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

Sponsor

Gynecologic Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00003078

Collaborator

National Cancer Institute (NCI) (NIH)

870

Enrollment

Locations

13.2

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cervical Cancer	Drug: cisplatin Drug: fluorouracil Radiation: brachytherapy Radiation: radiation therapy	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

870 participants

Allocation:

Randomized

Primary Purpose:

Treatment

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 Start Date :

Oct 1, 1997

Actual Primary Completion Date :

Nov 1, 2005

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama Comprehensive Cancer Center	Birmingham	Alabama	United States	35294
2	CCOP - Greater Phoenix	Phoenix	Arizona	United States	85006-2726
3	USC/Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033-0800
4	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California	United States	90095-1781
5	Chao Family Comprehensive Cancer Center	Orange	California	United States	92868
6	Women's Cancer Center	Palo Alto	California	United States	94304
7	University of Colorado Cancer Center	Denver	Colorado	United States	80262
8	Vincent T. Lombardi Cancer Research Center, Georgetown University	Washington	District of Columbia	United States	20007
9	Walter Reed Army Medical Center	Washington	District of Columbia	United States	20307-5000
10	Fred J. Woods Radiation Therapy Center/St. Joseph's Cancer Institute	Tampa	Florida	United States	33607
11	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612
12	Emory University Hospital - Atlanta	Atlanta	Georgia	United States	30322
13	MBCCOP - Hawaii	Honolulu	Hawaii	United States	96813
14	Rush-Presbyterian-St. Luke's Medical Center	Chicago	Illinois	United States	60612
15	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637
16	CCOP - Central Illinois	Decatur	Illinois	United States	62526
17	CCOP - Evanston	Evanston	Illinois	United States	60201
18	Indiana University Cancer Center	Indianapolis	Indiana	United States	46202-5265
19	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
20	Albert B. Chandler Medical Center, University of Kentucky	Lexington	Kentucky	United States	40536-0084
21	Johns Hopkins Oncology Center	Baltimore	Maryland	United States	21287
22	Medicine Branch	Bethesda	Maryland	United States	20892
23	Radiation Oncology Branch	Bethesda	Maryland	United States	20892
24	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts	United States	01655
25	CCOP - Ann Arbor Regional	Ann Arbor	Michigan	United States	48106
26	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201
27	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216-4505
28	CCOP - Kansas City	Kansas City	Missouri	United States	64131
29	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
30	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
31	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68131
32	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
33	Cooper Hospital/University Medical Center	Camden	New Jersey	United States	08103
34	Cancer Center of Albany Medical Center	Albany	New York	United States	12208
35	State University of New York Health Science Center at Brooklyn	Brooklyn	New York	United States	11203
36	North Shore University Hospital	Manhasset	New York	United States	11030
37	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
38	University of Rochester Cancer Center	Rochester	New York	United States	14642
39	State University of New York Health Sciences Center - Stony Brook	Stony Brook	New York	United States	11790-9832
40	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina	United States	27599-7295
41	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
42	Comprehensive Cancer Center of Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina	United States	27157-1082
43	Barrett Cancer Center, The University Hospital	Cincinnati	Ohio	United States	45219
44	Ireland Cancer Center	Cleveland	Ohio	United States	44106-5065
45	Cleveland Clinic Cancer Center	Cleveland	Ohio	United States	44195
46	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio	United States	43210
47	University of Oklahoma College of Medicine	Oklahoma City	Oklahoma	United States	73190
48	CCOP - Sooner State	Tulsa	Oklahoma	United States	74136
49	CCOP - Columbia River Program	Portland	Oregon	United States	97213
50	Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
51	Delaware County Memorial Hospital	Drexel Hill	Pennsylvania	United States	19026
52	Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033
53	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania	United States	19104
54	Kimmel Cancer Center of Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania	United States	19107
55	Pennsylvania Hospital	Philadelphia	Pennsylvania	United States	19107
56	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
57	Medical University of South Carolina	Charleston	South Carolina	United States	29425-0721
58	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
59	CCOP - Baptist Cancer Institute	Memphis	Tennessee	United States	38117
60	Brookview Research, Inc.	Nashville	Tennessee	United States	37203
61	Simmons Cancer Center - Dallas	Dallas	Texas	United States	75235-9154
62	University of Texas - MD Anderson Cancer Center	Houston	Texas	United States	77030
63	Cancer Center, University of Virginia HSC	Charlottesville	Virginia	United States	22908
64	University of Washington Medical Center	Seattle	Washington	United States	98195-6043
65	Tacoma General Hospital	Tacoma	Washington	United States	98405
66	NCIC-Clinical Trials Group	Kingston	Ontario	Canada	K7L 3N6