Intensity-Modulated Radiation Therapy to the Pelvis With or Without Chemotherapy in Treating Patients With Endometrial Cancer or Cervical Cancer That Has Been Removed By Surgery

• Sponsor: Radiation Therapy Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00331760
• Collaborator: National Cancer Institute (NCI) (NIH), NRG Oncology (Other)
• Enrollment: 106
• Locations: 153
• Arms: 2
• Duration (Months): 129.1
• Patients Per Site: 0.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Specialized radiation therapy (RT), such as intensity-modulated radiation therapy (IMRT), that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving intensity-modulated radiation therapy to the pelvis with or without chemotherapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying how well intensity-modulated radiation therapy to the pelvis with or without chemotherapy works in treating patients with endometrial cancer or cervical cancer that has been removed by surgery.

Condition or Disease	Intervention/Treatment	Phase
Cervical Cancer; Endometrial Cancer	Drug: cisplatin; Radiation: intensity-modulated radiation therapy	Phase 2

Detailed Description

OBJECTIVES:

• Determine the transportability of intensity modulated radiotherapy (IMRT) to a multi-institutional setting in patients with resected endometrial or cervical cancer.

• Compare the efficacy, in terms of reducing short-term bowel injury, of IMRT versus standard treatments.

• Assess adverse events related to this regimen.

• Estimate the rates of local-regional control, distant metastasis, and disease-free and overall survival.

• Evaluate chemotherapy compliance with this regimen for patients with cervical carcinoma.

OUTLINE: This is a multicenter study. Patients are stratified according to diagnosis (cervical vs endometrial cancer).

All patients undergo intensity modulated radiotherapy (IMRT) once a day, 5 days a week, for 5.5 weeks. Patients with cervical cancer also receive cisplatin IV over 30-60 minutes on day 1 or 2. Treatment with cisplatin repeats every 7 days for 5 courses (during radiotherapy) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 6 weeks post-IMRT and then every 3 months for 2 years, every 6 months for years 3-5, and then annually for at least 3 years.

PROJECTED ACCRUAL: A total of 92 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 106 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Intensity Modulated Radiation Therapy (IMRT) to the Pelvis ± Chemotherapy for Post-Operative Patients With Either Endometrial or Cervical Carcinoma
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Feb 1, 2009
• Actual Study Completion Date: Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Other: Endometrial Cancer: IMRT Endometrial Cancer patients receive Intensity Modulated Radiation Therapy (IMRT) 28 fractions over 5.5 weeks.	Radiation: intensity-modulated radiation therapy
Other: Cervical Cancer: IMRT + Chemotherapy (cisplatin) Cervical patients receive Intensity Modulated Radiation Therapy (IMRT) 28 fractions over 5.5 weeks and concurrent weekly cisplatin 40 mg/m^2 for five weeks.	Drug: cisplatin; Radiation: intensity-modulated radiation therapy

Outcome Measures

Primary Outcome Measures

1. Reproducibility of Radiation Technique (Number of Unacceptable Deviations in Central IMRT Quality Assurance Review) [IMRT planning and dosing data is centrally reviewed for quality assurance after treatment delivery.]

   Central quality assurance review of the IMRT planning and dosing categorized unacceptable deviations (UD) from protocol compliance with the delineation of planning target volume for the vagina and pelvic lymph nodes. Each arm of this study is considered independently, they are not compared to each other. The study was designed such that, for each arm, 5 or more of 42 subjects scored as unacceptable would determine the respective treatment technique as not reproducible. For each arm this design provides 90% power with a 0.05 type I error to reject the null hypothesis that the true probability of concluding the given technique to be reproducible is <= 80%. The alternative hypothesis is that the true probability is >= 95%. For [vagina / pelvic lymph nodes]: UD is defined as: The 90% isodose surface covers < 95% of [internal target volume (ITV)/ planned target volume (PTV)] 50.4 or > 5% of the [ITV/PTV] 50.4 receives over 115%.

Secondary Outcome Measures

1. Percentage of Patients With Grade 2+ Bowel Adverse Events [From the start of treatment to 90 days.]

   Bowel adverse events are defined as any of the following adverse events: diarrhea; enteritis; fistula; ileus:gastrointestinal (GI); incontinence:anal; necrosis:GI; obstruction:GI; perforation:GI; proctitis; stricture/stenosis (including anastomotic):GI. Adverse events are graded using Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the adverse event (AE). The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to adverse event.

2. Percentage of Patients With Any Grade 3+ Treatment-related Adverse Events [From start of treatment to the end of follow-up. Maximum follow-up at time of analysis was 10.2 years for endometrium cancer patients and 9.5 years for cervical cancer patients.]

   Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the adverse event (AE). The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE.

3. Percentage of Patients With Any Late Grade 3+ Treatment-related Adverse Events [From 91 days after start of study treatment to the end of follow-up. Maximum follow-up at time of analysis was 10.2 years for endometrium cancer patients and 9.5 years for cervical cancer patients.]

   Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each adverse events (AE) based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE. Late is defined as more than 90 days after the start of radiation therapy.

4. Percentage of Cervical Carcinoma Patients That Were Chemotherapy Compliant [From start to end of chemotherapy, approximately five weeks from registration.]

   Chemotherapy treatment was centrally reviewed for quality assurance and compliance once complete chemotherapy treatment data was received from sites.

5. Rate of Local-regional Failure at Five Years [From registration to five years.]

   Local-regional failure time is defined as time from registration to date of local-regional failure (any failure in the treatment field, which will be the pelvis only), death without local-regional failure (competing risk), or last known follow-up (censored). Local-regional failure rates are estimated by the cumulative incidence method.

6. Rate of Distant Metastases at Five Years [From registration to five years]

   Distant Metastases failure time is defined as time from registration to date of distant disease, death without distant metastases (competing risk), or last known follow-up (censored) and is estimated by the cumulative incidence method. Para-aortic nodal disease is considered to be distant disease for a cervical primary, but not for an endometrial primary.

7. Rate of Disease-free Survival at Five Years [From registration five years]

   Disease-free survival time is defined as time from registration to date of failure (any tumor recurrence, development of distant metastases or death from any cause) and is estimated by the Kaplan-Meier method. Patients last known to be alive without failure are censored at the date of last contact.

8. Rate of Overall Survival at Five Years [From randomization to five years]

   Overall survival time is defined as time from randomization to the date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Must have undergone a hysterectomy (total abdominal, vaginal, radical, or laparoscopic-assisted vaginal) within 7 weeks prior to study entry

• Patients with endometrial cancer must have also undergone a bilateral salpingo-oophorectomy

• Histologically confirmed diagnosis of 1 of the following:

• Endometrial cancer meeting 1 of the following criteria:

• Stage IB grade 3, IC grade 1-3, IIA, or IIB disease requiring postoperative pelvic radiotherapy

• Unstaged (no lymph node dissection or sampling) stage IB grade 2 disease

• Stage IIIC with all of the following:

• Pelvic lymph node positive only

• Para-aortic nodes sampled negative

• Not receiving chemotherapy

• Cervical cancer meeting 1 of the following criteria:

• Post-radical hysterectomy and requires postoperative pelvic radiotherapy due to any of the following:

• Positive pelvic nodes (negative para-aortic nodes)

• Microscopic parametrial involvement and negative margins

• Disease qualified by Sedlis criteria must have 2 of the following risk factors:

• 1/3 or more stromal invasion

• Lymph-vascular space invasion

• Large clinical tumor diameter (≥ 4 cm)

• Post-simple hysterectomy with negative margins and negative nodes by CT scan, MRI, or positron emission tomography-CT scan

• No requirement for extended-field radiotherapy beyond the pelvis

• No histologically confirmed papillary serous, clear cell, or neuroendocrine (either large or small cell) disease, endometrial stromal sarcoma, leiomyosarcoma, or malignant müllerian mixed tumor

• No evidence of metastatic disease outside of the pelvis

• No microscopic involvement of the resection margin (< 3 mm)

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-2

• WBC (white blood cell count) ≥ 4,000/mm³ (cervical cancer patients only)

• Absolute neutrophil count ≥ 1,800/mm³ (cervical cancer patients only)

• Platelet count ≥ 100,000/mm³ (cervical cancer patients only)

• Hemoglobin ≥ 8.0 g/dL (transfusion allowed)

• Serum creatinine ≤ 2.0 mg/dL (cervical cancer patients only)

• Creatinine clearance ≥ 50 mL/min (cervical cancer patients only)

• AST (aspartate aminotransferase) ≤ 2 times upper limit of normal

• Bilirubin ≤ 2 times upper limit of normal

• Patients must not exceed the weight and size limits of the treatment table or CT scanner

• No mental status changes or bladder control problems that would preclude study compliance with bladder-filling instructions

• No active inflammatory bowel disease

• No severe, active, concurrent illness, defined as 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

• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy

• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

• AIDS

• No history of allergy to cisplatin (cervical cancer patients)

• No prior invasive malignancy (except nonmelanoma skin cancer) unless disease-free for ≥ 3 years

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior radiotherapy to the pelvis that would result in overlap of radiotherapy fields

• No prior platinum-based chemotherapy (cervical cancer patients)

• No concurrent prophylactic growth factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], or pegfilgrastim)

• No concurrent prophylactic thrombopoietic agents

• No concurrent amifostine or other protective agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Auburn Radiation Oncology	Auburn	California	United States	95603
2	Radiation Oncology Centers - Cameron Park	Cameron Park	California	United States	95682
3	Mercy Cancer Center at Mercy San Juan Medical Center	Carmichael	California	United States	95608
4	East Bay Radiation Oncology Center	Castro Valley	California	United States	94546
5	Eden Medical Center	Castro Valley	California	United States	94546
6	Valley Medical Oncology Consultants - Castro Valley	Castro Valley	California	United States	94546
7	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010-3000
8	Valley Medical Oncology	Fremont	California	United States	94538
9	Rebecca and John Moores UCSD Cancer Center	La Jolla	California	United States	92093-0658
10	Highland General Hospital	Oakland	California	United States	94602
11	Alta Bates Summit Medical Center - Summit Campus	Oakland	California	United States	94609
12	Bay Area Breast Surgeons, Incorporated	Oakland	California	United States	94609
13	CCOP - Bay Area Tumor Institute	Oakland	California	United States	94609
14	Larry G Strieff MD Medical Corporation	Oakland	California	United States	94609
15	Tom K Lee, Incorporated	Oakland	California	United States	94609
16	Valley Care Medical Center	Pleasanton	California	United States	94588
17	Valley Medical Oncology Consultants - Pleasanton	Pleasanton	California	United States	94588
18	Radiation Oncology Center - Roseville	Roseville	California	United States	95661
19	Radiological Associates of Sacramento Medical Group, Incorporated	Sacramento	California	United States	95815
20	Mercy General Hospital	Sacramento	California	United States	95819
21	Veterans Affairs Medical Center - San Diego	San Diego	California	United States	92161
22	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California	United States	94115
23	Doctors Medical Center - San Pablo Campus	San Pablo	California	United States	94806
24	Solano Radiation Oncology Center	Vacaville	California	United States	95687
25	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware	United States	19958
26	CCOP - Christiana Care Health Services	Newark	Delaware	United States	19713
27	Mayo Clinic - Jacksonville	Jacksonville	Florida	United States	32224
28	Bay Medical	Panama City	Florida	United States	32401
29	St. Joseph Medical Center	Bloomington	Illinois	United States	61701
30	Graham Hospital	Canton	Illinois	United States	61520
31	Memorial Hospital	Carthage	Illinois	United States	62321
32	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611-3013
33	Alexian Brothers Radiation Oncology	Elk Grove Village	Illinois	United States	60007
34	Eureka Community Hospital	Eureka	Illinois	United States	61530
35	Galesburg Clinic, PC	Galesburg	Illinois	United States	61401
36	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
37	InterCommunity Cancer Center of Western Illinois	Galesburg	Illinois	United States	61401
38	Mason District Hospital	Havana	Illinois	United States	62644
39	Hopedale Medical Complex	Hopedale	Illinois	United States	61747
40	McDonough District Hospital	Macomb	Illinois	United States	61455
41	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois	United States	60153
42	BroMenn Regional Medical Center	Normal	Illinois	United States	61761
43	Community Cancer Center	Normal	Illinois	United States	61761
44	Saint James Hospital and Health Centers Comprehensive Cancer Institute - Olympia Fields	Olympia Fields	Illinois	United States	60461
45	Community Hospital of Ottawa	Ottawa	Illinois	United States	61350
46	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois	United States	61350
47	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois	United States	61554
48	Proctor Hospital	Peoria	Illinois	United States	61614
49	OSF St. Francis Medical Center	Peoria	Illinois	United States	61615-7827
50	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615
51	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois	United States	61615
52	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
53	Illinois Valley Community Hospital	Peru	Illinois	United States	61354
54	Perry Memorial Hospital	Princeton	Illinois	United States	61356
55	St. Margaret's Hospital	Spring Valley	Illinois	United States	61362
56	Valley Cancer Center	Spring Valley	Illinois	United States	61362
57	Cancer Institute at St. John's Hospital	Springfield	Illinois	United States	62702
58	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana	United States	46107
59	Oncology Center at Saint Margaret Mercy Healthcare Center	Hammond	Indiana	United States	46320
60	Reid Hospital & Health Care Services	Richmond	Indiana	United States	47374
61	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa	United States	52242-1002
62	Providence Medical Center	Kansas City	Kansas	United States	66112
63	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
64	Menorah Medical Center	Overland Park	Kansas	United States	66209
65	Johnson County Radiation Therapy	Overland Park	Kansas	United States	66210
66	Shawnee Mission Medical Center	Shawnee Mission	Kansas	United States	66204
67	Central Maine Comprehensive Cancer Center at Central Maine Medical Center	Lewiston	Maine	United States	04240
68	Union Hospital Cancer Program at Union Hospital	Elkton	Maryland	United States	21921
69	Dana-Farber/Brigham and Women's Cancer Center	Boston	Massachusetts	United States	02115
70	South Suburban Oncology Center	Quincy	Massachusetts	United States	02169
71	South Shore Hospital	South Weymouth	Massachusetts	United States	02190
72	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0942
73	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan	United States	48202
74	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
75	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007-3731
76	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
77	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
78	Cancer Institute of Cape Girardeau, LLC	Cape Girardeau	Missouri	United States	63703
79	Independence Regional Health Center	Independence	Missouri	United States	64050
80	Truman Medical Center - Hospital Hill	Kansas City	Missouri	United States	64108
81	Saint Luke's Cancer Institute at Saint Luke's Hospital	Kansas City	Missouri	United States	64111
82	Kansas City Cancer Center at St. Joseph's Medical Mall	Kansas City	Missouri	United States	64114
83	St. Joseph Medical Center	Kansas City	Missouri	United States	64114
84	North Kansas City Hospital	Kansas City	Missouri	United States	64116
85	Parvin Radiation Oncology	Kansas City	Missouri	United States	64116
86	CCOP - Kansas City	Kansas City	Missouri	United States	64131
87	Research Medical Center	Kansas City	Missouri	United States	64132
88	Radiation Oncology Associates of Kansas City at Northland Radiation Oncology Center	Kansas City	Missouri	United States	64154
89	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64506
90	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65802
91	St. John's Regional Health Center	Springfield	Missouri	United States	65804
92	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri	United States	65807
93	Cancer Institute of New Jersey at Cooper University Hospital - Camden	Camden	New Jersey	United States	08103
94	Monmouth Medical Center	Long Branch	New Jersey	United States	07740-6395
95	Saint Peter's University Hospital	New Brunswick	New Jersey	United States	08903
96	Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare	Vineland	New Jersey	United States	08360
97	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey	United States	08043
98	Lovelace Medical Center - Downtown	Albuquerque	New Mexico	United States	87102
99	Radiation Oncology Associates, PA	Albuquerque	New Mexico	United States	87109
100	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87131-5636
101	Cancer Institute of New Mexico	Santa Fe	New Mexico	United States	87505
102	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
103	Beth Israel Medical Center - Petrie Division	New York	New York	United States	10003-3803
104	St. Luke's - Roosevelt Hospital Center - St.Luke's Division	New York	New York	United States	10025
105	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina	United States	28233-3549
106	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio	United States	44307
107	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio	United States	44309-2090
108	Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44106-5065
109	Huron Hospital Cancer Care Center	Cleveland	Ohio	United States	44112
110	Euclid Hospital	Cleveland	Ohio	United States	44119
111	Grandview Hospital	Dayton	Ohio	United States	45405
112	Good Samaritan Hospital	Dayton	Ohio	United States	45406
113	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
114	Samaritan North Cancer Care Center	Dayton	Ohio	United States	45415
115	Veterans Affairs Medical Center - Dayton	Dayton	Ohio	United States	45428
116	CCOP - Dayton	Dayton	Ohio	United States	45429
117	Blanchard Valley Medical Associates	Findlay	Ohio	United States	45840
118	Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
119	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
120	Hillcrest Cancer Center at Hillcrest Hospital	Mayfield Heights	Ohio	United States	44124
121	Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford	Salem	Ohio	United States	44460
122	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373-1300
123	South Pointe Hospital Cancer Care Center	Warrensville Heights	Ohio	United States	44122
124	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
125	Cancer Treatment Center	Wooster	Ohio	United States	44691
126	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
127	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania	United States	19010
128	Delaware County Regional Cancer Center at Delaware County Memorial Hospital	Drexel Hill	Pennsylvania	United States	19026
129	Cancer Center of Paoli Memorial Hospital	Paoli	Pennsylvania	United States	19301-1792
130	CCOP - Main Line Health	Wynnewood	Pennsylvania	United States	19096
131	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania	United States	19096
132	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
133	Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center	Kingsport	Tennessee	United States	37662
134	M. D. Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030-4009
135	American Fork Hospital	American Fork	Utah	United States	84003
136	Sandra L. Maxwell Cancer Center	Cedar City	Utah	United States	84720
137	Jon and Karen Huntsman Cancer Center at Intermountain Medical Center	Murray	Utah	United States	84157
138	Val and Ann Browning Cancer Center at McKay-Dee Hospital Center	Ogden	Utah	United States	84403
139	Utah Valley Regional Medical Center - Provo	Provo	Utah	United States	84604
140	Dixie Regional Medical Center - East Campus	Saint George	Utah	United States	84770
141	LDS Hospital	Salt Lake City	Utah	United States	84103
142	Utah Cancer Specialists at UCS Cancer Center	Salt Lake City	Utah	United States	84106
143	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah	United States	84112
144	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont	United States	05401
145	Southwest Virginia Regional Cancer Center at Wellmonth Health	Norton	Virginia	United States	24273
146	CCOP - Virginia Mason Research Center	Seattle	Washington	United States	98101
147	Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
148	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin	United States	53792-6164
149	Columbia Saint Mary's Hospital - Ozaukee	Mequon	Wisconsin	United States	53097
150	Columbia-Saint Mary's Cancer Care Center	Milwaukee	Wisconsin	United States	53211
151	University of Wisconcin Cancer Center at Aspirus Wausau Hospital	Wausau	Wisconsin	United States	54401
152	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
153	McGill Cancer Centre at McGill University	Montreal	Quebec	Canada	H2W 1S6

Sponsors and Collaborators

• Radiation Therapy Oncology Group
• National Cancer Institute (NCI)
• NRG Oncology

Investigators

• Study Chair: Anuja Jhingran, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Radiation Therapy Oncology Group
• ClinicalTrials.gov Identifier: NCT00331760
• Other Study ID Numbers: RTOG-0418; CDR0000472905
• First Posted: May 31, 2006
• Last Update Posted: Feb 26, 2019
• Last Verified: Feb 1, 2019

• Keywords provided by Radiation Therapy Oncology Group: stage I endometrial carcinoma; stage II endometrial carcinoma; stage III endometrial carcinoma; endometrial adenoacanthoma; endometrial adenocarcinoma; endometrial adenosquamous cell carcinoma; stage IB cervical cancer; stage IIA cervical cancer; stage IIB cervical cancer; cervical adenocarcinoma; cervical adenosquamous cell carcinoma; cervical squamous cell carcinoma
• Additional relevant MeSH terms: Uterine Cervical Neoplasms; Endometrial Neoplasms; Cisplatin

Study Results

Participant Flow

Arm/Group Title	Endometrial Cancer: IMRT	Cervical Cancer: IMRT + Chemotherapy (Cisplatin)
Arm/Group Description	Endometrial Cancer patients receive Intensity Modulated Radiation Therapy (IMRT)	Cervical patients receive Intensity Modulated Radiation Therapy (IMRT) + Chemotherapy (cisplatin)
Period Title: Overall Study
STARTED	58	48
COMPLETED	43	40
NOT COMPLETED	15	8

Baseline Characteristics

Arm/Group Title	Endometrial Cancer: IMRT	Cervical Cancer: IMRT + Chemotherapy (Cisplatin)	Total
Arm/Group Description	Endometrial Cancer patients receive Intensity Modulated Radiation Therapy (IMRT)	Cervical patients receive Intensity Modulated Radiation Therapy (IMRT) + Chemotherapy (cisplatin)	Total of all reporting groups
Overall Participants	58	48	106
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	58	43	53
Sex: Female, Male (Count of Participants)
Female	58 100%	48 100%	106 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Reproducibility of Radiation Technique (Number of Unacceptable Deviations in Central IMRT Quality Assurance Review)
Description	Central quality assurance review of the IMRT planning and dosing categorized unacceptable deviations (UD) from protocol compliance with the delineation of planning target volume for the vagina and pelvic lymph nodes. Each arm of this study is considered independently, they are not compared to each other. The study was designed such that, for each arm, 5 or more of 42 subjects scored as unacceptable would determine the respective treatment technique as not reproducible. For each arm this design provides 90% power with a 0.05 type I error to reject the null hypothesis that the true probability of concluding the given technique to be reproducible is <= 80%. The alternative hypothesis is that the true probability is >= 95%. For [vagina / pelvic lymph nodes]: UD is defined as: The 90% isodose surface covers < 95% of [internal target volume (ITV)/ planned target volume (PTV)] 50.4 or > 5% of the [ITV/PTV] 50.4 receives over 115%.
Time Frame	IMRT planning and dosing data is centrally reviewed for quality assurance after treatment delivery.

Outcome Measure Data

Analysis Population Description

All eligible patients.

Arm/Group Title	Endometrial Cancer: IMRT	Cervical Cancer: IMRT + Chemotherapy (Cisplatin)
Arm/Group Description	Endometrial Cancer patients receive Intensity Modulated Radiation Therapy (IMRT)	Cervical patients receive Intensity Modulated Radiation Therapy (IMRT) + Chemotherapy (cisplatin)
Measure Participants	43	40
Number [participants]	1 1.7%	0 0%

2. Secondary Outcome

Title	Percentage of Patients With Grade 2+ Bowel Adverse Events
Description	Bowel adverse events are defined as any of the following adverse events: diarrhea; enteritis; fistula; ileus:gastrointestinal (GI); incontinence:anal; necrosis:GI; obstruction:GI; perforation:GI; proctitis; stricture/stenosis (including anastomotic):GI. Adverse events are graded using Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the adverse event (AE). The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to adverse event.
Time Frame	From the start of treatment to 90 days.

Outcome Measure Data

Analysis Population Description

Eligible patients who started study treatment

Arm/Group Title	Endometrial Cancer: IMRT	Cervical Cancer: IMRT + Chemotherapy (Cisplatin)
Arm/Group Description	Endometrial Cancer patients receive Intensity Modulated Radiation Therapy (IMRT)	Cervical patients receive Intensity Modulated Radiation Therapy (IMRT) + Chemotherapy (cisplatin)
Measure Participants	43	40
Number (95% Confidence Interval) [percentage of participants]	27.9 48.1%	22.5 46.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Endometrial Cancer: IMRT
	Comments	A sample size of 42 patients provides 64% power to detect a reduction in short-term grade 2 or higher bowel AEs from historical rate of 40% to 25%.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.12
	Comments
	Method	Chi-squared
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cervical Cancer: IMRT + Chemotherapy (Cisplatin)
	Comments	A sample size of 42 patients provides 88% power to detect a reduction in short-term grade 2 or higher bowel AEs from historical rate of 40% to 20%.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.043
	Comments
	Method	Chi-squared
	Comments

3. Secondary Outcome

Title	Percentage of Patients With Any Grade 3+ Treatment-related Adverse Events
Description	Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the adverse event (AE). The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE.
Time Frame	From start of treatment to the end of follow-up. Maximum follow-up at time of analysis was 10.2 years for endometrium cancer patients and 9.5 years for cervical cancer patients.

Outcome Measure Data

Analysis Population Description

Eligible patients who started study treatment

Arm/Group Title	Endometrial Cancer: IMRT	Cervical Cancer: IMRT + Chemotherapy (Cisplatin)
Arm/Group Description	Endometrial Cancer patients receive Intensity Modulated Radiation Therapy (IMRT)	Cervical patients receive Intensity Modulated Radiation Therapy (IMRT) + Chemotherapy (cisplatin)
Measure Participants	43	40
Non-hematologic	19 32.8%	30 62.5%
Overall	30 51.7%	48 100%

4. Secondary Outcome

Title	Percentage of Patients With Any Late Grade 3+ Treatment-related Adverse Events
Description	Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each adverse events (AE) based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE. Late is defined as more than 90 days after the start of radiation therapy.
Time Frame	From 91 days after start of study treatment to the end of follow-up. Maximum follow-up at time of analysis was 10.2 years for endometrium cancer patients and 9.5 years for cervical cancer patients.

Outcome Measure Data

Analysis Population Description

Eligible patients who started study treatment

Arm/Group Title	Endometrial Cancer: IMRT	Cervical Cancer: IMRT + Chemotherapy (Cisplatin)
Arm/Group Description	Endometrial Cancer patients receive Intensity Modulated Radiation Therapy (IMRT)	Cervical patients receive Intensity Modulated Radiation Therapy (IMRT) + Chemotherapy (cisplatin)
Measure Participants	43	40
Non-hematologic	12 20.7%	10 20.8%
Overall	12 20.7%	10 20.8%

5. Secondary Outcome

Title	Percentage of Cervical Carcinoma Patients That Were Chemotherapy Compliant
Description	Chemotherapy treatment was centrally reviewed for quality assurance and compliance once complete chemotherapy treatment data was received from sites.
Time Frame	From start to end of chemotherapy, approximately five weeks from registration.

Outcome Measure Data

Analysis Population Description

Eligible patients in the chemotherapy group (cervical cancer patients) who started study treatment

Arm/Group Title	Cervical Cancer: IMRT + Chemotherapy (Cisplatin)
Arm/Group Description	Cervical patients receive Intensity Modulated Radiation Therapy (IMRT) + Chemotherapy (cisplatin)
Measure Participants	40
Number (95% Confidence Interval) [percentage of participants]	80 137.9%

6. Secondary Outcome

Title	Rate of Local-regional Failure at Five Years
Description	Local-regional failure time is defined as time from registration to date of local-regional failure (any failure in the treatment field, which will be the pelvis only), death without local-regional failure (competing risk), or last known follow-up (censored). Local-regional failure rates are estimated by the cumulative incidence method.
Time Frame	From registration to five years.

Outcome Measure Data

Analysis Population Description

Eligible patients who started study treatment

Arm/Group Title	Endometrial Cancer: IMRT	Cervical Cancer: IMRT + Chemotherapy (Cisplatin)
Arm/Group Description	Endometrial Cancer patients receive Intensity Modulated Radiation Therapy (IMRT)	Cervical patients receive Intensity Modulated Radiation Therapy (IMRT) + Chemotherapy (cisplatin)
Measure Participants	43	40
Number (95% Confidence Interval) [percentage of participants]	5 8.6%	8 16.7%

7. Secondary Outcome

Title	Rate of Distant Metastases at Five Years
Description	Distant Metastases failure time is defined as time from registration to date of distant disease, death without distant metastases (competing risk), or last known follow-up (censored) and is estimated by the cumulative incidence method. Para-aortic nodal disease is considered to be distant disease for a cervical primary, but not for an endometrial primary.
Time Frame	From registration to five years

Outcome Measure Data

Analysis Population Description

Eligible patients who started study treatment

Arm/Group Title	Endometrial Cancer: IMRT	Cervical Cancer: IMRT + Chemotherapy (Cisplatin)
Arm/Group Description	Endometrial Cancer patients receive Intensity Modulated Radiation Therapy (IMRT)	Cervical patients receive Intensity Modulated Radiation Therapy (IMRT) + Chemotherapy (cisplatin)
Measure Participants	43	40
Number (95% Confidence Interval) [percentage of participants]	7 12.1%	14 29.2%

8. Secondary Outcome

Title	Rate of Disease-free Survival at Five Years
Description	Disease-free survival time is defined as time from registration to date of failure (any tumor recurrence, development of distant metastases or death from any cause) and is estimated by the Kaplan-Meier method. Patients last known to be alive without failure are censored at the date of last contact.
Time Frame	From registration five years

Outcome Measure Data

Analysis Population Description

Eligible patients who started study treatment

Arm/Group Title	Endometrial Cancer: IMRT	Cervical Cancer: IMRT + Chemotherapy (Cisplatin)
Arm/Group Description	Endometrial Cancer patients receive Intensity Modulated Radiation Therapy (IMRT)	Cervical patients receive Intensity Modulated Radiation Therapy (IMRT) + Chemotherapy (cisplatin)
Measure Participants	43	40
Number (95% Confidence Interval) [percentage of participants]	88 151.7%	84 175%

9. Secondary Outcome

Title	Rate of Overall Survival at Five Years
Description	Overall survival time is defined as time from randomization to the date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.
Time Frame	From randomization to five years

Outcome Measure Data

Analysis Population Description

Eligible patients who started study treatment

Arm/Group Title	Endometrial Cancer: IMRT	Cervical Cancer: IMRT + Chemotherapy (Cisplatin)
Arm/Group Description	Endometrial Cancer patients receive Intensity Modulated Radiation Therapy (IMRT)	Cervical patients receive Intensity Modulated Radiation Therapy (IMRT) + Chemotherapy (cisplatin)
Measure Participants	43	40
Number (95% Confidence Interval) [percentage of participants]	88 151.7%	92 191.7%

Adverse Events

Adverse Event Reporting Description	Eligible patients who started study treatment are included. Patients experiencing more than one of a given adverse event are counted only once for that adverse event.
Arm/Group Title	Endometrial Cancer: IMRT		Cervical Cancer: IMRT + Chemotherapy (Cisplatin)
Arm/Group Description	Endometrial Cancer patients receive Intensity Modulated Radiation Therapy (IMRT)		Cervical patients receive Intensity Modulated Radiation Therapy (IMRT) + Chemotherapy (cisplatin)
All Cause Mortality
	Endometrial Cancer: IMRT		Cervical Cancer: IMRT + Chemotherapy (Cisplatin)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Endometrial Cancer: IMRT		Cervical Cancer: IMRT + Chemotherapy (Cisplatin)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/43 (4.7%)		3/40 (7.5%)
Gastrointestinal disorders
Diarrhoea NOS	1/43 (2.3%)		1/40 (2.5%)
Nausea	1/43 (2.3%)		1/40 (2.5%)
Rectal hemorrhage	0/43 (0%)		1/40 (2.5%)
Vomiting NOS	0/43 (0%)		1/40 (2.5%)
General disorders
Fatigue	0/43 (0%)		1/40 (2.5%)
Infections and infestations
Urinary tract infection NOS	1/43 (2.3%)		0/40 (0%)
Investigations
Lymphopenia	0/43 (0%)		1/40 (2.5%)
Neutrophil count	0/43 (0%)		1/40 (2.5%)
Metabolism and nutrition disorders
Dehydration	0/43 (0%)		1/40 (2.5%)
Hypocalcemia	0/43 (0%)		1/40 (2.5%)
Hypokalemia	0/43 (0%)		1/40 (2.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/43 (2.3%)		0/40 (0%)
Nervous system disorders
Peripheral sensory neuropathy	0/43 (0%)		1/40 (2.5%)
Psychiatric disorders
Depression	1/43 (2.3%)		0/40 (0%)
Other (Not Including Serious) Adverse Events
	Endometrial Cancer: IMRT		Cervical Cancer: IMRT + Chemotherapy (Cisplatin)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/43 (97.7%)		39/40 (97.5%)
Blood and lymphatic system disorders
Hemoglobin	11/43 (25.6%)		21/40 (52.5%)
Ear and labyrinth disorders
Hearing impaired	0/43 (0%)		3/40 (7.5%)
Tinnitus	1/43 (2.3%)		5/40 (12.5%)
Gastrointestinal disorders
Abdominal distention	1/43 (2.3%)		3/40 (7.5%)
Abdominal pain NOS	12/43 (27.9%)		10/40 (25%)
Anal discomfort	1/43 (2.3%)		2/40 (5%)
Constipation	5/43 (11.6%)		8/40 (20%)
Diarrhoea NOS	33/43 (76.7%)		33/40 (82.5%)
Dyspepsia	3/43 (7%)		2/40 (5%)
Dysphagia	0/43 (0%)		2/40 (5%)
Enteritis	6/43 (14%)		2/40 (5%)
Flatulence	1/43 (2.3%)		2/40 (5%)
Gastritis NOS	0/43 (0%)		2/40 (5%)
Nausea	14/43 (32.6%)		27/40 (67.5%)
Proctitis NOS	1/43 (2.3%)		5/40 (12.5%)
Vomiting NOS	1/43 (2.3%)		14/40 (35%)
General disorders
Fatigue	20/43 (46.5%)		27/40 (67.5%)
Pain NOS	3/43 (7%)		1/40 (2.5%)
Infections and infestations
Gingival infection	0/43 (0%)		2/40 (5%)
Urinary tract infection NOS	0/43 (0%)		3/40 (7.5%)
Injury, poisoning and procedural complications
Dermatitis radiation NOS	6/43 (14%)		6/40 (15%)
Fracture NOS	2/43 (4.7%)		2/40 (5%)
Radiation recall syndrome	1/43 (2.3%)		2/40 (5%)
Investigations
Alanine aminotransferase increased	4/43 (9.3%)		5/40 (12.5%)
Aspartate aminotransferase increased	3/43 (7%)		1/40 (2.5%)
Blood alkaline phosphatase increased	3/43 (7%)		2/40 (5%)
Blood bilirubin increased	1/43 (2.3%)		2/40 (5%)
Blood creatinine increased	0/43 (0%)		3/40 (7.5%)
Leukopenia NOS	17/43 (39.5%)		26/40 (65%)
Lymphopenia	9/43 (20.9%)		18/40 (45%)
Neutrophil count	3/43 (7%)		5/40 (12.5%)
Platelet count decreased	7/43 (16.3%)		11/40 (27.5%)
Weight decreased	4/43 (9.3%)		5/40 (12.5%)
Metabolism and nutrition disorders
Anorexia	4/43 (9.3%)		9/40 (22.5%)
Dehydration	1/43 (2.3%)		2/40 (5%)
Hyperglycaemia NOS	10/43 (23.3%)		7/40 (17.5%)
Hypoalbuminemia	3/43 (7%)		5/40 (12.5%)
Hypokalemia	5/43 (11.6%)		9/40 (22.5%)
Hypomagnesemia	5/43 (11.6%)		6/40 (15%)
Hyponatremia	2/43 (4.7%)		5/40 (12.5%)
Musculoskeletal and connective tissue disorders
Back pain	5/43 (11.6%)		5/40 (12.5%)
Buttock pain	0/43 (0%)		2/40 (5%)
Pain in extremity	5/43 (11.6%)		3/40 (7.5%)
Nervous system disorders
Dizziness	1/43 (2.3%)		2/40 (5%)
Dysgeusia	1/43 (2.3%)		6/40 (15%)
Headache	0/43 (0%)		4/40 (10%)
Peripheral sensory neuropathy	6/43 (14%)		5/40 (12.5%)
Psychiatric disorders
Agitation	0/43 (0%)		2/40 (5%)
Anxiety	1/43 (2.3%)		6/40 (15%)
Depression	7/43 (16.3%)		3/40 (7.5%)
Insomnia	0/43 (0%)		6/40 (15%)
Libido decreased	3/43 (7%)		3/40 (7.5%)
Renal and urinary disorders
Bladder spasm	0/43 (0%)		3/40 (7.5%)
Cystitis NOS	3/43 (7%)		7/40 (17.5%)
Pollakiuria	10/43 (23.3%)		10/40 (25%)
Urethral pain	1/43 (2.3%)		3/40 (7.5%)
Urinary incontinence	9/43 (20.9%)		7/40 (17.5%)
Urinary retention	1/43 (2.3%)		4/40 (10%)
Reproductive system and breast disorders
Pelvic pain NOS	3/43 (7%)		5/40 (12.5%)
Vaginal atresia	6/43 (14%)		14/40 (35%)
Vaginal discharge	3/43 (7%)		8/40 (20%)
Vaginal hemorrhage	1/43 (2.3%)		4/40 (10%)
Vaginal pain	2/43 (4.7%)		4/40 (10%)
Vaginal stricture	3/43 (7%)		0/40 (0%)
Vaginitis	3/43 (7%)		2/40 (5%)
Vulvovaginal dryness	4/43 (9.3%)		6/40 (15%)
Skin and subcutaneous tissue disorders
Alopecia	1/43 (2.3%)		3/40 (7.5%)
Erythema multiforme	0/43 (0%)		2/40 (5%)
Telangiectasia	3/43 (7%)		2/40 (5%)
Vascular disorders
Hot flushes NOS	4/43 (9.3%)		19/40 (47.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.