Radiation Therapy With or Without Cisplatin or Fluorouracil in Treating Patients With Cancer of the Cervix

Cervical Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003078
• Other study ID #: CDR0000065771
• Secondary ID: GOG-0165
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: July 8, 2013
• Start date: October 1997

Study information

• Verified date: April 2011
• Source: Gynecologic Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 870
• Est. primary completion date: November 2005
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cervical Cancer
• Uterine Cervical Neoplasms

Intervention

Drug:
• cisplatin

• fluorouracil

Radiation:
• brachytherapy

• radiation therapy

Locations

Country	Name	City	State
Canada	NCIC-Clinical Trials Group	Kingston	Ontario
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	Cancer Center of Albany Medical Center	Albany	New York
United States	CCOP - Ann Arbor Regional	Ann Arbor	Michigan
United States	Emory University Hospital - Atlanta	Atlanta	Georgia
United States	Johns Hopkins Oncology Center	Baltimore	Maryland
United States	Medicine Branch	Bethesda	Maryland
United States	Radiation Oncology Branch	Bethesda	Maryland
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	University of Alabama Comprehensive Cancer Center	Birmingham	Alabama
United States	State University of New York Health Science Center at Brooklyn	Brooklyn	New York
United States	Cooper Hospital/University Medical Center	Camden	New Jersey
United States	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Cancer Center, University of Virginia HSC	Charlottesville	Virginia
United States	Rush-Presbyterian-St. Luke's Medical Center	Chicago	Illinois
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Barrett Cancer Center, The University Hospital	Cincinnati	Ohio
United States	Cleveland Clinic Cancer Center	Cleveland	Ohio
United States	Ireland Cancer Center	Cleveland	Ohio
United States	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio
United States	Simmons Cancer Center - Dallas	Dallas	Texas
United States	CCOP - Central Illinois	Decatur	Illinois
United States	University of Colorado Cancer Center	Denver	Colorado
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Delaware County Memorial Hospital	Drexel Hill	Pennsylvania
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	CCOP - Evanston	Evanston	Illinois
United States	Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	MBCCOP - Hawaii	Honolulu	Hawaii
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	CCOP - Kansas City	Kansas City	Missouri
United States	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Albert B. Chandler Medical Center, University of Kentucky	Lexington	Kentucky
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center	Los Angeles	California
United States	North Shore University Hospital	Manhasset	New York
United States	CCOP - Baptist Cancer Institute	Memphis	Tennessee
United States	Brookview Research, Inc.	Nashville	Tennessee
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	University of Oklahoma College of Medicine	Oklahoma City	Oklahoma
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Chao Family Comprehensive Cancer Center	Orange	California
United States	Women's Cancer Center	Palo Alto	California
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Kimmel Cancer Center of Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania
United States	CCOP - Greater Phoenix	Phoenix	Arizona
United States	CCOP - Columbia River Program	Portland	Oregon
United States	University of Rochester Cancer Center	Rochester	New York
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of Washington Medical Center	Seattle	Washington
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	State University of New York Health Sciences Center - Stony Brook	Stony Brook	New York
United States	Tacoma General Hospital	Tacoma	Washington
United States	Fred J. Woods Radiation Therapy Center/St. Joseph's Cancer Institute	Tampa	Florida
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	CCOP - Sooner State	Tulsa	Oklahoma
United States	Vincent T. Lombardi Cancer Research Center, Georgetown University	Washington	District of Columbia
United States	Walter Reed Army Medical Center	Washington	District of Columbia
United States	Comprehensive Cancer Center of Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina
United States	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Gynecologic Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (10)

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.

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. — View 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. — View 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 — View 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. Epub 2007 Feb 2. — View 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. — View 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. — View 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. I — View 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 st — View 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. — View Citation