonal Antibody; Anti-VEGF rhuMAb; Bevacizumab Biosimilar BEVZ92; Bevacizumab Biosimilar BI 695502; Bevacizumab Biosimilar CBT 124; Bevacizumab Biosimilar FKB238; Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer; Recombinant Humanized Anti-VEGF Monoclonal Antibody; rhuMab-VEGF; BEVACIZUMAB, LICENSE HOLDER UNSPECIFIED; Radiation: Internal Radiation Therapy; Undergo brachytherapy; Other Names: Internal Radiation Brachytherapy; Radiation Brachytherapy; BRACHYTHERAPY; internal radiation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Treatment-related Serious Adverse Events (SAEs) and Adverse Events (AEs) as Assessed by CTCAE v. 3.0 Criteria Within the First 90 Days From Treatment Start.	Adverse events (AEs) graded using CTCAE v3.0. Grade (Gr) refers to the severity of the AE and assigns Gr 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: 1= Mild AE, 2= Moderate AE, 3= Severe AE, 4= Life-threatening or disabling AE, 5= Death related to AE. Treatment-related SAEs defined as Grade (Gr) >= 4 vaginal bleeding, Gr >=4 thrombotic event, Gr >=3 arterial event, gastrointestinal (GI) bleeding , or bowel/bladder perforation, and any Gr 5 treatment-related AE. Treatment-related AEs defined as all SAEs, Gr 3-4 nausea, vomiting, or diarrhea persisting for >2 weeks despite medical intervention, Gr 4 neutropenia or leukopenia persisting for >7 days, febrile neutropenia defined as a temperature >38.5 degree Celsius and granulocytes < 1000/mm3, Grade 3-4 hematologic toxicity with the exception of neutropenia and leukopenia, and Grade 3-4 GI, renal, cardiac, pulmonary, hepatic, or neurologic AEs.	From start of treatment to 90 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Treatment-related SAEs and AEs as Assessed by CTCAE v. 3.0 Criteria at Any Time.	Adverse events (AEs) graded using CTCAE v3.0. Grade (Gr) refers to the severity of the AE and assigns Gr 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: 1= Mild AE, 2= Moderate AE, 3= Severe AE, 4= Life-threatening or disabling AE, 5= Death related to AE. Treatment-related SAEs defined as Gr >= 4 vaginal bleeding, Gr >=4 thrombotic event, Gr >=3 arterial event, gastrointestinal (GI) bleeding , or bowel/bladder perforation, and any Gr 5 treatment-related AE. Treatment-related AEs defined as all SAEs, Gr 3-4 nausea, vomiting, or diarrhea persisting for >2 weeks despite medical intervention, Gr 4 neutropenia or leukopenia persisting for >7 days, febrile neutropenia defined as a temperature >38.5 degree Celsius and granulocytes < 1000/mm3, Grade 3-4 hematologic toxicity with the exception of neutropenia and leukopenia, and Grade 3-4 GI, renal, cardiac, pulmonary, hepatic, or neurologic AEs.	From start of treatment to last follow-up, up to 6.0 years. Analysis occurred after all patients had been on study for at least 2 years.
Disease-free Survival (Three-year Rate Reported)	Failure is defined as local, regional, or distant disease, or death due to any cause. Disease-free survival time is defined as time from registration to the date of failure and disease-free survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive and disease-free are censored at the date of last contact.	From registration to 3 years
Overall Survival (Three-year Rate Reported)	Overall survival time is defined as time from registration to the date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.	From registration to 3 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Collaborators: Radiation Therapy Oncology Group
• Investigators: Principal Investigator: Tracey Schefter, Radiation Therapy Oncology Group

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2006
• Primary Completion (Actual): June 4, 2010
• Study Completion (Actual): December 15, 2016

Study Registration Dates

• First Submitted: August 24, 2006
• First Submitted That Met QC Criteria: August 24, 2006
• First Posted (Estimate): August 29, 2006

Study Record Updates

• Last Update Posted (Actual): March 20, 2018
• Last Update Submitted That Met QC Criteria: February 21, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Neoplasms, Complex and Mixed; Neoplasms, Squamous Cell; Uterine Cervical Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Carcinoma, Adenosquamous; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Antibodies; Cisplatin; Immunoglobulins; Bevacizumab; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Immunoglobulin G; Endothelial Growth Factors
• Other Study ID Numbers: NCI-2009-00722 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA021661 (U.S. NIH Grant/Contract); CDR0000493005; RTOG 0417 (Other Identifier: Radiation Therapy Oncology Group); RTOG-0417 (Other Identifier: CTEP)