Chemotherapy and Radiation Therapy With or Without Surgery in Treating Patients With Head and Neck Cancer

• Sponsor: Radiation Therapy Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00047008
• Collaborator: National Cancer Institute (NCI) (NIH), NRG Oncology (Other)
• Enrollment: 743
• Locations: 195
• Arms: 2
• Actual Duration (Months): 238.6
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Radiation therapy (RT) uses high-energy x-rays to damage tumor cells. Giving radiation therapy in different ways and combining it with chemotherapy before surgery may kill more tumor cells. It is not yet known which radiation therapy regimen combined with chemotherapy with or without surgery is more effective for head and neck cancer.

PURPOSE: Randomized phase III trial to compare two different radiation therapy regimens combined with cisplatin with or without surgery in treating patients who have stage III or stage IV head and neck cancer.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer	Drug: cisplatin; Radiation: Standard fractionation RT; Radiation: Accelerated fractionation radiation therapy; Procedure: Conventional surgery for select patients	Phase 3

Detailed Description

OBJECTIVES:

Primary

• Compare overall survival of patients with stage III or IV squamous cell carcinoma of the head and neck treated with conventional vs accelerated radiotherapy and concurrent cisplatin with or without surgical resection.

Secondary

• Compare local-regional control of disease and disease-free rates in patients treated with these regimens.

• Compare the acute and late toxicity of these regimens in these patients.

• Compare quality of life, perception of side effects, and performance status of patients treated with these regimens.

• Determine whether epidermal growth factor receptor and cyclo-oxygenase-2 expressions are independent prognostic markers in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to tumor site (larynx vs other), nodal stage (N0 vs N1 or N2a or N2b vs N2c or N3), and Zubrod performance status (0 vs 1). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo standard fractionation radiotherapy 5 days a week for 7 weeks. Patients also receive cisplatin IV on days 1, 22, and 43.

• Arm II: Patients undergo accelerated fractionation radiotherapy 5 days a week for 3.5 weeks and then twice a day, 5 days a week, for 2.5 weeks. Patients also receive cisplatin IV on days 1 and 22.

Patients with biopsy-proven relapsed disease more than 3 months after completion of therapy undergo surgical resection of the primary tumor.

Quality of life is assessed at baseline, during one of the last 2 weeks of treatment, at 3 and 12 months, and then annually for 4 years.

Patients are followed at 6-8 weeks, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 720 patients (360 per treatment arm) will be accrued for this study within 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 743 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III Trial of Concurrent Radiation and Chemotherapy for Advanced Head and Neck Carcinomas
• Actual Study Start Date: Jul 1, 2002
• Actual Primary Completion Date: Jun 1, 2010
• Actual Study Completion Date: May 20, 2022

Arms and Interventions

Arm	Intervention/Treatment
Other: Standard fractionation RT + cisplatin Standard fractionation radiation therapy with concurrent cisplatin followed by conventional surgery for select patients.	Drug: cisplatin; 100 mg/m^2 intravenously on days 1, 22; Radiation: Standard fractionation RT; Radiation will be delivered in 2 Gy per fraction, five fractions a week. The primary tumor and clinically/radiologically involved nodes will receive 70 Gy in 7 weeks and uninvolved nodes will receive 50 Gy in 5 weeks. The anterior lower neck field will be treated with 2 Gy per fraction at 3-cm depth to a total dose of 50 Gy.; Procedure: Conventional surgery for select patients; Surgical removal (salvage resection) of the primary tumor should be performed if biopsy-proven cancer remains more than three months after completion of therapy. The nature of the surgical resection should be dictated by the extent of tumor at the initial evaluation. The operation should be conducted using accepted criteria for primary surgical treatment of the cancer. A planned neck dissection for patients with multiple neck nodes or with lymph nodes exceeding 3 cm in diameter (N2a, N2b, N3) is mandatory, regardless of the clinical and/or radiographic response. A neck dissection is required for patients with N1 disease if a palpable or worrisome radiographic abnormality persists in the neck six weeks after completion of therapy. Surgery should be performed within 2 weeks once the decision for neck dissection is made.
Experimental: Accelerated fractionation RT + cisplatin Accelerated fractionation radiation therapy by concomitant boost with concurrent cisplatin followed by conventional surgery for select patients.	Drug: cisplatin; 100 mg/m^2 intravenously on days 1, 22; Radiation: Accelerated fractionation radiation therapy; Radiation to the initial target volume encompassing the gross and subclinical disease sites will be delivered in 1.8 Gy per fraction, five fractions a week to 54 Gy in 30 fractions over 6 weeks. At 32.4 Gy/18 Fx (i.e., latter part of week 4), the boost volume covering gross tumor and clinically/radiologically involved nodes will receive boost irradiation of 1.5 Gy/Fx as second daily fraction (at least 6 h interval) for a total of 12 treatment days (18 Gy total). The primary tumor and clinically/radiologically involved nodes will receive 72 Gy in 42 fractions over 6 weeks and uninvolved nodes will receive 54 Gy in 6 weeks. Clinically/radiologically negative posterior neck should receive a minimum dose of 50.4 Gy at 3 cm. The anterior lower neck field will be treated with 1.8 Gy per fraction at 3-cm depth to a total dose of 50.4 Gy in 28 fractions in 5.6 weeks.; Procedure: Conventional surgery for select patients; Surgical removal (salvage resection) of the primary tumor should be performed if biopsy-proven cancer remains more than three months after completion of therapy. The nature of the surgical resection should be dictated by the extent of tumor at the initial evaluation. The operation should be conducted using accepted criteria for primary surgical treatment of the cancer. A planned neck dissection for patients with multiple neck nodes or with lymph nodes exceeding 3 cm in diameter (N2a, N2b, N3) is mandatory, regardless of the clinical and/or radiographic response. A neck dissection is required for patients with N1 disease if a palpable or worrisome radiographic abnormality persists in the neck six weeks after completion of therapy. Surgery should be performed within 2 weeks once the decision for neck dissection is made.

Outcome Measures

Primary Outcome Measures

1. Overall Survival (3-year Rate) [From randomization to date of death or last follow-up. Analysis occurs after 309 deaths have been reported.]

   Time from randomization to death due to any cause or last known date alive. Median survival was not reached, therefore 3-year survival rates are reported.

Secondary Outcome Measures

1. Local-regional Control [From randomization to date of failure]

   From randomization to date of failure (local or regional persistence/relapse) or death or last follow-up. Analysis occurs after 309 deaths have been reported.

2. Disease-free Survival [From randomization to date of failure]

   From randomization to date of failure (local or regional persistence/relapse, distant metastasis, secondary primary tumor or death) or last follow-up. Analysis occurs after 309 deaths have been reported.

3. Rate of Grade 3-5 Toxicity [From start of treatment to last follow-up]

4. Quality of Life [From randomization to 5 years]

5. Correlation of Epidermal Growth Factor Receptor(EGFR) With Outcomes [From randomization to date of death or last follow-up]

6. Correlation of COX-2 With Outcomes [From randomization to date of death or last follow-up]

Eligibility Criteria

Criteria

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

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx

• Stage III or IV (T2, N2-3, M0 or T3-4, any N, M0)

• No metastases below the clavicle or more distant by clinical exam or radiology

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute granulocyte count at least 2,000/mm^3

• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 1.5 mg/dL

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) no greater than 2 times upper limit of normal

Renal

• Creatinine no greater than 1.5 mg/dL

• Creatinine clearance at least 50 mL/min

• Calcium normal

Cardiovascular

• No symptomatic coronary artery disease (angina)

• No myocardial infarction within the past 6 months

Other

• No other invasive malignancy within the past 3 years except nonmelanoma skin cancer

• No simultaneous primary tumors

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy to the head and neck except radioactive iodine therapy

Surgery

• No prior surgery to the primary tumor or nodes except diagnostic biopsy or nodal sampling of neck disease

• No radical or modified neck dissection

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Comprehensive Cancer Center at University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Mobile Infirmary Medical Center	Mobile	Alabama	United States	36607
3	Foundation for Cancer Research and Education	Phoenix	Arizona	United States	85013
4	CCOP - Mayo Clinic Scottsdale Oncology Program	Scottsdale	Arizona	United States	85259
5	Scottsdale Healthcare - Shea	Scottsdale	Arizona	United States	85260
6	Virginia G. Piper Cancer Center at Scottsdale Healthcare - Osborn	Scottsdale	Arizona	United States	85260
7	Providence Saint Joseph Medical Center - Burbank	Burbank	California	United States	91505
8	Saint Rose Hospital	Hayward	California	United States	94545
9	Cancer Care Consultants Medical Associates at Daniel Freeman Memorial Hospital	Inglewood	California	United States	90301
10	Valley Memorial Hospital	Livermore	California	United States	94550
11	Loma Linda University Cancer Institute at Loma Linda University Medical Center	Loma Linda	California	United States	92354
12	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California	United States	90033-0804
13	Providence Holy Cross Cancer Center	Mission Hills	California	United States	91346-9600
14	Highland General Hospital	Oakland	California	United States	94602
15	CCOP - Bay Area Tumor Institute	Oakland	California	United States	94609
16	Summit Medical Center	Oakland	California	United States	94609
17	Pomona Valley Hospital Medical Center	Pomona	California	United States	91767
18	Radiological Associates of Sacramento Medical Group, Inc.	Sacramento	California	United States	95815
19	University of California Davis Cancer Center	Sacramento	California	United States	95817
20	Naval Medical Center - San Diego	San Diego	California	United States	92134
21	J.C. Robinson, M.D. Regional Cancer Center	San Pablo	California	United States	94806
22	Memorial Hospital Cancer Center	Colorado Springs	Colorado	United States	80909
23	University of Colorado Cancer Center at University of Colorado Health Sciences Center	Denver	Colorado	United States	80217-3364
24	Beebe Medical Center	Lewes	Delaware	United States	19958
25	CCOP - Christiana Care Health Services	Newark	Delaware	United States	19718
26	St. Francis Hospital	Wilmington	Delaware	United States	19805
27	Michael & Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital	Fort Lauderdale	Florida	United States	33308
28	21st Century Oncology - Fort Myers	Fort Myers	Florida	United States	33901
29	Shands Cancer Center at the University of Florida - Jacksonville	Gainesville	Florida	United States	32610
30	Memorial Cancer Institute at Memorial Regional Hospital	Hollywood	Florida	United States	33021
31	Baptist Cancer Institute - Jacksonville	Jacksonville	Florida	United States	32207
32	University of Florida Shands Cancer Center	Jacksonville	Florida	United States	32209
33	Ella Milbank Foshay Cancer Center at Jupiter Medical Center	Jupiter	Florida	United States	33458
34	CCOP - Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
35	Gulf Coast Cancer Treatment Center	Panama City	Florida	United States	32405
36	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida	Tampa	Florida	United States	33612
37	Georgia Cancer Center for Excellence at Grady Memorial Hospital	Atlanta	Georgia	United States	30303
38	Emory University Hospital - Atlanta	Atlanta	Georgia	United States	30322
39	John B. Amos Community Cancer Center	Columbus	Georgia	United States	31904
40	Northeast Georgia Medical Center	Gainesville	Georgia	United States	30501
41	Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia	United States	31403
42	Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center	Boise	Idaho	United States	83706
43	Northwest Community Hospital	Arlington Heights	Illinois	United States	60005
44	Mount Sinai Hospital Medical Center	Chicago	Illinois	United States	60608
45	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611
46	Creticos Cancer Center at Advocate Illinois Masonic Medical Center	Chicago	Illinois	United States	60657
47	Cancer Care Center at Advocate Good Samaritan Hospital	Downers Grove	Illinois	United States	60515
48	Alexian Brothers Cancer Care Center	Elk Grove Village	Illinois	United States	60007
49	Ingalls Cancer Care Center at Ingalls Memorial Hospital	Harvey	Illinois	United States	60426
50	St. John's Cancer Center at St. John's Medical Center	Anderson	Indiana	United States	46016
51	St. Francis Hospital and Health Centers	Beech Grove	Indiana	United States	46107
52	Elkhart General Hospital	Elkhart	Indiana	United States	46515
53	Indiana University Cancer Center	Indianapolis	Indiana	United States	46202
54	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana	United States	46350
55	Saint Joseph Regional Medical Center - Plymouth Campus	Plymouth	Indiana	United States	46544
56	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
57	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
58	Wendt Regional Cancer Center at Finley Hospital	Dubuque	Iowa	United States	52001
59	Cancer Treatment Center at the Medical Center - Bowling Green	Bowling Green	Kentucky	United States	42101
60	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky	United States	40536
61	James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky	United States	40202
62	Baton Rouge General Regional Cancer Center	Baton Rouge	Louisiana	United States	70806
63	Mary Bird Perkins Cancer Center - Baton Rouge	Baton Rouge	Louisiana	United States	70809
64	Cancer Center at Medical Center of Louisiana - New Orleans	New Orleans	Louisiana	United States	70112
65	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana	United States	70112
66	Tulane Cancer Center	New Orleans	Louisiana	United States	70112
67	New Orleans Cancer Institute at Memorial Medical Center	New Orleans	Louisiana	United States	70115
68	DeCesaris Cancer Institute at Anne Arundel Medical Center	Annapolis	Maryland	United States	21401
69	Union Hospital Cancer Center at Union Hospital	Elkton	Maryland	United States	21921
70	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
71	Cancer Research Center at Boston Medical Center	Boston	Massachusetts	United States	02118
72	Hudner Oncology Center at Saint Anne's Hospital	Fall River	Massachusetts	United States	02721
73	Cape Cod Hospital	Hyannis	Massachusetts	United States	02601
74	South Suburban Oncology Center	Quincy	Massachusetts	United States	02169
75	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48100
76	St. Joseph Mercy Cancer Center at St. Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106-0995
77	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48123
78	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
79	Van Elslander Cancer Center at St. John Hospital and Medical Center	Detroit	Michigan	United States	48236
80	Hurley Medical Center	Flint	Michigan	United States	48502
81	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48532
82	Great Lakes Cancer Institute at McLaren Regional Medical Center	Flint	Michigan	United States	48532
83	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
84	CCOP - Kalamazoo	Kalamazoo	Michigan	United States	49001
85	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
86	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
87	Seton Cancer Institute - Saginaw	Saginaw	Michigan	United States	48601
88	St. John Macomb Hospital	Warren	Michigan	United States	48903
89	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
90	Cancer Institute of Cape Girardeau	Cape Girardeau	Missouri	United States	63703
91	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri	United States	65203
92	CCOP - Kansas City	Kansas City	Missouri	United States	64131
93	Saint Louis University Cancer Center	Saint Louis	Missouri	United States	63110
94	Siteman Cancer Center at Barnes-Jewish Hospital	Saint Louis	Missouri	United States	63110
95	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65802
96	St. John's Regional Health Center	Springfield	Missouri	United States	65804
97	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri	United States	65807
98	Methodist Hospital Cancer Center at Nebraska Methodist Hospital - Omaha	Omaha	Nebraska	United States	68114
99	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
100	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
101	Washoe Cancer Services at Washoe Medical Center - Reno	Reno	Nevada	United States	89502
102	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
103	Cancer Institute of New Jersey at the Cooper University Hospital	Camden	New Jersey	United States	08103
104	Monmouth Medical Center	Long Branch	New Jersey	United States	07740
105	South Jersey Healthcare Regional Cancer Center	Millville	New Jersey	United States	08332
106	Fox Chase Virtua Health Cancer Program - Marlton	Mount Holly	New Jersey	United States	08060
107	Community Medical Center	Toms River	New Jersey	United States	08755
108	New York Methodist Hospital	Brooklyn	New York	United States	11215
109	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
110	CCOP - North Shore University Hospital	Manhasset	New York	United States	11030
111	Fitzpatrick Cancer Center at Champlain Valley Physicians Hospital Medical Center	Plattsburgh	New York	United States	12901
112	SUNY Upstate Medical University Hospital	Syracuse	New York	United States	13210
113	Randolph Hospital	Asheboro	North Carolina	United States	27203
114	John Smith, Jr./Dalton McMichael Cancer Center at Morehead Memorial Hospital	Eden	North Carolina	United States	27288
115	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina	United States	27534
116	Wayne Radiation Oncology	Goldsboro	North Carolina	United States	27534
117	Moses Cone Regional Cancer Center at Wesley Long Community Hospital	Greensboro	North Carolina	United States	27401
118	Annie Penn Cancer Center	Reidsville	North Carolina	United States	27320
119	Rutherford Hospital	Rutherfordton	North Carolina	United States	28139
120	Wilson Medical Center	Wilson	North Carolina	United States	27893
121	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina	United States	27157
122	Trinity Cancer Care Center	Minot	North Dakota	United States	58701
123	Akron City Hospital at Summa Health System	Akron	Ohio	United States	44304
124	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio	United States	44307
125	Aultman Hospital Cancer Center at Aultman Health Foundation	Canton	Ohio	United States	44710-1799
126	Grandview Hospital	Dayton	Ohio	United States	45405
127	Good Samaritan Hospital	Dayton	Ohio	United States	45406
128	Miami Valley Hospital	Dayton	Ohio	United States	45409
129	Samaritan North Cancer Care Center	Dayton	Ohio	United States	45415
130	Veterans Affairs Medical Center - Dayton	Dayton	Ohio	United States	45428
131	CCOP - Dayton	Dayton	Ohio	United States	45429
132	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
133	St. Rita's Medical Center	Lima	Ohio	United States	45801
134	Middletown Regional Hospital	Middletown	Ohio	United States	45044
135	Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford	Salem	Ohio	United States	44460
136	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373
137	Cancer Treatment Center	Wooster	Ohio	United States	44691
138	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
139	LaFortune Cancer Center at St. John Health System	Tulsa	Oklahoma	United States	74104
140	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma	United States	74136
141	Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
142	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania	United States	19010
143	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
144	Cancer Center at Paoli Memorial Hospital	Paoli	Pennsylvania	United States	19301
145	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania	United States	19107
146	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111-2497
147	Albert Einstein Cancer Center	Philadelphia	Pennsylvania	United States	19141
148	Mercy Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15219
149	Mercy Hospital Cancer Center - Scranton	Scranton	Pennsylvania	United States	18501
150	CCOP - MainLine Health	Wynnewood	Pennsylvania	United States	19096
151	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania	United States	19096
152	Rose Ramer Cancer Clinic at Anderson Area Medical Center	Anderson	South Carolina	United States	29621
153	Bon Secours St. Francis Health System	Greenville	South Carolina	United States	29601
154	Greenville Hospital System Cancer Center	Greenville	South Carolina	United States	29605
155	CCOP - Greenville	Greenville	South Carolina	United States	29615
156	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
157	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29304
158	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
159	Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center	Nashville	Tennessee	United States	37232
160	Harrington Cancer Center	Amarillo	Texas	United States	79106
161	Brooke Army Medical Center	Fort Sam Houston	Texas	United States	78234
162	M.D. Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030
163	Wilford Hall Medical Center	Lackland Air Force Base	Texas	United States	78236
164	Cottonwood Hospital Medical Center	Murray	Utah	United States	84107
165	McKay-Dee Hospital Center	Ogden	Utah	United States	84403
166	Utah Valley Regional Medical Center - Provo	Provo	Utah	United States	84603
167	Dixie Regional Medical Center	Saint George	Utah	United States	84770
168	Utah Cancer Specialists at UCS Cancer Center	Salt Lake City	Utah	United States	84106
169	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah	United States	84112
170	LDS Hospital	Salt Lake City	Utah	United States	84143
171	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont	United States	05401
172	Danville Regional Medical Center	Danville	Virginia	United States	24541
173	Rappahannock General Hospital	Kilmarnock	Virginia	United States	22482
174	Naval Medical Center - Portsmouth	Portsmouth	Virginia	United States	23708-2197
175	Veterans Affairs Medical Center - Richmond	Richmond	Virginia	United States	23249
176	Massey Cancer Center at Virginia Commonwealth University	Richmond	Virginia	United States	23298-0037
177	Community Memorial Health Center	South Hill	Virginia	United States	23970-0090
178	North Star Lodge Cancer Center	Yakima	Washington	United States	98902
179	Washington Hematology - Oncology Specialists	Yakima	Washington	United States	98902
180	Schiffler Cancer Center at Wheeling Hospital	Wheeling	West Virginia	United States	26003
181	Green Bay Oncology, Limited at St. Vincent Hospital	Green Bay	Wisconsin	United States	54301-3526
182	St. Vincent Hospital	Green Bay	Wisconsin	United States	54301
183	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin	United States	54303
184	St. Mary's Hospital Medical Center	Green Bay	Wisconsin	United States	54303
185	Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
186	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin	United States	53792
187	Holy Family Memorial Medical Center	Manitowoc	Wisconsin	United States	54221
188	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin	United States	54143
189	Community Memorial Hospital	Menomonee Falls	Wisconsin	United States	53051
190	St. Mary's Cancer Center at Columbia St. Mary's Hospital - Milwaukee Campus	Milwaukee	Wisconsin	United States	53211
191	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin	United States	53226
192	Veterans Affairs Medical Center - Milwaukee (Zablocki)	Milwaukee	Wisconsin	United States	53295
193	Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin	United States	53066-3896
194	All Saints Cancer Center at All Saints Healthcare	Racine	Wisconsin	United States	53405
195	Waukesha Memorial Hospital Regional Cancer Center	Waukesha	Wisconsin	United States	53188

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Phuc Felix Nguyen-Tan, MD, CHUM Hospital Notre Dame

Study Documents (Full-Text)

None provided.

More Information

Publications

• Gillison ML, Zhang Q, Jordan R, Xiao W, Westra WH, Trotti A, Spencer S, Harris J, Chung CH, Ang KK. Tobacco smoking and increased risk of death and progression for patients with p16-positive and p16-negative oropharyngeal cancer. J Clin Oncol. 2012 Jun 10;30(17):2102-11. doi: 10.1200/JCO.2011.38.4099. Epub 2012 May 7.

• Responsible Party: Radiation Therapy Oncology Group
• ClinicalTrials.gov Identifier: NCT00047008
• Other Study ID Numbers: RTOG 0129; CDR0000257233; RTOG-H-0129
• First Posted: Jan 27, 2003
• Last Update Posted: Jun 14, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Radiation Therapy Oncology Group: stage III squamous cell carcinoma of the hypopharynx; stage III squamous cell carcinoma of the larynx; stage III squamous cell carcinoma of the lip and oral cavity; stage III squamous cell carcinoma of the oropharynx; stage IV squamous cell carcinoma of the hypopharynx; stage IV squamous cell carcinoma of the larynx; stage IV squamous cell carcinoma of the lip and oral cavity; stage IV squamous cell carcinoma of the oropharynx
• Additional relevant MeSH terms: Head and Neck Neoplasms; Cisplatin

Study Results

Participant Flow

Arm/Group Title	Standard Fractionation RT + Cisplatin	Accelerated Fractionation RT + Cisplatin
Arm/Group Description	Standard fractionation radiation therapy with concurrent cisplatin followed by conventional surgery for select patients.	Accelerated fractionation radiation therapy by concomitant boost with concurrent cisplatin followed by conventional surgery for select patients.
Period Title: Overall Study
STARTED	372	371
COMPLETED	361	360
NOT COMPLETED	11	11

Baseline Characteristics

Arm/Group Title	Standard Fractionation RT + Cisplatin	Accelerated Fractionation RT + Cisplatin	Total
Arm/Group Description	Standard fractionation radiation therapy with concurrent cisplatin followed by conventional surgery for select patients.	Accelerated fractionation radiation therapy by concomitant boost with concurrent cisplatin followed by conventional surgery for select patients.	Total of all reporting groups
Overall Participants	361	360	721
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	56	55	56
Sex: Female, Male (Count of Participants)
Female	52 14.4%	72 20%	124 17.2%
Male	309 85.6%	288 80%	597 82.8%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (3-year Rate)
Description	Time from randomization to death due to any cause or last known date alive. Median survival was not reached, therefore 3-year survival rates are reported.
Time Frame	From randomization to date of death or last follow-up. Analysis occurs after 309 deaths have been reported.

Outcome Measure Data

Analysis Population Description

Eligible patients who did not withdraw consent.

Arm/Group Title	Standard Fractionation RT + Cisplatin	Accelerated Fractionation RT + Cisplatin
Arm/Group Description	Standard fractionation radiation therapy with concurrent cisplatin followed by conventional surgery for select patients.	Accelerated fractionation radiation therapy by concomitant boost with concurrent cisplatin followed by conventional surgery for select patients.
Measure Participants	361	360
Number (95% Confidence Interval) [percentage of patients]	64.3	70.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Fractionation RT + Cisplatin, Accelerated Fractionation RT + Cisplatin
	Comments	A sample size of 684 analyzable patients provides 80% power to detect a relative reduction of 25% in the rate of death in the accelerated-fractionation radiotherapy group as compared with the standard-fractionation radiotherapy group, assuming a 2-year rate of overall survival of 45% in the standard-fractionation radiotherapy group, with the use of a one-sided log-rank test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.180
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95%; 0.719 to 1.128
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Local-regional Control
Description	From randomization to date of failure (local or regional persistence/relapse) or death or last follow-up. Analysis occurs after 309 deaths have been reported.
Time Frame	From randomization to date of failure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Disease-free Survival
Description	From randomization to date of failure (local or regional persistence/relapse, distant metastasis, secondary primary tumor or death) or last follow-up. Analysis occurs after 309 deaths have been reported.
Time Frame	From randomization to date of failure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Rate of Grade 3-5 Toxicity
Time Frame	From start of treatment to last follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Quality of Life
Time Frame	From randomization to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Correlation of Epidermal Growth Factor Receptor(EGFR) With Outcomes
Time Frame	From randomization to date of death or last follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Correlation of COX-2 With Outcomes
Time Frame	From randomization to date of death or last follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Adverse Event Reporting Description	Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Arm/Group Title	Standard Fractionation RT + Cisplatin		Accelerated Fractionation RT + Cisplatin
Arm/Group Description	Standard fractionation radiation therapy with concurrent cisplatin followed by conventional surgery for select patients.		Accelerated fractionation radiation therapy by concomitant boost with concurrent cisplatin followed by conventional surgery for select patients.
All Cause Mortality
	Standard Fractionation RT + Cisplatin		Accelerated Fractionation RT + Cisplatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Standard Fractionation RT + Cisplatin		Accelerated Fractionation RT + Cisplatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	293/361 (81.2%)		279/360 (77.5%)
Blood and lymphatic system disorders
Febrile neutropenia	15/361 (4.2%)		17/360 (4.7%)
Hemoglobin decreased	33/361 (9.1%)		24/360 (6.7%)
Lymphatics-Other	1/361 (0.3%)		0/360 (0%)
Packed red blood cell transfusion	7/361 (1.9%)		7/360 (1.9%)
Cardiac disorders
Circulatory or cardiac-Other	2/361 (0.6%)		0/360 (0%)
Myocardial ischaemia	1/361 (0.3%)		1/360 (0.3%)
Palpitations	1/361 (0.3%)		0/360 (0%)
Supraventricular arrhythmia NOS	1/361 (0.3%)		0/360 (0%)
Ear and labyrinth disorders
Hearing impaired	1/361 (0.3%)		0/360 (0%)
Endocrine disorders
Endocrine-Other	1/361 (0.3%)		0/360 (0%)
Gastrointestinal disorders
Diarrhea NOS	7/361 (1.9%)		1/360 (0.3%)
Dyspepsia	1/361 (0.3%)		0/360 (0%)
Dysphagia	82/361 (22.7%)		76/360 (21.1%)
Esophageal spasm	37/361 (10.2%)		31/360 (8.6%)
Esophagitis NOS	30/361 (8.3%)		48/360 (13.3%)
GI-other	3/361 (0.8%)		2/360 (0.6%)
Hematemesis	0/361 (0%)		2/360 (0.6%)
Ileus	1/361 (0.3%)		0/360 (0%)
Late RT Toxicity: Esophagus: NOS	28/361 (7.8%)		37/360 (10.3%)
Late RT Toxicity: Larynx: NOS	14/361 (3.9%)		18/360 (5%)
Late RT Toxicity: Mucous Membrane: NOS	3/361 (0.8%)		11/360 (3.1%)
Late RT Toxicity: Other: dysphagia	1/361 (0.3%)		0/360 (0%)
Late RT Toxicity: Other: tongue edema	1/361 (0.3%)		0/360 (0%)
Melaena	0/361 (0%)		1/360 (0.3%)
Nausea	72/361 (19.9%)		52/360 (14.4%)
Pancreatitis NOS	1/361 (0.3%)		1/360 (0.3%)
Proctalgia	0/361 (0%)		1/360 (0.3%)
Radiation mucositis	141/361 (39.1%)		117/360 (32.5%)
Salivary gland disorder NOS	1/361 (0.3%)		0/360 (0%)
Stomatitis	7/361 (1.9%)		2/360 (0.6%)
Stomatitis/pharyngitis for BMT	1/361 (0.3%)		0/360 (0%)
Tracheo-oesophageal fistula NOS	1/361 (0.3%)		0/360 (0%)
Vomiting NOS	66/361 (18.3%)		42/360 (11.7%)
General disorders
Fatigue	1/361 (0.3%)		3/360 (0.8%)
Late RT Toxicity: Other: pain	1/361 (0.3%)		0/360 (0%)
Pain due to radiation	30/361 (8.3%)		31/360 (8.6%)
Pain-other	9/361 (2.5%)		7/360 (1.9%)
Infections and infestations
Culture wound positive	0/361 (0%)		2/360 (0.6%)
Implant infection	2/361 (0.6%)		0/360 (0%)
Infection NOS	13/361 (3.6%)		8/360 (2.2%)
Infection with grade 3 or 4 neutropenia	5/361 (1.4%)		13/360 (3.6%)
Infection with unknown ANC	0/361 (0%)		2/360 (0.6%)
Infection, Other	4/361 (1.1%)		1/360 (0.3%)
Injury, poisoning and procedural complications
Dermatitis radiation NOS	29/361 (8%)		31/360 (8.6%)
Late RT Toxicity: Subcutaneous Tissue (within XRT field): NOS	2/361 (0.6%)		3/360 (0.8%)
Investigations
Blood alkaline phosphatase NOS increased	1/361 (0.3%)		0/360 (0%)
Blood creatine phosphokinase increased	1/361 (0.3%)		0/360 (0%)
Blood creatinine increased	16/361 (4.4%)		10/360 (2.8%)
Cardiac troponin T increased	1/361 (0.3%)		0/360 (0%)
Leukopenia NOS	14/361 (3.9%)		13/360 (3.6%)
Lymphopenia	0/361 (0%)		1/360 (0.3%)
Metabolic-Other	2/361 (0.6%)		0/360 (0%)
Neutropenia	17/361 (4.7%)		14/360 (3.9%)
Platelet count decreased	1/361 (0.3%)		0/360 (0%)
Metabolism and nutrition disorders
Anorexia	27/361 (7.5%)		22/360 (6.1%)
Blood magnesium decreased	4/361 (1.1%)		2/360 (0.6%)
Dehydration	76/361 (21.1%)		67/360 (18.6%)
Hypercalcemia	3/361 (0.8%)		1/360 (0.3%)
Hyperglycemia NOS	13/361 (3.6%)		4/360 (1.1%)
Hyperkalemia	7/361 (1.9%)		4/360 (1.1%)
Hypermagnesemia	4/361 (1.1%)		2/360 (0.6%)
Hypernatremia	3/361 (0.8%)		1/360 (0.3%)
Hyperuricemia	3/361 (0.8%)		5/360 (1.4%)
Hypocalcemia	4/361 (1.1%)		3/360 (0.8%)
Hypoglycaemia NOS	0/361 (0%)		1/360 (0.3%)
Hypokalemia	28/361 (7.8%)		17/360 (4.7%)
Hyponatremia	41/361 (11.4%)		33/360 (9.2%)
Hypophosphatemia	6/361 (1.7%)		4/360 (1.1%)
Musculoskeletal and connective tissue disorders
Joint, muscle, or bone-Other	0/361 (0%)		1/360 (0.3%)
Late RT Toxicity: Bone: NOS	14/361 (3.9%)		18/360 (5%)
Osteonecrosis	1/361 (0.3%)		0/360 (0%)
Nervous system disorders
Amnesia NEC	0/361 (0%)		1/360 (0.3%)
Cerebral ischaemia	0/361 (0%)		1/360 (0.3%)
Dizziness (exc vertigo)	4/361 (1.1%)		1/360 (0.3%)
Headache NOS	2/361 (0.6%)		2/360 (0.6%)
Hemorrhagic stroke	0/361 (0%)		1/360 (0.3%)
Late RT Toxicity: Brain: NOS	1/361 (0.3%)		1/360 (0.3%)
Late RT Toxicity: Spinal Cord: NOS	0/361 (0%)		1/360 (0.3%)
Neurologic-Other	1/361 (0.3%)		0/360 (0%)
Peripheral motor neuropathy	1/361 (0.3%)		1/360 (0.3%)
Peripheral sensory neuropathy	2/361 (0.6%)		0/360 (0%)
Syncope	5/361 (1.4%)		3/360 (0.8%)
Vasovagal attack	1/361 (0.3%)		1/360 (0.3%)
Renal and urinary disorders
Renal failure NOS	2/361 (0.6%)		1/360 (0.3%)
Renal/GU-Other	7/361 (1.9%)		3/360 (0.8%)
Urinary retention	1/361 (0.3%)		0/360 (0%)
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	0/361 (0%)		1/360 (0.3%)
Dysphonia	3/361 (0.8%)		0/360 (0%)
Dyspnea NOS	2/361 (0.6%)		4/360 (1.1%)
Hypoxia	0/361 (0%)		2/360 (0.6%)
Late RT Toxicity: Other: airway obstruction	0/361 (0%)		1/360 (0.3%)
Late RT Toxicity: Other: laryngeal hemorrhage	1/361 (0.3%)		0/360 (0%)
Late RT Toxicity: Other: pharyngeal bleed	0/361 (0%)		1/360 (0.3%)
Late RT Toxicity: Other: stenosis of airway	0/361 (0%)		1/360 (0.3%)
Late RT Toxicity: Other: upper airway obstruction	1/361 (0.3%)		0/360 (0%)
Pleural effusion	1/361 (0.3%)		0/360 (0%)
Pneumonitis NOS	4/361 (1.1%)		2/360 (0.6%)
Pulmonary-other	1/361 (0.3%)		3/360 (0.8%)
Vascular disorders
Hemorrhage-Other	1/361 (0.3%)		2/360 (0.6%)
Hypertension NOS	1/361 (0.3%)		0/360 (0%)
Hypotension NOS	6/361 (1.7%)		7/360 (1.9%)
Late RT Toxicity: Other: arteritis	0/361 (0%)		1/360 (0.3%)
Thrombosis NOS	2/361 (0.6%)		1/360 (0.3%)
Visceral arterial ischaemia	0/361 (0%)		1/360 (0.3%)
Other (Not Including Serious) Adverse Events
	Standard Fractionation RT + Cisplatin		Accelerated Fractionation RT + Cisplatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	360/361 (99.7%)		356/360 (98.9%)
Blood and lymphatic system disorders
Hemoglobin decreased	325/361 (90%)		301/360 (83.6%)
Ear and labyrinth disorders
Hearing impaired	63/361 (17.5%)		35/360 (9.7%)
Hearing-Other	52/361 (14.4%)		53/360 (14.7%)
Gastrointestinal disorders
Constipation	73/361 (20.2%)		54/360 (15%)
Diarrhea NOS	37/361 (10.2%)		27/360 (7.5%)
Dry mouth	184/361 (51%)		156/360 (43.3%)
Dysphagia	112/361 (31%)		94/360 (26.1%)
Esophageal spasm	58/361 (16.1%)		52/360 (14.4%)
Esophagitis NOS	118/361 (32.7%)		101/360 (28.1%)
Late RT Toxicity: Esophagus: NOS	145/361 (40.2%)		152/360 (42.2%)
Late RT Toxicity: Larynx: NOS	161/361 (44.6%)		132/360 (36.7%)
Late RT Toxicity: Mucous Membrane: NOS	143/361 (39.6%)		147/360 (40.8%)
Late RT Toxicity: Salivary Gland (xerostomia, taste impairment)	270/361 (74.8%)		271/360 (75.3%)
Nausea	210/361 (58.2%)		197/360 (54.7%)
Radiation mucositis	282/361 (78.1%)		267/360 (74.2%)
Salivary gland disorder NOS	120/361 (33.2%)		116/360 (32.2%)
Stomatitis	29/361 (8%)		19/360 (5.3%)
Vomiting NOS	140/361 (38.8%)		131/360 (36.4%)
General disorders
Edema NOS	14/361 (3.9%)		19/360 (5.3%)
Fatigue	212/361 (58.7%)		198/360 (55%)
Late RT Toxicity: Other: NOS	173/361 (47.9%)		171/360 (47.5%)
Pain due to radiation	144/361 (39.9%)		135/360 (37.5%)
Pain-other	46/361 (12.7%)		41/360 (11.4%)
Pyrexia	31/361 (8.6%)		33/360 (9.2%)
Infections and infestations
Infection NOS	21/361 (5.8%)		30/360 (8.3%)
Infection, Other	20/361 (5.5%)		14/360 (3.9%)
Injury, poisoning and procedural complications
Dermatitis radiation NOS	236/361 (65.4%)		213/360 (59.2%)
Late RT Toxicity: Skin(within RT field): NOS	145/361 (40.2%)		145/360 (40.3%)
Late RT Toxicity: Subcutaneous Tissue (within XRT field): NOS	159/361 (44%)		171/360 (47.5%)
Investigations
Alanine aminotransferase increased	32/361 (8.9%)		34/360 (9.4%)
Aspartate aminotransferase increased	27/361 (7.5%)		29/360 (8.1%)
Blood alkaline phosphatase NOS increased	27/361 (7.5%)		13/360 (3.6%)
Blood creatinine increased	122/361 (33.8%)		85/360 (23.6%)
Leukopenia NOS	302/361 (83.7%)		254/360 (70.6%)
Lymphopenia	48/361 (13.3%)		42/360 (11.7%)
Metabolic-Other	26/361 (7.2%)		28/360 (7.8%)
Neutropenia	227/361 (62.9%)		176/360 (48.9%)
Platelet count decreased	103/361 (28.5%)		87/360 (24.2%)
Weight decreased	171/361 (47.4%)		153/360 (42.5%)
Metabolism and nutrition disorders
Anorexia	95/361 (26.3%)		72/360 (20%)
Blood albumin decreased	79/361 (21.9%)		64/360 (17.8%)
Blood magnesium decreased	96/361 (26.6%)		73/360 (20.3%)
Dehydration	166/361 (46%)		108/360 (30%)
Hyperglycemia NOS	67/361 (18.6%)		57/360 (15.8%)
Hyperkalemia	47/361 (13%)		24/360 (6.7%)
Hypocalcemia	71/361 (19.7%)		51/360 (14.2%)
Hypokalemia	84/361 (23.3%)		67/360 (18.6%)
Hyponatremia	126/361 (34.9%)		92/360 (25.6%)
Musculoskeletal and connective tissue disorders
Joint, muscle, or bone-Other	20/361 (5.5%)		18/360 (5%)
Late RT Toxicity: Bone: NOS	24/361 (6.6%)		29/360 (8.1%)
Late RT Toxicity: Joint: NOS	48/361 (13.3%)		59/360 (16.4%)
Nervous system disorders
Late RT Toxicity: Spinal Cord: NOS	15/361 (4.2%)		20/360 (5.6%)
Peripheral sensory neuropathy	55/361 (15.2%)		29/360 (8.1%)
Taste disturbance	114/361 (31.6%)		117/360 (32.5%)
Psychiatric disorders
Depression NEC	21/361 (5.8%)		20/360 (5.6%)
Insomnia NEC	21/361 (5.8%)		17/360 (4.7%)
Renal and urinary disorders
Renal/GU-Other	40/361 (11.1%)		23/360 (6.4%)
Respiratory, thoracic and mediastinal disorders
Cough	28/361 (7.8%)		33/360 (9.2%)
Dysphonia	75/361 (20.8%)		55/360 (15.3%)
Skin and subcutaneous tissue disorders
Alopecia	25/361 (6.9%)		15/360 (4.2%)
Dermatitis exfoliative NOS	20/361 (5.5%)		21/360 (5.8%)
Skin-Other	27/361 (7.5%)		12/360 (3.3%)

Limitations/Caveats

[Not Specified]

More Information

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