Clinical trial NCT00003078: Radiation Therapy With or Without Cisplatin or Fluorouracil in Treating Patients With Cancer of the Cervix
Official title: A Randomized Comparison of Radiation vs Radiation Plus Weekly Cisplatin vs Radiation Plus PVI (Protracted Venous Infusion) 5-FU in Patients With Stage II-B, III-B, and IV-A Carcinoma of the Cervix With Negative Paraaortic Nodes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cervical Cancer
Keywords: stage III cervical cancer
stage IIB cervical cancer
stage IVA cervical cancer
cervical squamous cell carcinoma
cervical adenocarcinoma
cervical adenosquamous cell carcinoma
Lead sponsor: GOG Foundation
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-06-23
Enrollment: 870
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy and chemotherapy may kill more tumor cells. It is not known whether receiving radiation therapy plus cisplatin is more effective than receiving radiation therapy plus fluorouracil in treating patients with cancer of the cervix.

PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy plus cisplatin or fluorouracil in treating patients with primary stage IIB, stage IIIB, or stage IVA cancer of the cervix.

Detailed description: OBJECTIVES: I. Compare the progression-free survival and survival of patients with advanced cervical cancer limited to the pelvis receiving either radiotherapy alone, or radiotherapy plus weekly cisplatin, or radiotherapy plus prolonged venous infusion (PVI) of fluorouracil. \[Radiotherapy alone regimen closed 8/18/98\] II. Determine the relative toxic effects of radiation therapy plus chemotherapy with either weekly cisplatin or PVI fluorouracil compared to radiation alone. \[Radiotherapy alone regimen closed 8/18/98\] IV. Compare the progression-free survival and survival of patients with advanced cervical cancer limited to the pelvis and who smoke at the time of diagnosis versus non-smokers and those who smoke during radiation therapy versus those who quit.

OUTLINE: This is a randomized study. Patients are stratified by stage, performance of para-aortic lymphadenectomy, and brachytherapy method (HDR vs LDR). Prior to treatment patients complete a questionnaire regarding past and present smoking history and exposure to secondhand smoke. In arm I, patients undergo external radiation therapy to the pelvis once daily 5 times a week for 5 weeks. Then, patients receive either low dose rate or high dose rate intracavitary brachytherapy in one or two applications or 5 fractions once or twice a week, respectively. If intracavitary radiation therapy cannot be performed, then shrinking field technique is executed. In addition, patients receive parametrial boost once daily for 3 to 5 days during intracavitary brachytherapy. Concurrently, patients receive IV cisplatin once a week for 5 weeks beginning on day 1 of external radiation therapy and once during the parametrial boost. Patients in arm II receive external radiation therapy and brachytherapy as previously described. \[Arm II closed 8/18/98\] In arm III, patients undergo external radiation therapy as described in arm I. In addition, patients receive prolonged venous infusion (PVI) fluorouracil daily for 5 days during external beam radiation therapy (whole pelvis and parametrial boost). If all 6 courses of cisplatin or fluorouracil cannot be administered during external radiation therapy, then the sixth course of chemotherapy will be given during brachytherapy. Patients are followed every 3 months for the first 2 years, then every 6 months for the next 3 years, then annually until death.

PROJECTED ACCRUAL: This study will accrue a maximum of 870 patients over 66 months.

Eligibility criteria: DISEASE CHARACTERISTICS: Primary, previously untreated, histologically confirmed invasive squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix stage IIB, IIIB, or IVA Negative para-aortic lymph nodes determined by lymphangiogram, CT, MRI, or lymphadenectomy (excluding suspicious para-aortic lymph nodes) Para-aortic lymphadenectomy must be performed extraperitoneally or by laparoscopy No histologically confirmed cancer involving the para-aortic lymph nodes, intraperitoneal disease, or positive peritoneal cytology No recurrent invasive carcinoma of the uterine cervix, regardless of previous treatment or cervix cancers other than squamous cell, adenosquamous, or adenocarcinoma No carcinoma of the cervical stump

PATIENT CHARACTERISTICS: Age: Any age Performance status: GOG 0-3 Life expectancy: Not specified Hematopoietic: WBC at least 3,000/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 times normal SGOT and alkaline phosphatase no greater than 3 times normal Renal: Creatinine no greater than 2.0 mg/dL Other: No septicemia or severe infection Not pregnant Negative pregnancy test Effective contraception required of fertile patients No other invasive malignancy unless disease free for at least 5 years and no prior cancer treatment that contraindicated this protocol therapy No concomitant malignancy other than nonmelanomatous skin cancer Must complete smoking history questionnaire and provide urine specimen for cotinine analysis

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior cytotoxic chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior radiation therapy to the pelvis Surgery: No prior hysterectomy

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Comprehensive Cancer Center
state: Alabama
city: Phoenix
country: United States
facility: CCOP - Greater Phoenix
state: Arizona
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center, UCLA
state: California
city: Orange
country: United States
facility: Chao Family Comprehensive Cancer Center
state: California
city: Palo Alto
country: United States
facility: Women's Cancer Center
state: California
city: Denver
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Washington
country: United States
facility: Vincent T. Lombardi Cancer Research Center, Georgetown University
state: District of Columbia
city: Washington
country: United States
facility: Walter Reed Army Medical Center
state: District of Columbia
city: Tampa
country: United States
facility: Fred J. Woods Radiation Therapy Center/St. Joseph's Cancer Institute
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital - Atlanta
state: Georgia
city: Honolulu
country: United States
facility: MBCCOP - Hawaii
state: Hawaii
city: Chicago
country: United States
facility: Rush-Presbyterian-St. Luke's Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Decatur
country: United States
facility: CCOP - Central Illinois
state: Illinois
city: Evanston
country: United States
facility: CCOP - Evanston
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Lexington
country: United States
facility: Albert B. Chandler Medical Center, University of Kentucky
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Oncology Center
state: Maryland
city: Bethesda
country: United States
facility: Medicine Branch
state: Maryland
city: Bethesda
country: United States
facility: Radiation Oncology Branch
state: Maryland
city: Worcester
country: United States
facility: University of Massachusetts Memorial Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: CCOP - Ann Arbor Regional
state: Michigan
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: CCOP - Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Billings
country: United States
facility: CCOP - Montana Cancer Consortium
state: Montana
city: Omaha
country: United States
facility: CCOP - Missouri Valley Cancer Consortium
state: Nebraska
city: Las Vegas
country: United States
facility: CCOP - Southern Nevada Cancer Research Foundation
state: Nevada
city: Camden
country: United States
facility: Cooper Hospital/University Medical Center
state: New Jersey
city: Albany
country: United States
facility: Cancer Center of Albany Medical Center
state: New York
city: Brooklyn
country: United States
facility: State University of New York Health Science Center at Brooklyn
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Cancer Center
state: New York
city: Stony Brook
country: United States
facility: State University of New York Health Sciences Center - Stony Brook
state: New York
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center, UNC
state: North Carolina
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center of Wake Forest University Baptist Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Barrett Cancer Center, The University Hospital
state: Ohio
city: Cleveland
country: United States
facility: Ireland Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital - Ohio State University
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma College of Medicine
state: Oklahoma
city: Tulsa
country: United States
facility: CCOP - Sooner State
state: Oklahoma
city: Portland
country: United States
facility: CCOP - Columbia River Program
state: Oregon
city: Abington
country: United States
facility: Abington Memorial Hospital
state: Pennsylvania
city: Drexel Hill
country: United States
facility: Delaware County Memorial Hospital
state: Pennsylvania
city: Hershey
country: United States
facility: Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Kimmel Cancer Center of Thomas Jefferson University - Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Pennsylvania Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Spartanburg
country: United States
facility: CCOP - Upstate Carolina
state: South Carolina
city: Memphis
country: United States
facility: CCOP - Baptist Cancer Institute
state: Tennessee
city: Nashville
country: United States
facility: Brookview Research, Inc.
state: Tennessee
city: Dallas
country: United States
facility: Simmons Cancer Center - Dallas
state: Texas
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
city: Charlottesville
country: United States
facility: Cancer Center, University of Virginia HSC
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Tacoma
country: United States
facility: Tacoma General Hospital
state: Washington
city: Kingston
country: Canada
facility: NCIC-Clinical Trials Group
state: Ontario
Study officials:
affiliation: Delaware County Regional Cancer Center at Delaware County Memorial Hospital
name: Rachelle M. Lanciano, MD
role: STUDY_CHAIR
References:
citation: Rose PG, Ali S, Whitney CW, Lanciano R, Stehman FB. Outcome of stage IVA cervical cancer patients with disease limited to the pelvis in the era of chemoradiation: a Gynecologic Oncology Group study. Gynecol Oncol. 2011 Jun 1;121(3):542-5. doi: 10.1016/j.ygyno.2011.02.024. Epub 2011 Mar 21.
citation: Rose PG, Ali S, Whitney CW, Lanciano R, Stehman FB. Impact of hydronephrosis on outcome of stage IIIB cervical cancer patients with disease limited to the pelvis, treated with radiation and concurrent chemotherapy: a Gynecologic Oncology Group study. Gynecol Oncol. 2010 May;117(2):270-5. doi: 10.1016/j.ygyno.2010.01.045. Epub 2010 Feb 24.
citation: Kunos C, Tian C, Waggoner S, Rose PG, Lanciano R. Retrospective analysis of concomitant Cisplatin during radiation in patients aged 55 years or older for treatment of advanced cervical cancer: a gynecologic oncology group study. Int J Gynecol Cancer. 2009 Oct;19(7):1258-63. doi: 10.1111/IGC.0b013e3181b33ace.
citation: Gold MA, Tian C, Whitney CW, Rose PG, Lanciano R. Surgical versus radiographic determination of para-aortic lymph node metastases before chemoradiation for locally advanced cervical carcinoma: a Gynecologic Oncology Group Study. Cancer. 2008 May 1;112(9):1954-63. doi: 10.1002/cncr.23400.
citation: Monk BJ, Tian C, Rose PG, Lanciano R. Which clinical/pathologic factors matter in the era of chemoradiation as treatment for locally advanced cervical carcinoma? Analysis of two Gynecologic Oncology Group (GOG) trials. Gynecol Oncol. 2007 May;105(2):427-33. doi: 10.1016/j.ygyno.2006.12.027. Epub 2007 Feb 2.
citation: Gold M, Tian C, Whitney CW, et al.: Surgical versus radiologic exclusion of para-aortic lymph node metastases relative to chemoradiation for loco-regionally advanced cervical carcinoma: a meta-analysis of Gynecologic Oncology Group (GOG) protocols 85, 120 & 165. [Abstract] Society of Gynecologic Oncologists, 2006 Annual Meeting on Women's Cancer, March 22-26, 2006, Palm Springs, CA. A-39, 2006.
citation: Waggoner SE, Darcy KM, Tian C, Lanciano R. Smoking behavior in women with locally advanced cervical carcinoma: a Gynecologic Oncology Group study. Am J Obstet Gynecol. 2010 Mar;202(3):283.e1-7. doi: 10.1016/j.ajog.2009.10.884. Epub 2009 Dec 30.
citation: Waggoner SE, Darcy KM, Fuhrman B, Parham G, Lucci J 3rd, Monk BJ, Moore DH; Gynecologic Oncology Group. Association between cigarette smoking and prognosis in locally advanced cervical carcinoma treated with chemoradiation: a Gynecologic Oncology Group study. Gynecol Oncol. 2006 Dec;103(3):853-8. doi: 10.1016/j.ygyno.2006.05.017. Epub 2006 Jul 3.
citation: Lanciano R, Calkins A, Bundy BN, Parham G, Lucci JA 3rd, Moore DH, Monk BJ, O'Connor DM. Randomized comparison of weekly cisplatin or protracted venous infusion of fluorouracil in combination with pelvic radiation in advanced cervix cancer: a gynecologic oncology group study. J Clin Oncol. 2005 Nov 20;23(33):8289-95. doi: 10.1200/JCO.2004.00.0497. Epub 2005 Oct 17.
citation: Varia MA, Bundy BN, Deppe G, Mannel R, Averette HE, Rose PG, Connelly P. Cervical carcinoma metastatic to para-aortic nodes: extended field radiation therapy with concomitant 5-fluorouracil and cisplatin chemotherapy: a Gynecologic Oncology Group study. Int J Radiat Oncol Biol Phys. 1998 Dec 1;42(5):1015-23. doi: 10.1016/s0360-3016(98)00267-3.