Chemotherapy and Pelvic Radiation Therapy With or Without Additional Chemotherapy in Treating Patients With High-Risk Early-Stage Cervical Cancer After Radical Hysterectomy

Sponsor

Radiation Therapy Oncology Group (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT00980954

Collaborator

National Cancer Institute (NCI) (NIH), NRG Oncology (Other)

238

Enrollment

125

Locations

Arms

203

Duration (Months)

1.9

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as cisplatin, paclitaxel, and carboplatin, 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. It is not yet known whether chemotherapy and radiation therapy are more effective when given with or without additional chemotherapy in treating cervical cancer.

PURPOSE: This randomized phase III trial is studying chemotherapy and pelvic radiation therapy to see how well they work when given with or without additional chemotherapy in treating patients with high-risk early-stage cervical cancer after radical hysterectomy.

Condition or Disease	Intervention/Treatment	Phase
Cervical Cancer	Drug: carboplatin Drug: cisplatin Drug: paclitaxel	Phase 3

Detailed Description

OBJECTIVES:

Primary

To determine if administering adjuvant systemic chemotherapy after chemoradiotherapy will improve disease-free survival compared to chemoradiotherapy alone in patients with high-risk early-stage cervical carcinoma found to have positive nodes and/or positive parametria after radical hysterectomy.

Secondary

To evaluate adverse events.
To evaluate overall survival.
To evaluate quality of life.
To evaluate chemotherapy-induced neuropathy.
To perform a post-hoc dose-volume evaluation between patients treated with standard radiotherapy and patients treated with intensity-modulated radiotherapy (IMRT) with respect to toxicity and local control.
To collect fixed tissue samples to identify tumor molecular signatures that may be associated with patient outcomes, such as adverse events, disease-free survival, and overall survival.
To collect blood samples to identify secreted factors from serum and plasma that may be associated with adverse events or outcome and to identify single nucleotide polymorphisms (SNPs) in genes from buffy coat that may be associated with a genetic predisposition to tumor formation itself or a response to cytotoxic therapy.

OUTLINE: This is a multicenter study. Patients are stratified according to planned use of brachytherapy (no vs. yes), radiotherapy modality - [standard external beam radiotherapy (EBRT) vs. intensity-modulated radiotherapy (IMRT)], and radiotherapy dose (45 Gy vs. 50.4 Gy). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients undergo standard EBRT or IMRT to the pelvis once daily 5 days a week for 5-6 weeks. Patients also receive concurrent cisplatin IV over 1 hour once weekly for 6 weeks.

NOTE: Some patients may also undergo brachytherapy beginning within 7 days after completion of radiotherapy.

Arm II: Patients receive chemoradiotherapy as in arm I. Beginning 4-6 weeks after completion of chemoradiotherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed by the Functional Assessment of Cancer Therapy - Gynecologic Oncology Group (FACT-GOG/NTX4), FACT-Cx, and FACIT-D questionnaires at baseline; at the completion of chemoradiotherapy; and then at 6, 12, and 24 months after completion of chemoradiotherapy.

Blood and tissue samples may be collected for gene expression analysis by immuno-histochemistry (IHC) and for biomarker and polymorphism studies.

After completion of study treatment, patients are followed up very 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Study Design

Study Type:

Interventional

Actual Enrollment :

238 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase III Randomized Study of Concurrent Chemotherapy and Pelvic Radiation Therapy With or Without Adjuvant Chemotherapy in High-Risk Patients With Early-Stage Cervical Carcinoma Following Radical Hysterectomy

Study Start Date :

Sep 1, 2009

Anticipated Primary Completion Date :

Aug 1, 2022

Anticipated Study Completion Date :

Aug 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I: Cisplatin/Radiation Therapy Patients undergo standard EBRT or IMRT to the pelvis once daily 5 days a week for 5-6 weeks. Patients also receive concurrent cisplatin IV over 1 hour once weekly for 6 weeks.	Drug: cisplatin Given IV
Experimental: Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel Patients receive chemoradiotherapy as in arm I. Beginning 4-6 weeks after completion of chemoradiotherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.	Drug: carboplatin Given IV Drug: cisplatin Given IV Drug: paclitaxel Given IV

Arm

Intervention/Treatment

Experimental: Arm I: Cisplatin/Radiation Therapy

Patients undergo standard EBRT or IMRT to the pelvis once daily 5 days a week for 5-6 weeks. Patients also receive concurrent cisplatin IV over 1 hour once weekly for 6 weeks.

Drug: cisplatin

Given IV

Experimental: Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel

Patients receive chemoradiotherapy as in arm I. Beginning 4-6 weeks after completion of chemoradiotherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Drug: carboplatin

Given IV

Drug: cisplatin

Given IV

Drug: paclitaxel

Given IV

Outcome Measures

Primary Outcome Measures

Disease-free survival [From randomization to date of first failure (local, regional, or distant metastases failure or death due to any cause) or last follow-up. Analysis occurs after 43 disease-free survival failure events on Cisplatin/RT Arm.]

Secondary Outcome Measures

Overall survival [From randomization to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 4 years.]
Chemotherapy-induced neuropathy as measured by FACT-GOG/NTX4 [From completion of concurrent chemoradiation to 12 months.]
Quality of life as measured by FACT-Cx and FACIT-D [From completion of concurrent chemoradiation to 12 months.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed squamous, adenosquamous, or adenocarcinoma of the cervix with any/all of the following high-risk features after surgery:
Positive pelvic nodes
Positive parametrium
Positive para-aortic nodes that have been completely resected and are PET/CT scan-negative
PET only required if positive para-aortic nodes during surgery
Clinical stage IA2, IB, or IIA disease (this corresponds to surgical tumor node metastasis (TNM) staging of T1-T2, N1, M0)
Must have undergone radical hysterectomy (open, laparoscopically, or robotic) and staging within the past 70 days
Para-aortic and pelvic node sampling required
If the patient did not have a para-aortic lymph node sampling/dissection, but had common iliac node dissection that was negative, a PET-CT is recommended, but not required
A negative pre- or post-operative PET scan or PET-CT scan of the para-aortic nodes is required if the patient did not undergo para-aortic or common iliac nodal sampling/dissection
No gross residual disease
No neuroendocrine histology
No distant metastases

PATIENT CHARACTERISTICS:

Zubrod performance status 0-1
Absolute neutrophil count (ANC) ≥ 1,800/mm³
Platelets ≥ 100,000/mm³
White blood cell count (WBC) ≥ 4,000/mm³
Hemoglobin ≥ 10.0 g/dL (transfusion or other intervention allowed)
Serum creatinine ≤ 1.5 mg/dL
Bilirubin ≤ 1.5 times upper limit of normal
Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) normal
Alkaline phosphatase normal
Known HIV positivity allowed provided cluster of differentiation 4 (CD4) count is ≥ 350/mm³ within the past 14 days
No other invasive malignancy within the past 3 years, except nonmelanomatous skin cancer or carcinoma in situ of the breast, oral cavity, or cervix
No severe, active co-morbidity, including any of the following:
Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
Transmural myocardial infarction within the past 6 months
Acute bacterial or fungal infection requiring IV antibiotics at the time of study entry
Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of study entry
Coagulation defects
No prior allergic reaction to carboplatin, paclitaxel, and/or cisplatin

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior systemic chemotherapy for the current cervical cancer
Prior chemotherapy for a different cancer is allowed
No prior radiotherapy to the pelvis that would result in overlap of radiotherapy fields

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Providence Hospital	Mobile	Alabama	United States	36608
3	Providence Alaska Medical Center	Anchorage	Alaska	United States	99508
4	Arizona Center for Cancer Care-Peoria	Peoria	Arizona	United States	85381
5	Saint Joseph's Hospital and Medical Center	Phoenix	Arizona	United States	85013
6	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California	United States	91505
7	Mercy San Juan Medical Center	Carmichael	California	United States	95608
8	City of Hope Medical Center	Duarte	California	United States	91010
9	Saint Joseph Hospital - Orange	Orange	California	United States	92868
10	Pomona Valley Hospital Medical Center	Pomona	California	United States	91767
11	Mercy Cancer Center	Sacramento	California	United States	95816
12	Mercy General Hospital Radiation Oncology Center	Sacramento	California	United States	95819
13	Saint Helena Hospital	Saint Helena	California	United States	94574
14	University of California At San Diego	San Diego	California	United States	92103
15	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado	United States	80907
16	Hartford Hospital	Hartford	Connecticut	United States	06102
17	The Hospital of Central Connecticut	New Britain	Connecticut	United States	06050
18	University of Miami Sylvester Comprehensive Cancer Center at Deerfield Beach	Deerfield Beach	Florida	United States	33442
19	Memorial Healthcare System - Joe DiMaggio Children's Hospital	Hollywood	Florida	United States	33021
20	Jackson Memorial Hospital-Holtz Children's Hospital	Miami	Florida	United States	33136
21	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida	United States	33136
22	Baptist Hospital of Miami	Miami	Florida	United States	33176
23	Florida Hospital	Orlando	Florida	United States	32803
24	Grady Health System	Atlanta	Georgia	United States	30303
25	Northside Hospital	Atlanta	Georgia	United States	30342
26	Northeast Georgia Medical Center	Gainesville	Georgia	United States	30501
27	Memorial Health University Medical Center	Savannah	Georgia	United States	31403
28	Saint Joseph's-Candler Health System	Savannah	Georgia	United States	31405
29	Queen's Medical Center	Honolulu	Hawaii	United States	96813
30	University of Hawaii	Honolulu	Hawaii	United States	96813
31	Saint Alphonsus Regional Medical Center	Boise	Idaho	United States	83706
32	Northwestern University	Chicago	Illinois	United States	60611
33	Rush University Medical Center	Chicago	Illinois	United States	60612
34	OSF Saint Francis Medical Center	Peoria	Illinois	United States	61637
35	Saint Vincent Anderson Regional Hospital/Cancer Center	Anderson	Indiana	United States	46016
36	Saint Francis Hospital and Health Centers	Beech Grove	Indiana	United States	46107
37	Franciscan Saint Margaret Health-Hammond Campus	Hammond	Indiana	United States	46320
38	Franciscan Saint Francis Health-Indianapolis	Indianapolis	Indiana	United States	46237
39	Michiana Hematology Oncology PC-Mishawaka	Mishawaka	Indiana	United States	46545-1470
40	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
41	Mercy Medical Center - North Iowa	Mason City	Iowa	United States	50401
42	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
43	Kansas City Cancer Centers-Southwest	Overland Park	Kansas	United States	66210
44	Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
45	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
46	Greater Baltimore Medical Center	Baltimore	Maryland	United States	21204
47	Sinai Hospital of Baltimore	Baltimore	Maryland	United States	21215
48	Central Maryland Radiation Oncology in Howard County	Columbia	Maryland	United States	21044
49	Holy Cross Hospital	Silver Spring	Maryland	United States	20910
50	Hickman Cancer Center	Adrian	Michigan	United States	49221
51	Saint John Hospital and Medical Center	Detroit	Michigan	United States	48236
52	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
53	Saint Joseph Mercy Port Huron	Port Huron	Michigan	United States	48060
54	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
55	Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55407
56	Mayo Clinic	Rochester	Minnesota	United States	55905
57	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
58	Kansas City Cancer Center - South	Kansas City	Missouri	United States	64131
59	Kansas City Cancer Centers - North	Kansas City	Missouri	United States	64154
60	Kansas City Cancer Center-Lee's Summit	Lee's Summit	Missouri	United States	64064
61	Phelps County Regional Medical Center	Rolla	Missouri	United States	65401
62	Saint John's Mercy Medical Center	Saint Louis	Missouri	United States	63141
63	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
64	CoxHealth South Hospital	Springfield	Missouri	United States	65807
65	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
66	The Nebraska Medical Center	Omaha	Nebraska	United States	68198
67	Elliot Hospital	Manchester	New Hampshire	United States	03103
68	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
69	Morristown Memorial Hospital	Morristown	New Jersey	United States	07962
70	Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County	Mount Holly	New Jersey	United States	08060
71	UMDNJ - New Jersey Medical School	Newark	New Jersey	United States	07103
72	MD Anderson Cancer Center at Cooper-Voorhees	Voorhees	New Jersey	United States	08043
73	Montefiore Medical Center-Weiler Division	Bronx	New York	United States	10461
74	Montefiore Medical Center	Bronx	New York	United States	10467-2490
75	State University of New York Downstate Medical Center	Brooklyn	New York	United States	11203
76	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
77	Highland Hospital	Rochester	New York	United States	14620
78	University of Rochester	Rochester	New York	United States	14642
79	Carolinas Medical Center	Charlotte	North Carolina	United States	28203
80	Summa Akron City Hospital/Cooper Cancer Center	Akron	Ohio	United States	44304
81	Akron General Medical Center	Akron	Ohio	United States	44307
82	Summa Barberton Hospital	Barberton	Ohio	United States	44203
83	University of Cincinnati	Cincinnati	Ohio	United States	45267
84	Case Western Reserve University	Cleveland	Ohio	United States	44106
85	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center	Columbus	Ohio	United States	43210
86	Summa Health Center at Lake Medina	Medina	Ohio	United States	44256
87	UHHS-Chagrin Highlands Medical Center	Orange Village	Ohio	United States	44122
88	Southern Ohio Medical Center	Portsmouth	Ohio	United States	45662
89	Robinson Radiation Oncology	Ravenna	Ohio	United States	44266
90	Cancer Care Center, Incorporated	Salem	Ohio	United States	44460
91	Ireland Cancer Center at Firelands Regional Medical Center	Sandusky	Ohio	United States	44870
92	Flower Hospital	Sylvania	Ohio	United States	43560
93	University of Toledo	Toledo	Ohio	United States	43614
94	UHHS-Westlake Medical Center	Westlake	Ohio	United States	44145
95	Cancer Treatment Center	Wooster	Ohio	United States	44691
96	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
97	Providence Portland Medical Center	Portland	Oregon	United States	97213
98	Providence Saint Vincent Medical Center	Portland	Oregon	United States	97225
99	Delaware County Memorial Hospital	Drexel Hill	Pennsylvania	United States	19026
100	Reading Hospital	West Reading	Pennsylvania	United States	19611
101	Lankenau Hospital	Wynnewood	Pennsylvania	United States	19096
102	Women and Infants Hospital	Providence	Rhode Island	United States	02905
103	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
104	Sanford Cancer Center-Oncology Clinic	Sioux Falls	South Dakota	United States	57104
105	University of Tennessee - Knoxville	Knoxville	Tennessee	United States	37920
106	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
107	M D Anderson Cancer Center	Houston	Texas	United States	77030
108	Methodist Hospital	Houston	Texas	United States	77030
109	Intermountain Medical Center	Murray	Utah	United States	84157
110	McKay-Dee Hospital Center	Ogden	Utah	United States	84403
111	Dixie Medical Center Regional Cancer Center	Saint George	Utah	United States	84770
112	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah	United States	84112
113	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
114	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington	United States	98902
115	Wheeling Hospital	Wheeling	West Virginia	United States	26003
116	Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301
117	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin	United States	53215
118	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
119	Aurora West Allis Medical Center	West Allis	Wisconsin	United States	53227
120	McGill University Department of Oncology	Montreal	Quebec	Canada	H2W 1S6
121	Pamela Youde Nethersole Eastern Hospital	Chai Wan		Hong Kong
122	Seoul National University Bundang Hospital	Seongnam City	Kyeonggi-do	Korea, Republic of	463-707
123	Seoul National University Hospital	Seoul		Korea, Republic of	110-744
124	Gangnam Severance Hospital	Seoul		Korea, Republic of	135-720
125	Korea Cancer Center Hospital	Seoul		Korea, Republic of	139-706