Cisplatin and Radiation Therapy With or Without Tirapazamine in Treating Patients With Cervical Cancer

A Phase III, Randomized Trial of Weekly Cisplatin and Radiation Versus Cisplatin and Tirapazamine and Radiation in Stage IB2, IIA, IIIB and IVA Cervical Carcinoma Limited to the Pelvis

This randomized phase III trial is studying cisplatin, radiation therapy, and tirapazamine to see how well they work compared to cisplatin and radiation therapy in treating patients with cervical cancer. Drugs used in chemotherapy, such as cisplatin and tirapazamine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Internal radiation uses radioactive material placed directly into or near a tumor to kill tumor cells. Cisplatin and tirapazamine may make tumor cells more sensitive to radiation therapy. It is not yet known whether giving cisplatin together with radiation therapy is more effective with or without tirapazamine in treating cervical cancer.

Study Overview

• Status: Terminated
• Conditions: Cervical Adenocarcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer; Cervical Adenosquamous Cell Carcinoma
• Intervention / Treatment: Drug: cisplatin; Drug: tirapazamine

Detailed Description

PRIMARY OBJECTIVE:

I. Compare the progression-free survival of patients with stage IB, IIA, IIB, IIIB, or IVA carcinoma of the cervix treated with cisplatin and radiotherapy with vs without tirapazamine.

SECONDARY OBJECTIVES:

I. Compare overall survival of patients treated with these regimens. II. Compare the toxicity of these regimens in these patients.

TERTIARY OBJECTIVES:

I. Correlate study treatment with tumor expression of carbonic anhydrase IX (CA-IX) and recurrence-free survival, overall survival, or metastasis in patients treated with these regimens.

II. Correlate expression of CA-IX, hypoxia inducible factor-1α, CD-31, thrombospondin-1, CD-105, or vascular endothelial growth factor (VEGF) in primary tumor tissue with recurrence-free survival, overall survival, or metastasis in patients treated with these regimens.

III. Correlate pre-treatment and/or post-treatment serum concentrations of angiogenic markers including angiogenin or VEGF with recurrence-free survival, overall survival, or metastasis in patients treated with these regimens.

IV. Correlate various combinations of biological markers of hypoxia and angiogenesis with recurrence-free survival, overall survival, or metastasis in patients treated with these regimens.

V. Correlate levels of individual biological markers of hypoxia or angiogenesis with clinicopathological characteristics including tumor size, histologic subtype, FIGO stage, depth of invasion, pelvic node status, site of recurrence, and hemoglobin level as well as patient, age, race and performance status in patients treated with these regimens.

OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to FIGO stage of disease (IB2 vs IIA vs IIB vs IIIB vs IVA), brachytherapy method (low-dose rate vs high-dose rate), surgical staging of para-aortic nodes (yes vs no). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive cisplatin IV over 30-60 minutes once weekly on days 1, 8, 15, 22, 29, and 36 (weeks 1-6). Patients also undergo external beam radiotherapy to the pelvis once daily on days 1-5, 8-12, 15-19, 22-26, and 29-33 (weeks 1-5). Patients then receive either 1 or 2 applications of low-dose rate brachytherapy in weeks 6-8 OR 5 applications of high-dose rate (HDR)* brachytherapy once weekly in weeks 4-8 and 3-5 days of parametrial boost radiotherapy** beginning after the first brachytherapy implant. Treatment continues in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive tirapazamine IV over 2 hours on days 1, 8, 10, 12, 15, 22, 24, 26, and 29 and cisplatin IV over 1 hour on days 1, 15, and 29. Patients also undergo radiotherapy and brachytherapy as in arm I. Treatment continues in the absence of disease progression or unacceptable toxicity.

NOTE: *No external beam radiotherapy is administered on the day of HDR brachytherapy. If the majority of external beam radiotherapy has been administered, HDR brachytherapy may be administered in 2 applications per week (separated by at least 72 hours) in order to complete all treatment within 8 weeks.

NOTE: ** Patients may receive a parametrial boost at the discretion of the treating radiation oncologist.

After completion of study treatment, patients are followed for at least 5 years.

• Study Type: Interventional
• Enrollment (Actual): 402
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
  • British Columbia
    • Surrey, British Columbia, Canada, V3V 1Z2
      • BCCA-Fraser Valley Cancer Centre
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BCCA-Vancouver Cancer Centre
  • Ontario
    • Sudbury, Ontario, Canada, P3E 5J1
      • Health Sciences North
    • Thunder Bay, Ontario, Canada, P7B 6V4
      • Thunder Bay Regional Health Science Centre
    • Toronto, Ontario, Canada, M4N 3M5
      • Odette Cancer Centre- Sunnybrook Health Sciences Centre
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
      • CHUM - Hopital Notre-Dame
    • Quebec City, Quebec, Canada, G1R 2J6
      • CHUQ - Pavilion Hotel-Dieu de Quebec
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
    • Mobile, Alabama, United States, 36607
      • Mobile Infirmary Medical Center
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Providence Alaska Medical Center
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner Good Samaritan Medical Center
    • Phoenix, Arizona, United States, 85006
      • Western Regional CCOP
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group PA - Fayetteville
    • Fayetteville, Arkansas, United States, 72703
      • Washington Regional Medical Center - Fayetteville
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Castro Valley, California, United States, 94546
      • East Bay Radiation Oncology Center
    • Duarte, California, United States, 91010
      • City of Hope Medical Center
    • Los Angeles, California, United States, 90095
      • Jonsson Comprehensive Cancer Center
    • Oakland, California, United States, 94609
      • Bay Area Tumor Institute CCOP
    • Orange, California, United States, 92868
      • University of California Medical Center At Irvine-Orange Campus
    • Pomona, California, United States, 91767
      • Pomona Valley Hospital Medical Center
    • Stanford, California, United States, 94305
      • Stanford University Hospitals and Clinics
    • Sylmar, California, United States, 91342
      • Olive View-University of California Los Angeles Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80010
      • Colorado Gynecologic Oncology Group
    • Colorado Springs, Colorado, United States, 80909
      • Memorial Hospital Colorado Springs
    • Greeley, Colorado, United States, 80631
      • North Colorado Medical Center
    • Loveland, Colorado, United States, 80539
      • McKee Medical Center
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital
    • New Britain, Connecticut, United States, 06050
      • The Hospital of Central Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Beebe Medical Center
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Hospital Center
  • Florida
    • Fort Myers, Florida, United States, 33905
      • Florida Gynecologic Oncology
    • Jacksonville, Florida, United States, 32224-9980
      • Mayo Clinic in Florida
    • Orlando, Florida, United States, 32806
      • UF Cancer Center at Orlando Health
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Hospital
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital
    • Atlanta, Georgia, United States, 30342
      • Saint Joseph's Hospital of Atlanta
    • Augusta, Georgia, United States, 30912
      • Georgia Regents University
    • Columbus, Georgia, United States, 31904
      • John B Amos Cancer Center
    • Decatur, Georgia, United States, 30033
      • Dekalb Medical Center
    • Marietta, Georgia, United States, 30060
      • WellStar Kennestone Hospital
    • Savannah, Georgia, United States, 31403
      • Memorial Health University Medical Center
  • Hawaii
    • 'Aiea, Hawaii, United States, 96701
      • Pali Momi Medical Center
    • Honolulu, Hawaii, United States, 96813
      • Queen's Medical Center
    • Honolulu, Hawaii, United States, 96817
      • The Cancer Center of Hawaii-Liliha
    • Honolulu, Hawaii, United States, 96813
      • Straub Clinic and Hospital
    • Honolulu, Hawaii, United States, 96859
      • Tripler Army Medical Center
    • Honolulu, Hawaii, United States, 96813
      • University of Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Hawaii Minority Based CCOP
    • Wailuku, Hawaii, United States, 96793
      • Maui Memorial Medical Center
  • Illinois
    • Aurora, Illinois, United States, 60504
      • Rush - Copley Medical Center
    • Bloomington, Illinois, United States, 61701
      • Saint Joseph Medical Center
    • Canton, Illinois, United States, 61520
      • Graham Hospital Association
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Chicago, Illinois, United States, 60612
      • University of Illinois
    • Evanston, Illinois, United States, 60202
      • Saint Francis Hospital
    • Galesburg, Illinois, United States, 61401
      • Western Illinois Cancer Treatment Center
    • Joliet, Illinois, United States, 60435
      • Joliet Oncology-Hematology Associates Limited
    • Normal, Illinois, United States, 61761
      • Community Cancer Center Foundation
    • Normal, Illinois, United States, 61761
      • Bromenn Regional Medical Center
    • Park Ridge, Illinois, United States, 60068
      • Advocate Lutheran General Hospital.
    • Peoria, Illinois, United States, 61637
      • OSF Saint Francis Medical Center
    • Peoria, Illinois, United States, 61615
      • Illinois CancerCare-Peoria
    • Peru, Illinois, United States, 61354
      • Valley Radiation Oncology
    • Spring Valley, Illinois, United States, 61362
      • Saint Margaret's Hospital
    • Springfield, Illinois, United States, 62781-0001
      • Memorial Medical Center
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
    • Urbana, Illinois, United States, 61801
      • Carle Clinic-Urbana Main
  • Indiana
    • Elkhart, Indiana, United States, 46515
      • Elkhart General Hospital
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Medical Center
    • Indianapolis, Indiana, United States, 46237
      • Gynecologic Oncology of Indiana
    • Kokomo, Indiana, United States, 46904
      • Community Howard Regional Health
    • La Porte, Indiana, United States, 46350
      • IU Health La Porte Hospital
    • Michigan City, Indiana, United States, 46360
      • Franciscan Saint Anthony Health-Michigan City
    • Mishawaka, Indiana, United States, 46545-1470
      • Saint Joseph Regional Medical Center-Mishawaka
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
    • South Bend, Indiana, United States, 46628
      • Northern Indiana Cancer Research Consortium
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic PC-William R Bliss Cancer Center
    • Clive, Iowa, United States, 50325
      • Medical Oncology and Hematology Associates-West Des Moines
    • Des Moines, Iowa, United States, 50309
      • Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50309
      • Medical Oncology and Hematology Associates-Des Moines
    • Des Moines, Iowa, United States, 50316
      • Iowa Lutheran Hospital
    • Des Moines, Iowa, United States, 50314
      • Medical Oncology and Hematology Associates-Laurel
    • Des Moines, Iowa, United States, 50307
      • Mercy Capitol
    • Des Moines, Iowa, United States, 50309
      • Iowa Oncology Research Association CCOP
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
    • Sioux City, Iowa, United States, 51101
      • Siouxland Hematology Oncology Associates
  • Kansas
    • Anthony, Kansas, United States, 67003
      • Hospital District Sixth of Harper County
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas - Chanute
    • Dodge City, Kansas, United States, 67801
      • Cancer Center of Kansas - Dodge City
    • El Dorado, Kansas, United States, 67042
      • Cancer Center of Kansas - El Dorado
    • Fort Scott, Kansas, United States, 66701
      • Cancer Center of Kansas - Fort Scott
    • Independence, Kansas, United States, 67301
      • Cancer Center of Kansas-Independence
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
    • Kansas City, Kansas, United States, 66112
      • Providence Medical Center
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas-Kingman
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas - Newton
    • Overland Park, Kansas, United States, 66210
      • Radiation Oncology Practice Corporation Southwest
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas - Parsons
    • Pratt, Kansas, United States, 67124
      • Cancer Center of Kansas - Pratt
    • Salina, Kansas, United States, 67401
      • Cancer Center of Kansas - Salina
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas - Wellington
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas-Wichita Medical Arts Tower
    • Wichita, Kansas, United States, 67208
      • Associates In Womens Health
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas - Main Office
    • Wichita, Kansas, United States, 67214
      • Via Christi Regional Medical Center
    • Wichita, Kansas, United States, 67214
      • Wesley Medical Center
    • Wichita, Kansas, United States, 67214
      • Wichita CCOP
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas - Winfield
  • Kentucky
    • Edgewood, Kentucky, United States, 41017
      • Saint Elizabeth Medical Center South
    • Louisville, Kentucky, United States, 40202
      • The James Graham Brown Cancer Center at University of Louisville
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Health Sciences Center
    • Shreveport, Louisiana, United States, 71130
      • Louisiana State University Health Sciences Center Shreveport
  • Maine
    • Bangor, Maine, United States, 04401
      • Eastern Maine Medical Center
    • Portland, Maine, United States, 04102
      • Maine Medical Center-Bramhall Campus
  • Maryland
    • Elkton, Maryland, United States, 21921
      • Union Hospital of Cecil County
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Medical School
  • Michigan
    • Battle Creek, Michigan, United States, 49017
      • Bronson Battle Creek
    • Big Rapids, Michigan, United States, 49307
      • Spectrum Health Big Rapids Hospital
    • Detroit, Michigan, United States, 48201
      • Wayne State University/Karmanos Cancer Institute
    • Escanaba, Michigan, United States, 49431
      • Green Bay Oncology - Escanaba
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health at Butterworth Campus
    • Grand Rapids, Michigan, United States, 49503
      • Mercy Health Saint Mary's
    • Grand Rapids, Michigan, United States, 49503
      • Grand Rapids Clinical Oncology Program
    • Grand Rapids, Michigan, United States, 49506
      • Spectrum Health-Blodgett Campus
    • Grand Rapids, Michigan, United States, 49546
      • Gynecologic Oncology of West Michigan PLLC
    • Iron Mountain, Michigan, United States, 49801
      • Green Bay Oncology - Iron Mountain
    • Muskegon, Michigan, United States, 49444
      • Mercy Health Mercy Campus
    • Muskegon, Michigan, United States, 49442
      • Mercy Health Partners-Hackley Campus
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital-Royal Oak
    • Saint Joseph, Michigan, United States, 49085
      • Lakeland Hospital
    • Southfield, Michigan, United States, 48075
      • Providence Hospital
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
    • Wyoming, Michigan, United States, 49519
      • Metro Health Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
    • Shakopee, Minnesota, United States, 55379
      • Saint Francis Regional Medical Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri - Ellis Fischel
    • Independence, Missouri, United States, 64057
      • Centerpoint Medical Center LLC
    • Kansas City, Missouri, United States, 64114
      • Radiation Oncology Practice Corporation South
    • Kansas City, Missouri, United States, 64154
      • Radiation Oncology Practice Corporation - North
    • Saint Louis, Missouri, United States, 63110
      • Saint Louis University Hospital
    • Saint Louis, Missouri, United States, 63131
      • Missouri Baptist Medical Center
    • Saint Louis, Missouri, United States, 63141
      • Saint John's Mercy Medical Center
    • Saint Louis, Missouri, United States, 63141
      • Center for Cancer Care and Research
    • Springfield, Missouri, United States, 65807
      • CoxHealth South Hospital
    • Springfield, Missouri, United States, 65804
      • Mercy Hospital Springfield
    • Springfield, Missouri, United States, 65804
      • Ozark Health Ventures LLC-Cancer Research for The Ozarks Springfield
  • Montana
    • Billings, Montana, United States, 59101
      • Northern Rockies Radiation Oncology Center
    • Billings, Montana, United States, 59101
      • Montana Cancer Consortium CCOP
    • Billings, Montana, United States, 59102
      • Hematology-Oncology Centers of the Northern Rockies PC
    • Billings, Montana, United States, 59107-7000
      • Billings Clinic
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic
    • Great Falls, Montana, United States, 59405
      • Berdeaux, Donald MD (UIA Investigator)
  • Nebraska
    • Kearney, Nebraska, United States, 68847
      • Good Samaritan Hospital
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • Nevada
    • Reno, Nevada, United States, 89502
      • Renown Regional Medical Center
    • Reno, Nevada, United States, 89502
      • Center of Hope at Renown Medical Center
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital University Medical Center
    • Montclair, New Jersey, United States, 07042
      • Mountainside Hospital
    • Mount Holly, New Jersey, United States, 08060
      • Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County
    • Neptune, New Jersey, United States, 07753
      • Jersey Shore Medical Center
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
    • Newark, New Jersey, United States, 07103
      • UMDNJ - New Jersey Medical School
    • Toms River, New Jersey, United States, 08755
      • Community Medical Center
    • Voorhees, New Jersey, United States, 08043
      • Virtua West Jersey Hospital Voorhees
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico Cancer Center
  • New York
    • Albany, New York, United States, 12208
      • Women's Cancer Care Associates LLC
    • Brightwaters, New York, United States, 11718
      • Island Gynecologic Oncology
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center-Weiler Division
    • Brooklyn, New York, United States, 11203
      • State University of New York Downstate Medical Center
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • Jamaica, New York, United States, 11432
      • Queens Hospital Center
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital
    • Manhasset, New York, United States, 11030
      • North Shore-LIJ Health System CCOP
    • Middletown, New York, United States, 10940
      • Orange Regional Medical Center
    • New Hyde Park, New York, United States, 11040
      • Long Island Jewish Medical Center
    • New Hyde Park, New York, United States, 11040
      • North Shore-LIJ Health System/Center for Advanced Medicine
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10016
      • New York University Langone Medical Center
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
    • Syracuse, New York, United States, 13210
      • State University of New York Upstate Medical University
    • West Islip, New York, United States, 11795
      • Good Samaritan Hospital Medical Center
  • North Carolina
    • Asheville, North Carolina, United States, 28816
      • Hope Women's Cancer Centers-Asheville
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Wilmington, North Carolina, United States, 28401
      • New Hanover Regional Medical Center
    • Wilson, North Carolina, United States, 27893
      • Wilson Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Sanford Bismarck Medical Center
    • Bismarck, North Dakota, United States, 58501
      • Bismarck Cancer Center
    • Bismarck, North Dakota, United States, 58501
      • Mid Dakota Clinic
    • Bismarck, North Dakota, United States, 58501
      • Saint Alexius Medical Center
  • Ohio
    • Akron, Ohio, United States, 44307
      • Akron General Medical Center
    • Canton, Ohio, United States, 44710
      • Aultman Health Foundation
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cincinnati, Ohio, United States, 45220
      • Good Samaritan Hospital - Cincinnati
    • Cincinnati, Ohio, United States, 45242
      • Bethesda North Hospital
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic Cancer Center/Fairview Hospital
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital
    • Columbus, Ohio, United States, 43210
      • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
    • Columbus, Ohio, United States, 43222
      • Mount Carmel Health Center West
    • 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
    • Mayfield Heights, Ohio, United States, 44124
      • Hillcrest Hospital Cancer Center
    • Mentor, Ohio, United States, 44060
      • Lake University Ireland Cancer Center
    • Wright-Patterson Air Force Base, Ohio, United States, 45433-5529
      • Wright-Patterson Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
    • Tulsa, Oklahoma, United States, 74146
      • Tulsa Cancer Institute
    • Tulsa, Oklahoma, United States, 74104
      • Cancer Care Associates-Midtown
  • Oregon
    • Salem, Oregon, United States, 97301
      • Salem Hospital
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Memorial Hospital
    • Allentown, Pennsylvania, United States, 18105
      • Lehigh Valley Hospital
    • Bethlehem, Pennsylvania, United States, 18015
      • Saint Luke's University Hospital-Bethlehem Campus
    • Lancaster, Pennsylvania, United States, 17604
      • Lancaster General Hospital
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • Magee-Womens Hospital of UPMC
    • Pittsburgh, Pennsylvania, United States, 15224-1791
      • Western Pennsylvania Hospital
    • Scranton, Pennsylvania, United States, 18510
      • Scranton Hematology Oncology
    • Scranton, Pennsylvania, United States, 18501
      • Mercy Hospital
    • Scranton, Pennsylvania, United States, 18508
      • Hematology and Oncology Associates of North East Pennsylvania
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Women and Infants Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Black Hills Obstetrics and Gynecology
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Chattanooga's Program in Women's Oncology
    • Chattanooga, Tennessee, United States, 37403
      • Chattanooga Gynecological Oncology
    • Johnson City, Tennessee, United States, 37614-0054
      • East Tennessee State University
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt-Ingram Cancer Center
    • Nashville, Tennessee, United States, 37208-3599
      • Meharry Medical College
  • Texas
    • Amarillo, Texas, United States, 79106
      • The Don and Sybil Harrington Cancer Center
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Fort Sam Houston, Texas, United States, 78234
      • Brooke Army Medical Center
    • Galveston, Texas, United States, 77555-0565
      • University of Texas Medical Branch at Galveston
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center
    • Laredo, Texas, United States, 78041
      • Doctor's Hospital of Laredo
    • Lubbock, Texas, United States, 79430
      • Texas Tech University Health Sciences Center
  • Utah
    • American Fork, Utah, United States, 84003
      • American Fork Hospital
    • Logan, Utah, United States, 84321
      • Logan Regional Hospital
    • Murray, Utah, United States, 84107
      • Cottonwood Hospital Medical Center
    • Ogden, Utah, United States, 84403
      • McKay-Dee Hospital Center
    • Provo, Utah, United States, 84604-3337
      • Utah Valley Regional Medical Center
    • Saint George, Utah, United States, 84770
      • Dixie Medical Center Regional Cancer Center
    • 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
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Fletcher Allen Health Care-Medical Center
  • Virginia
    • Annandale, Virginia, United States, 22003
      • Northern Virginia Pelvic Surgery Associates
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
    • Newport News, Virginia, United States, 23602
      • Bon Secours Mary Immaculate Hospital
    • Norton, Virginia, United States, 24273
      • Southwest VA Regional Cancer Center
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
    • Roanoke, Virginia, United States, 24016
      • Carilion Clinic Gynecological Oncology
  • Washington
    • Puyallup, Washington, United States, 98372
      • Good Samaritan Community Hospital
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties PLLC
    • Tacoma, Washington, United States, 98405
      • Saint Joseph Medical Center
    • Tacoma, Washington, United States, 98415
      • MultiCare Health System
    • Tacoma, Washington, United States, 98405
      • Tacoma General Hospital
    • Tacoma, Washington, United States, 98405
      • Northwest CCOP
  • West Virginia
    • Wheeling, West Virginia, United States, 26003
      • Wheeling Hospital
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54301
      • Saint Vincent Hospital
    • Green Bay, Wisconsin, United States, 54303
      • Green Bay Oncology Limited at Saint Mary's Hospital
    • Green Bay, Wisconsin, United States, 54303
      • Saint Mary's Hospital
    • Green Bay, Wisconsin, United States, 54301-3526
      • Green Bay Oncology at Saint Vincent Hospital
    • Marinette, Wisconsin, United States, 54143
      • Bay Area Medical Center
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert and The Medical College of Wisconsin
    • Oconto Falls, Wisconsin, United States, 54154
      • Green Bay Oncology - Oconto Falls
    • Sturgeon Bay, Wisconsin, United States, 54235
      • Green Bay Oncology - Sturgeon Bay
    • West Allis, Wisconsin, United States, 53227
      • Aurora West Allis Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Histologically confirmed invasive squamous cell carcinoma, adenocarcinoma, or adenosquamous cell carcinoma of the uterine cervix

  • Stage IB2, IIA, IIB, IIIB, or IVA disease

    • Stage IIA tumors must be > 4 cm
  • Primary, untreated disease
• Negative, non-suspicious para-aortic nodes by lymphangiogram, CT scan, MRI, or lymphadenectomy
• Must have been adequately clinically staged
• Suitable for treatment with radical intent using concurrent chemotherapy and pelvic radiotherapy
• No disease involvement of the lower third of the vagina regardless of stage (all stage IIIA, IIIB and IVA with lower one-third involvement)
• No carcinoma of the cervical stump
• Performance status - GOG 0-3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• SGOT ≤ 3 times ULN
• Alkaline phosphatase ≤ 3 times ULN
• Creatinine ≤ ULN or calculated creatinine clearance ≥ 60mL/min
• No New York Heart Association class III-IV heart failure
• No history of myocardial infarction
• No unstable angina
• No uncontrolled hypertension
• No pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No septicemia or severe infection
• No other invasive malignancy within the past 5 years except nonmelanoma skin cancer
• No prior hysterectomy or planned hysterectomy as part of initial cervix cancer therapy
• No prior coronary artery bypass surgery
• No prior cancer therapy that would preclude study treatment
• No concurrent angina medication
• No concurrent intensity-modulated radiotherapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm I (cisplatin); Patients receive cisplatin IV on days 1, 8, 15, 22, 29, and 36 (weeks 1-6).	Drug: cisplatin; Given IV; Other Names: CDDP; DDP; CACP; CPDD
Experimental: Arm II (cisplatin, tirapazamine); Patients receive tirapazamine IV over 2 hours on days 1, 8, 10, 12, 15, 22, 24, 26, and 29 and cisplatin IV over 1 hour on days 1, 15, and 29.	Drug: cisplatin; Given IV; Other Names: CDDP; DDP; CACP; CPDD; Drug: tirapazamine; Given IV; Other Names: SR 4233; Tirazone; WIN 59075

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival - Percentage of Patients Alive and Progression Free	Patients' progression status based on clinical, radiological or pathological (histological) evidence of disease after study therapy. Progression includes any death without evidence of disease progression. Progression-free Survival (PFS) is defined as time in month from study enrollment to disease progression, death or date of last contact.	From study entry until first disease progression, death or date of last contact, up to 6 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	The observed length of life from entry into the study to death or date of last contact.	From study entry to death or last contact, up to 6 years
Adverse Events (Grade 3 or Higher) During Treatment Period	Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v3.0.	All Adverse Events (AEs) occuring during treatment and up to 30 days after stopping the study treatment are reported

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Collaborators: Gynecologic Oncology Group; NCIC Clinical Trials Group
• Investigators: Principal Investigator: Paul DiSilvestro, Gynecologic Oncology Group

Publications and helpful links

General Publications

• DiSilvestro PA, Ali S, Craighead PS, Lucci JA, Lee YC, Cohn DE, Spirtos NM, Tewari KS, Muller C, Gajewski WH, Steinhoff MM, Monk BJ. Phase III randomized trial of weekly cisplatin and irradiation versus cisplatin and tirapazamine and irradiation in stages IB2, IIA, IIB, IIIB, and IVA cervical carcinoma limited to the pelvis: a Gynecologic Oncology Group study. J Clin Oncol. 2014 Feb 10;32(5):458-64. doi: 10.1200/JCO.2013.51.4265. Epub 2014 Jan 6.

Study record dates

Study Major Dates

• Study Start: February 1, 2006
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: December 6, 2005
• First Submitted That Met QC Criteria: December 6, 2005
• First Posted (Estimate): December 7, 2005

Study Record Updates

• Last Update Posted (Actual): July 23, 2019
• Last Update Submitted That Met QC Criteria: July 19, 2019
• Last Verified: July 1, 2019

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; Uterine Cervical Neoplasms; Carcinoma; Carcinoma, Adenosquamous; Antineoplastic Agents; Tirapazamine
• Other Study ID Numbers: NCI-2009-00591 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA027469 (U.S. NIH Grant/Contract); CAN-NCIC-GOG-0219; CDR0000455555; GOG-0219 (Other Identifier: CTEP)