Adjuvant Cetuximab and Chemoradiotherapy Using Either Cisplatin or Docetaxel in Treating Patients With Resected Stage III or Stage IV Squamous Cell Carcinoma or Lymphoepithelioma of the Head and Neck

• Sponsor: Radiation Therapy Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00084318
• Collaborator: National Cancer Institute (NCI) (NIH), NRG Oncology (Other)
• Enrollment: 238
• Locations: 160
• Arms: 2
• Duration (Months): 152
• Patients Per Site: 1.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as cisplatin and docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Cisplatin and docetaxel may make the tumor cells more sensitive to radiation therapy. Combining a monoclonal antibody with chemoradiotherapy and giving them after surgery may kill any remaining tumor cells.

PURPOSE: This randomized phase II trial is studying adjuvant cetuximab given together with chemoradiotherapy using cisplatin to see how well it works compared to adjuvant cetuximab given together with chemoradiotherapy using docetaxel in treating patients with resected stage III or stage IV squamous cell carcinoma (cancer) or lymphoepithelioma of the head and neck.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer	Biological: cetuximab; Drug: cisplatin; Drug: docetaxel; Radiation: radiation therapy	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Compare disease-free survival of patients with resected stage III or IV squamous cell carcinoma or lymphoepithelioma of the head and neck treated with adjuvant cetuximab in combination with chemoradiotherapy comprising docetaxel vs cisplatin.

Secondary

• Compare the safety and efficacy of these regimens in these patients.

• Compare locoregional control and overall survival rates in patients treated with these regimens.

• Correlate epidermal growth factor receptor (total and phosphorylated), pMAPK, pAKT, Stat-3, Ki-67, cyclo-oxygenase-2, and cyclin B1 expression with outcome in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to Zubrod performance status (0 vs 1), risk category (positive margins vs high risk [i.e., ≥ 2 positive nodes or extracapsular nodal extension]) and use of intensity-modulated radiotherapy (no vs yes). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive cetuximab IV over 2 hours on day 1 (week 1). Patients then receive cetuximab IV over 1 hour and cisplatin IV over 1 hour before radiotherapy on days 8, 15, 22, 29, 36, and 43 (weeks 2-7). Patients undergo radiotherapy once daily, 5 days a week, beginning on day 8 for a total of 6 weeks (weeks 2-7).

• Arm II: Patients receive cetuximab and undergo radiotherapy as in arm I. Patients also receive docetaxel IV over 30 minutes before radiotherapy on days 8, 15, 22, 29, 36, and 43 (weeks 2-7).

Treatment in both arms continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 4 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 230 patients (115 per treatment arm) will be accrued for this study within approximately 29 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 238 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Randomized Trial Of Surgery Followed By Chemoradiotherapy Plus Cetuximab For Advanced Squamous Cell Carcinoma Of The Head and Neck
• Study Start Date: Apr 1, 2004
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RT + cisplatin + cetuximab Loading dose of cetuximab followed by radiation therapy with weekly cisplatin and cetuximab.	Biological: cetuximab; 400 mg/m^2 intravenously over 120 minutes on day 1 (week 1) followed by 250 mg/m^2 intravenously over 60 minutes in weeks 2 through 7.; Drug: cisplatin; 30 mg/m^2 intravenously infused over over 60 minutes in weeks 2 through 7.; Radiation: radiation therapy; 60 Gy (2 Gy once a day, 5 times a week)
Experimental: RT + docetaxel + cetuximab Loading dose of cetuximab followed by radiation therapy (RT) with weekly docetaxel and cetuximab.	Biological: cetuximab; 400 mg/m^2 intravenously over 120 minutes on day 1 (week 1) followed by 250 mg/m^2 intravenously over 60 minutes in weeks 2 through 7.; Drug: docetaxel; 15 mg/m^2 intravenously infused over 30 minutes in weeks 2 through 7.; Radiation: radiation therapy; 60 Gy (2 Gy once a day, 5 times a week)

Outcome Measures

Primary Outcome Measures

1. Disease-free Survival [From randomization to 2 years]

   Two-year rates are shown (Kaplan-Meier estimates). Disease-free survival is defined as the time from randomization to local, regional, or distant progression, second primary, or death (event) or last follow-up (censored). Response criteria as follows: No evidence of disease (NED): All patients must have no measurable tumor following surgery; Local-Regional Relapse: Recurrent cancer in the tumor bed and/or neck not clearly attributable to a second primary neoplasm; biopsy confirmation is necessary; Distant Relapse: Clear evidence of distant metastases (lung, bone, brain, etc.); Biopsy is recommended where possible. A solitary lung mass/nodule is considered a second primary neoplasm unless proven otherwise.

Secondary Outcome Measures

1. Overall Survival [From randomization to 2 years]

   Two-year rates are shown (Kaplan-Meier estimates). Overall survival is defined as the time from randomization to death (event) or last follow-up (censored).

2. Treatment Tolerance [From start of treatment to end of treatment (protocol treatment lasts seven weeks).]

   Tolerability was defined as having received 90% of the radiation dose, 95% of the cetuximab loading dose, and at least 4 weeks of cetuximab and cisplatin or docetaxel at doses 95% of the protocol prescription. The percentage of patients determined to be tolerant of treatment are shown.

3. Frequency of Toxicity (Grade 5 and Acute Non-hematologic Grade 4) [From start of treatment to last follow-up. Analysis occurs at the time of the primary analysis.]

   Each regimen was monitored for excessive acute toxicity (defined as nonhematologic grade 4 toxicity within 90 days of the start of radiation or any grade 5 toxicity). The target rate was based on the observed rate from RTOG-9501/NCT00002670 of 15%. The unacceptable rate was >30%. [RTOG = Radiation Therapy Oncology Group]

4. Frequency of Other Acute and Late Toxicity [From start of treatment to last follow-up. Analysis occurs at the time of the primary endpoint analysis.]

   Maximum grade toxicity that is definitely, probably, or possibly related to protocol treatment.

5. Local-regional Control [From randomization to 2 years]

   Two-year rate is shown (cumulative incidence estimate). Local-regional failure is defined as the time from randomization to local-regional recurrence (event), death (competing risk), or last follow-up (censored).

6. Correlation of EGFR (Total and Phosphorylated) pMAPK, pAKT, Stat-3, KI-67, COX-2, and Cyclin B1 Expression With Local-regional Control, and Overall and Disease-free Survival [From randomization to two years]

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 head and neck meeting the following criteria:

• Site of tumor origin in the oral cavity, oropharynx, larynx, or hypopharynx (excluding lip, nasopharynx, or sinuses)

• Gross total resection must be completed within 7 weeks of randomization, with pathology demonstrating one or more of the following risk factors:

• Histologic extracapsular nodal extension

• Histologic involvement of ≥ 2 regional lymph nodes

• Invasive cancer seen on microscopic evaluation of the resection margin, with no evidence of gross tumor residual.

• Tonsillar cancer patients who undergo transoral excision of all gross tumor are eligible provided extracapsular nodal extension or involvement of ≥ 2 regional lymph nodes is histologically confirmed

• American Joint Committee on Cancer (AJCC) pathological stage III or IV

• No evidence of distant metastases

• No synchronous or concurrent head and neck primary tumors

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 2,000/mm^3

• Platelet count ≥ 100,000/mm^3

• Hemoglobin > 8.0 g/dL

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT), and alkaline phosphatase meeting 1 of the following parameters:

• Alkaline phosphatase ≤ ULN AND AST or ALT ≤ 5 times ULN

• Alkaline phosphatase ≤ 2.5 times ULN AND AST or ALT ≤ 1.5 times ULN

• Alkaline phosphatase ≤ 5 times ULN AND AST or ALT ≤ ULN

Renal

• Creatinine ≤ 1.5 mg/dL

Cardiovascular

• No unstable angina

• No uncontrolled hypertension

• No myocardial infarction within the past 6 months (unless successfully treated with coronary artery bypass surgery or percutaneous transluminal coronary angioplasty)

• No uncontrolled arrhythmia

• No congestive heart failure

• No more than 2 heart-related hospitalizations within the past year

• No other active cardiac disease

Pulmonary

• No more than 2 hospitalizations for chronic obstructive pulmonary disease within the past year

Neurologic

• No pre-existing peripheral neuropathy ≥ grade 2

• No uncontrolled seizure disorder

• No active neurological disease

Other

• No prior severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80

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

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 3 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior anti-epidermal growth factor receptor antibody therapy

Chemotherapy

• More than 3 years since prior cytotoxic chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior head and neck radiotherapy

Surgery

• See Disease Characteristics

Other

• No prior tyrosine kinase inhibitor therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama	United States	35294
2	Mobile Infirmary Medical Center	Mobile	Alabama	United States	36652-2144
3	Arizona Oncology Services Foundation	Phoenix	Arizona	United States	85013
4	Virginia G. Piper Cancer Center at Scottsdale Healthcare - Osborn	Scottsdale	Arizona	United States	85251
5	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259-5499
6	Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea	Scottsdale	Arizona	United States	85260
7	Auburn Radiation Oncology	Auburn	California	United States	95603
8	Providence Saint Joseph Medical Center - Burbank	Burbank	California	United States	91505
9	Radiation Oncology Centers - Cameron Park	Cameron Park	California	United States	95682
10	Mercy Cancer Center at Mercy San Juan Medical Center	Carmichael	California	United States	95608
11	Loma Linda University Cancer Institute at Loma Linda University Medical Center	Loma Linda	California	United States	92354
12	Providence Holy Cross Cancer Center	Mission Hills	California	United States	91346-9600
13	CCOP - Bay Area Tumor Institute	Oakland	California	United States	94609
14	Radiation Oncology Center - Roseville	Roseville	California	United States	95661
15	Radiological Associates of Sacramento Medical Group, Incorporated	Sacramento	California	United States	95815
16	University of California Davis Cancer Center	Sacramento	California	United States	95817
17	Mercy General Hospital	Sacramento	California	United States	95819
18	Torrance Memorial Medical Center	Torrance	California	United States	90509
19	Solano Radiation Oncology Center	Vacaville	California	United States	95687
20	University of Colorado Cancer Center at University of Colorado Health Sciences Center	Aurora	Colorado	United States	80045
21	Hospital of Saint Raphael	New Haven	Connecticut	United States	06511
22	CCOP - Christiana Care Health Services	Newark	Delaware	United States	19713
23	Lynn Regional Cancer Center at Boca Raton Community Hospital - Main Center	Boca Raton	Florida	United States	33486
24	Michael & Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital	Fort Lauderdale	Florida	United States	33308
25	Baptist Cancer Institute - Jacksonville	Jacksonville	Florida	United States	32207
26	Mayo Clinic - Jacksonville	Jacksonville	Florida	United States	32224
27	Ella Milbank Foshay Cancer Center at Jupiter Medical Center	Jupiter	Florida	United States	33458
28	CCOP - Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
29	University of Miami Sylvester Comprehensive Cancer Center	Miami	Florida	United States	33136
30	M.D. Anderson Cancer Center Orlando	Orlando	Florida	United States	32806
31	Tallahassee Memorial Hospital	Tallahassee	Florida	United States	32308
32	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida	Tampa	Florida	United States	33612-9497
33	John B. Amos Cancer Center	Columbus	Georgia	United States	31904
34	Northeast Georgia Medical Center	Gainesville	Georgia	United States	30501
35	Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia	United States	31403-3089
36	Saint Anthony's Hospital at Saint Anthony's Health Center	Alton	Illinois	United States	62002
37	Ingalls Cancer Care Center at Ingalls Memorial Hospital	Harvey	Illinois	United States	60426
38	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois	United States	60153
39	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
40	Cancer Institute at St. John's Hospital	Springfield	Illinois	United States	62702
41	Elkhart General Hospital	Elkhart	Indiana	United States	46515
42	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana	United States	46350
43	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
44	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
45	Wendt Regional Cancer Center at Finley Hospital	Dubuque	Iowa	United States	52001
46	John D. Cronin Cancer Center	Lexington	Kentucky	United States	40504
47	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky	United States	40536-0293
48	Tulane Cancer Center	Alexandria	Louisiana	United States	71315-3198
49	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
50	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
51	Dana-Farber/Brigham and Women's Cancer Center	Boston	Massachusetts	United States	02115
52	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
53	Cancer Research Center at Boston Medical Center	Boston	Massachusetts	United States	02118
54	Hudner Oncology Center at Saint Anne's Hospital - Fall River	Fall River	Massachusetts	United States	02721
55	St. Joseph Mercy Cancer Center at St. Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106-0995
56	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan	United States	48202
57	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
58	Hurley Medical Center	Flint	Michigan	United States	48503
59	CCOP - Grand Rapids	Grand Rapids	Michigan	United States	49503
60	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan	United States	49503
61	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
62	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007-3731
63	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
64	Upper Michigan Cancer Center at Marquette General Hospital	Marquette	Michigan	United States	49855
65	Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph	Saint Joseph	Michigan	United States	49085
66	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
67	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
68	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
69	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
70	Virginia Piper Cancer Institute at Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55407
71	University of Minnesota Medical Center & Children's Hospital - Fairview	Minneapolis	Minnesota	United States	55455
72	Hubert H. Humphrey Cancer Center at North Memorial Medical Center	Robbinsdale	Minnesota	United States	55422-2900
73	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
74	CentraCare Clinic - River Campus	Saint Cloud	Minnesota	United States	56303
75	Coborn Cancer Center	Saint Cloud	Minnesota	United States	56303
76	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
77	Park Nicollet Health Services	Saint Louis Park	Minnesota	United States	55416
78	United Hospital	Saint Paul	Minnesota	United States	55102
79	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
80	Regional Cancer Center at Singing River Hospital	Pascagoula	Mississippi	United States	39581
81	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63701
82	Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital	Cape Girardeau	Missouri	United States	63701
83	CCOP - Kansas City	Kansas City	Missouri	United States	64131
84	Siteman Cancer Center at Barnes-Jewish Hospital	Saint Louis	Missouri	United States	63110
85	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri	United States	63141
86	David C. Pratt Cancer Center at St. John's Mercy	Saint Louis	Missouri	United States	63141
87	St. John's Regional Health Center	Springfield	Missouri	United States	65804
88	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri	United States	65807
89	Good Samaritan Cancer Center at Good Samaritan Hospital	Kearney	Nebraska	United States	68848-1990
90	Methodist Cancer Center at Methodist Hospital - Omaha	Omaha	Nebraska	United States	68114
91	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756-0002
92	Cancer Institute of New Jersey at Cooper University Hospital - Camden	Camden	New Jersey	United States	08103
93	Veterans Affairs Medical Center - East Orange	East Orange	New Jersey	United States	07018-1095
94	Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton	Marlton	New Jersey	United States	08053
95	Saint Peter's University Hospital	New Brunswick	New Jersey	United States	08903
96	J. Phillip Citta Regional Cancer Center at Community Medical Center	Toms River	New Jersey	United States	08755
97	Fox Chase Virtua Health Cancer Program at Virtua West Jersey	Voorhees	New Jersey	United States	08043
98	Long Island College Hospital	Brooklyn	New York	United States	11201
99	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
100	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
101	SUNY Upstate Medical University Hospital	Syracuse	New York	United States	13210
102	Mission Hospitals - Memorial Campus	Asheville	North Carolina	United States	28801
103	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina	United States	28232-2861
104	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina	United States	27534
105	Leo W. Jenkins Cancer Center at ECU Medical School	Greenville	North Carolina	United States	27835-6028
106	Iredell Memorial Hospital	Statesville	North Carolina	United States	28677
107	Forsyth Regional Cancer Center at Forsyth Medical Center	Winston-Salem	North Carolina	United States	27103
108	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio	United States	44307
109	Akron City Hospital	Akron	Ohio	United States	44309-2090
110	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio	United States	45267
111	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University	Columbus	Ohio	United States	43210-1240
112	Hillcrest Cancer Center at Hillcrest Hospital	Mayfield Heights	Ohio	United States	44124
113	Oregon Health & Science University Cancer Institute	Portland	Oregon	United States	97239-3098
114	Rosenfeld Cancer Center at Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
115	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania	United States	19010
116	Dale and Frances Hughes Cancer Center at Pocono Medical Center	East Stroudsburg	Pennsylvania	United States	18301
117	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
118	Cancer Center of Paoli Memorial Hospital	Paoli	Pennsylvania	United States	19301-1792
119	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania	United States	19107-5541
120	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania	United States	19111-2497
121	Mercy Cancer Institute at Mercy Hospital	Pittsburgh	Pennsylvania	United States	15219
122	Reading Hospital and Medical Center	Reading	Pennsylvania	United States	19612-6052
123	Guthrie Cancer Center at Guthrie Clinic Sayre	Sayre	Pennsylvania	United States	18840
124	Mount Nittany Medical Center	State College	Pennsylvania	United States	16803
125	CCOP - MainLine Health	Wynnewood	Pennsylvania	United States	19096
126	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania	United States	19096
127	York Cancer Center at Apple Hill Medical Center	York	Pennsylvania	United States	17405
128	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina	United States	29425
129	Bon Secours St. Francis Health System	Greenville	South Carolina	United States	29601
130	CCOP - Greenville	Greenville	South Carolina	United States	29615
131	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
132	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
133	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
134	Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center	Kingsport	Tennessee	United States	37662
135	Thompson Cancer Survival Center	Knoxville	Tennessee	United States	37916
136	M.D. Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030-4009
137	CCOP - Scott and White Hospital	Temple	Texas	United States	76508
138	Cottonwood Hospital Medical Center	Murray	Utah	United States	84107
139	McKay-Dee Hospital Center	Ogden	Utah	United States	84403
140	Utah Valley Regional Medical Center - Provo	Provo	Utah	United States	84604
141	Dixie Regional Medical Center - East Campus	Saint George	Utah	United States	84770
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	Latter Day Saints Hospital	Salt Lake City	Utah	United States	84143
145	Danville Regional Medical Center	Danville	Virginia	United States	24541
146	Veterans Affairs Medical Center - Richmond	Richmond	Virginia	United States	23249
147	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia	United States	23298-0037
148	St. Joseph Cancer Center	Bellingham	Washington	United States	98225
149	CCOP - Virginia Mason Research Center	Seattle	Washington	United States	98101
150	University Cancer Center at University of Washington Medical Center	Seattle	Washington	United States	98195-6043
151	Schiffler Cancer Center at Wheeling Hospital	Wheeling	West Virginia	United States	26003
152	Green Bay Oncology, Limited at St. Vincent Hospital	Green Bay	Wisconsin	United States	54301-3526
153	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin	United States	54303
154	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin	United States	54303
155	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
156	Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
157	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin	United States	53792-6164
158	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin	United States	54143
159	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin	United States	53226
160	All Saints Cancer Center at All Saints Healthcare	Racine	Wisconsin	United States	53405

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Paul M. Harari, MD, University of Wisconsin, Madison
• Study Chair: Merrill S. Kies, MD, M.D. Anderson Cancer Center
• Study Chair: Jeffrey N. Myers, MD, PhD, FACS, 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: NCT00084318
• Other Study ID Numbers: RTOG-0234; CDR0000360850; NCT00414674
• First Posted: Jun 11, 2004
• Last Update Posted: Dec 12, 2018
• Last Verified: Dec 1, 2016

• Keywords provided by Radiation Therapy Oncology Group: stage III squamous cell carcinoma of the hypopharynx; stage IV squamous cell carcinoma of the hypopharynx; stage III squamous cell carcinoma of the oropharynx; stage IV squamous cell carcinoma of the oropharynx; stage III squamous cell carcinoma of the larynx; stage IV squamous cell carcinoma of the larynx; stage III lymphoepithelioma of the oropharynx; stage IV lymphoepithelioma of the oropharynx
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Docetaxel; Cetuximab

Study Results

Participant Flow

Arm/Group Title	RT + Cisplatin + Cetuximab	RT + Docetaxel + Cetuximab
Arm/Group Description	Loading dose of cetuximab followed by radiation therapy with weekly cisplatin and cetuximab.	Loading dose of cetuximab followed by radiation therapy (RT) with weekly docetaxel and cetuximab.
Period Title: Overall Study
STARTED	119	119
COMPLETED	97	106
NOT COMPLETED	22	13

Baseline Characteristics

Arm/Group Title	RT + Cisplatin + Cetuximab	RT + Docetaxel + Cetuximab	Total
Arm/Group Description	Loading dose of cetuximab followed by radiation therapy with weekly cisplatin and cetuximab.	Loading dose of cetuximab followed by radiation therapy (RT) with weekly docetaxel and cetuximab.	Total of all reporting groups
Overall Participants	97	106	203
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	57	55	56
Sex: Female, Male (Count of Participants)
Female	20 20.6%	32 30.2%	52 25.6%
Male	77 79.4%	74 69.8%	151 74.4%

Outcome Measures

1. Primary Outcome

Title	Disease-free Survival
Description	Two-year rates are shown (Kaplan-Meier estimates). Disease-free survival is defined as the time from randomization to local, regional, or distant progression, second primary, or death (event) or last follow-up (censored). Response criteria as follows: No evidence of disease (NED): All patients must have no measurable tumor following surgery; Local-Regional Relapse: Recurrent cancer in the tumor bed and/or neck not clearly attributable to a second primary neoplasm; biopsy confirmation is necessary; Distant Relapse: Clear evidence of distant metastases (lung, bone, brain, etc.); Biopsy is recommended where possible. A solitary lung mass/nodule is considered a second primary neoplasm unless proven otherwise.
Time Frame	From randomization to 2 years

Outcome Measure Data

Analysis Population Description

Eligible patients who started protocol treatment and did not withdraw consent.

Arm/Group Title	RT + Cisplatin + Cetuximab	RT + Docetaxel + Cetuximab
Arm/Group Description	Loading dose of cetuximab followed by radiation therapy with weekly cisplatin and cetuximab.	Loading dose of cetuximab followed by radiation therapy (RT) with weekly docetaxel and cetuximab.
Measure Participants	97	106
Number (95% Confidence Interval) [percentage of participants]	57.3 59.1%	65.9 62.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RT + Cisplatin + Cetuximab
	Comments	Using the method of Dixon and Simon, 104 analyzable patients per arm were needed to detect a ≥ 33 reduction in the hazard rate for disease-free survival compared to historical control data (the chemoradiation arm of study RTOG-9501/NCT00002670) with 80% power and one-sided log-rank test at the 0.05 level. Two-year rates were estimated by the Kaplan-Meier method. [RTOG = Radiation Therapy Oncology Group]
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments
	Method	Log Rank
	Comments	Historical control data (RTOG-9501/NCT00002670): n=202, two-year disease-free survival rate of 54.8% (47.9% to 61.7%).
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.76
	Confidence Interval	(2-Sided) 95%; 0.54 to 1.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	RT + Docetaxel + Cetuximab
	Comments	Using the method of Dixon and Simon, 104 analyzable patients per arm were needed to detect a ≥ 33 reduction in the hazard rate for disease-free survival compared to historical control data (the chemoradiation arm of study RTOG-9501/NCT00002670) with 80% power and one-sided log-rank test at the 0.05 level. Two-year rates were estimated by the Kaplan-Meier method.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.01
	Comments
	Method	Log Rank
	Comments	Historical control data (RTOG-9501/NCT00002670): n=202, two-year disease-free survival rate of 54.8% (47.9% to 61.7%).
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.69
	Confidence Interval	(2-Sided) 95%; 0.50 to 0.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Overall Survival
Description	Two-year rates are shown (Kaplan-Meier estimates). Overall survival is defined as the time from randomization to death (event) or last follow-up (censored).
Time Frame	From randomization to 2 years

Outcome Measure Data

Analysis Population Description

Eligible patients who started protocol treatment and did not withdraw consent

Arm/Group Title	RT + Cisplatin + Cetuximab	RT + Docetaxel + Cetuximab
Arm/Group Description	Loading dose of cetuximab followed by radiation therapy with weekly cisplatin and cetuximab.	Loading dose of cetuximab followed by radiation therapy (RT) with weekly docetaxel and cetuximab.
Measure Participants	97	106
Number (95% Confidence Interval) [percentage of participants]	68.8 70.9%	79.2 74.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RT + Cisplatin + Cetuximab
	Comments	Two-year rates were estimated by the Kaplan-Meier method. RTOG 0234 results were compared to historical control data (the chemoradiation arm of study RTOG-9501/NCT00002670) by 1-sided log-rank test. Hazard ratios were estimated by Cox model. [RTOG = Radiation Therapy Oncology Group]
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments
	Method	Log Rank
	Comments	Historical control data (RTOG-9501/NCT00002670): n=202, two-year survival rate of 64.7% (58.1% to 71.3%).
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.72
	Confidence Interval	(2-Sided) 95%; 0.5 to 1.03
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference arm = historical control

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	RT + Docetaxel + Cetuximab
	Comments	Two-year rates were estimated by the Kaplan-Meier method. RTOG 0234 results were compared to historical control data (the chemoradiation arm of study RTOG-9501/NCT00002670) by 1-sided log-rank test. Hazard ratios were estimated by Cox model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Log Rank
	Comments	Historical control data (RTOG-9501/NCT00002670): n=202, two-year survival rate of 64.7% (58.1% to 71.3%).
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.56
	Confidence Interval	(2-Sided) 95%; 0.39 to 0.82
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference arm = historical control

3. Secondary Outcome

Title	Treatment Tolerance
Description	Tolerability was defined as having received 90% of the radiation dose, 95% of the cetuximab loading dose, and at least 4 weeks of cetuximab and cisplatin or docetaxel at doses 95% of the protocol prescription. The percentage of patients determined to be tolerant of treatment are shown.
Time Frame	From start of treatment to end of treatment (protocol treatment lasts seven weeks).

Outcome Measure Data

Analysis Population Description

Eligible patients who started protocol treatment and did not withdraw consent

Arm/Group Title	RT+Cisplatin+Cetuximab	RT+Docetaxel+Cetuximab
Arm/Group Description	Loading dose of cetuximab followed by radiation therapy with weekly cisplatin and cetuximab.	Loading dose of cetuximab followed by radiation therapy (RT) with weekly docetaxel and cetuximab.
Measure Participants	97	106
Number (95% Confidence Interval) [percentage of participants]	80.4 82.9%	84.9 80.1%

4. Secondary Outcome

Title	Frequency of Toxicity (Grade 5 and Acute Non-hematologic Grade 4)
Description	Each regimen was monitored for excessive acute toxicity (defined as nonhematologic grade 4 toxicity within 90 days of the start of radiation or any grade 5 toxicity). The target rate was based on the observed rate from RTOG-9501/NCT00002670 of 15%. The unacceptable rate was >30%. [RTOG = Radiation Therapy Oncology Group]
Time Frame	From start of treatment to last follow-up. Analysis occurs at the time of the primary analysis.

Outcome Measure Data

Analysis Population Description

Eligible patients who started protocol treatment and did not withdraw consent

Arm/Group Title	RT+Cisplatin+Cetuximab	RT+Docetaxel+Cetuximab
Arm/Group Description	Loading dose of cetuximab followed by radiation therapy with weekly cisplatin and cetuximab.	Loading dose of cetuximab followed by radiation therapy (RT) with weekly docetaxel and cetuximab.
Measure Participants	97	106
Number (95% Confidence Interval) [percentage of participants]	9.3 9.6%	12.3 11.6%

5. Secondary Outcome

Title	Frequency of Other Acute and Late Toxicity
Description	Maximum grade toxicity that is definitely, probably, or possibly related to protocol treatment.
Time Frame	From start of treatment to last follow-up. Analysis occurs at the time of the primary endpoint analysis.

Outcome Measure Data

Analysis Population Description

Eligible patients who started protocol treatment and did not withdraw consent

Arm/Group Title	RT+Cisplatin+Cetuximab	RT+Docetaxel+Cetuximab
Arm/Group Description	Loading dose of cetuximab followed by radiation therapy with weekly cisplatin and cetuximab.	Loading dose of cetuximab followed by radiation therapy (RT) with weekly docetaxel and cetuximab.
Measure Participants	97	106
Grade 1	1.0 1%	0.0 0%
Grade 2	10.3 10.6%	9.4 8.9%
Grade 3	74.2 76.5%	73.6 69.4%
Grade 4	14.4 14.8%	16.0 15.1%
Grade 5	0.0 0%	0.9 0.8%

6. Secondary Outcome

Title	Local-regional Control
Description	Two-year rate is shown (cumulative incidence estimate). Local-regional failure is defined as the time from randomization to local-regional recurrence (event), death (competing risk), or last follow-up (censored).
Time Frame	From randomization to 2 years

Outcome Measure Data

Analysis Population Description

Eligible patients who started protocol treatment and did not withdraw consent.

Arm/Group Title	RT + Cisplatin + Cetuximab	RT + Docetaxel + Cetuximab
Arm/Group Description	Loading dose of cetuximab followed by radiation therapy with weekly cisplatin and cetuximab.	Loading dose of cetuximab followed by radiation therapy (RT) with weekly docetaxel and cetuximab.
Measure Participants	97	106
Number (95% Confidence Interval) [percentage of participants]	19.8 20.4%	18.9 17.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RT + Cisplatin + Cetuximab
	Comments	Two-year failure rates were estimated by the cumulative incidence method. RTOG 0234 results were compared to historical control data (the chemoradiation arm of study RTOG-9501/NCT00002670) by 1-sided Gray's test. Hazard ratios were estimated by Cox model. [RTOG = Radiation Therapy Oncology Group]
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.66
	Comments
	Method	Gray's test
	Comments	Historical control data (RTOG-9501/NCT00002670): n=202, two-year failure rate of 19.9% (12.2% to 27.5%)
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 95%; 0.63 to 1.76
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference arm = historical control

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	RT + Docetaxel + Cetuximab
	Comments	Two-year failure rates were estimated by the cumulative incidence method. RTOG 0234 results were compared to historical control data (the chemoradiation arm of study RTOG-9501/NCT00002670) by 1-sided Gray's test. Hazard ratios were estimated by Cox model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.86
	Comments
	Method	Gray's test
	Comments	Historical control data (RTOG-9501/NCT00002670): n=202, two-year failure rate of 19.9% (12.2% to 27.5%)
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.16
	Confidence Interval	(2-Sided) 95%; 0.72 to 1.87
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference arm = historical control

7. Secondary Outcome

Title	Correlation of EGFR (Total and Phosphorylated) pMAPK, pAKT, Stat-3, KI-67, COX-2, and Cyclin B1 Expression With Local-regional Control, and Overall and Disease-free Survival
Time Frame	From randomization to two years

Outcome Measure Data

Analysis Population Description

Effective and reliable assessment of nuclear expression of these receptors was not achieved and therefore no data was available for analysis.

Arm/Group Title	RT + Cisplatin + Cetuximab	RT + Docetaxel + Cetuximab
Arm/Group Description	Loading dose of cetuximab followed by radiation therapy with weekly cisplatin and cetuximab.	Loading dose of cetuximab followed by radiation therapy (RT) with weekly docetaxel and cetuximab.
Measure Participants	0	0

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-serious adverse events.
Arm/Group Title	RT+Cisplatin+Cetuximab		RT+Docetaxel+Cetuximab
Arm/Group Description	Loading dose of cetuximab followed by radiation therapy with weekly cisplatin and cetuximab.		Loading dose of cetuximab followed by radiation therapy (RT) with weekly docetaxel and cetuximab.
All Cause Mortality
	RT+Cisplatin+Cetuximab		RT+Docetaxel+Cetuximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	RT+Cisplatin+Cetuximab		RT+Docetaxel+Cetuximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/97 (43.3%)		56/106 (52.8%)
Blood and lymphatic system disorders
Febrile neutropenia	4/97 (4.1%)		0/106 (0%)
Hemoglobin	6/97 (6.2%)		2/106 (1.9%)
Cardiac disorders
Atrial fibrillation	0/97 (0%)		2/106 (1.9%)
Cardiac general - Other	0/97 (0%)		2/106 (1.9%)
Cardio-respiratory arrest	1/97 (1%)		0/106 (0%)
Myocardial ischemia	0/97 (0%)		2/106 (1.9%)
Supraventricular arrhythmia NOS	0/97 (0%)		1/106 (0.9%)
Ear and labyrinth disorders
Hearing impaired	2/97 (2.1%)		0/106 (0%)
Tinnitus	1/97 (1%)		0/106 (0%)
Endocrine disorders
Hypothyroidism	2/97 (2.1%)		1/106 (0.9%)
Eye disorders
Conjunctivitis	0/97 (0%)		1/106 (0.9%)
Gastrointestinal disorders
Abdominal pain NOS	1/97 (1%)		1/106 (0.9%)
Acquired tracheo-esophageal fistula	0/97 (0%)		1/106 (0.9%)
Constipation	1/97 (1%)		2/106 (1.9%)
Diarrhea NOS	3/97 (3.1%)		4/106 (3.8%)
Dry mouth	9/97 (9.3%)		13/106 (12.3%)
Dyspepsia	1/97 (1%)		0/106 (0%)
Dysphagia	10/97 (10.3%)		11/106 (10.4%)
Esophageal stenosis acquired	0/97 (0%)		1/106 (0.9%)
Esophagitis NOS	1/97 (1%)		2/106 (1.9%)
Fistula, GI: Oral cavity	0/97 (0%)		2/106 (1.9%)
Gastrointestinal - Other	0/97 (0%)		2/106 (1.9%)
Mucositis/stomatitis (clinical exam): Large bowel	1/97 (1%)		0/106 (0%)
Nausea	7/97 (7.2%)		7/106 (6.6%)
Oral pain	2/97 (2.1%)		5/106 (4.7%)
Radiation mucositis	10/97 (10.3%)		12/106 (11.3%)
Salivary gland disorder NOS	1/97 (1%)		0/106 (0%)
Stomatitis	4/97 (4.1%)		8/106 (7.5%)
Vomiting NOS	5/97 (5.2%)		8/106 (7.5%)
General disorders
Constitutional Symptoms - Other	0/97 (0%)		1/106 (0.9%)
Edema: head and neck	1/97 (1%)		4/106 (3.8%)
Fatigue	5/97 (5.2%)		4/106 (3.8%)
Pain - Other	1/97 (1%)		4/106 (3.8%)
Pyrexia	2/97 (2.1%)		10/106 (9.4%)
Rigors	0/97 (0%)		4/106 (3.8%)
Immune system disorders
Hypersensitivity NOS	2/97 (2.1%)		4/106 (3.8%)
Infections and infestations
Bladder infection NOS	1/97 (1%)		0/106 (0%)
Implant site infection	1/97 (1%)		0/106 (0%)
Infection - Other	1/97 (1%)		3/106 (2.8%)
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Bladder (urinary)	1/97 (1%)		0/106 (0%)
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Middle ear (otitis media)	1/97 (1%)		0/106 (0%)
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Sinus	0/97 (0%)		1/106 (0.9%)
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Skin (cellulitis)	0/97 (0%)		1/106 (0.9%)
Infection with normal ANC or Grade 1 or 2 neutrophils: Blood	0/97 (0%)		1/106 (0.9%)
Infection with normal ANC or Grade 1 or 2 neutrophils: Catheter-related	0/97 (0%)		1/106 (0.9%)
Infection with normal ANC or Grade 1 or 2 neutrophils: Neck NOS	0/97 (0%)		1/106 (0.9%)
Infection with normal ANC or Grade 1 or 2 neutrophils: Salivary gland	1/97 (1%)		0/106 (0%)
Infection with normal ANC or Grade 1 or 2 neutrophils: Wound	1/97 (1%)		0/106 (0%)
Infection with unknown ANC: Neck NOS	0/97 (0%)		1/106 (0.9%)
Infection with unknown ANC: Pharynx	1/97 (1%)		0/106 (0%)
Infection with unknown ANC: Trachea	1/97 (1%)		0/106 (0%)
Infectous meningitis	0/97 (0%)		1/106 (0.9%)
Opportunisitic infection	0/97 (0%)		1/106 (0.9%)
Pneumonia NOS	1/97 (1%)		2/106 (1.9%)
Skin infection	1/97 (1%)		1/106 (0.9%)
Injury, poisoning and procedural complications
Dermatitis radiation NOS	2/97 (2.1%)		6/106 (5.7%)
Radiation recall syndrome	3/97 (3.1%)		4/106 (3.8%)
Investigations
Activated partial thromboplastin time prolonged	0/97 (0%)		1/106 (0.9%)
Alanine aminotransferase increased	2/97 (2.1%)		1/106 (0.9%)
Aspartate aminotransferase increased	1/97 (1%)		2/106 (1.9%)
Blood alkaline phosphatase increased	1/97 (1%)		0/106 (0%)
Blood bilirubin increased	0/97 (0%)		1/106 (0.9%)
Blood creatine phosphokinase increased	0/97 (0%)		1/106 (0.9%)
Blood creatinine increased	2/97 (2.1%)		2/106 (1.9%)
Leukopenia NOS	5/97 (5.2%)		0/106 (0%)
Lymphopenia	5/97 (5.2%)		2/106 (1.9%)
Neutrophil count	5/97 (5.2%)		0/106 (0%)
Platelet count decreased	3/97 (3.1%)		0/106 (0%)
Weight decreased	4/97 (4.1%)		4/106 (3.8%)
Metabolism and nutrition disorders
Anorexia	3/97 (3.1%)		3/106 (2.8%)
Dehydration	8/97 (8.2%)		6/106 (5.7%)
Hyperglycemia NOS	2/97 (2.1%)		3/106 (2.8%)
Hyperkalemia	2/97 (2.1%)		0/106 (0%)
Hypermagnesemia	0/97 (0%)		1/106 (0.9%)
Hypoalbuminemia	2/97 (2.1%)		3/106 (2.8%)
Hypocalcemia	2/97 (2.1%)		1/106 (0.9%)
Hypoglycemia NOS	1/97 (1%)		1/106 (0.9%)
Hypokalemia	1/97 (1%)		2/106 (1.9%)
Hypomagnesemia	3/97 (3.1%)		1/106 (0.9%)
Hyponatremia	1/97 (1%)		1/106 (0.9%)
Musculoskeletal and connective tissue disorders
Back pain	0/97 (0%)		1/106 (0.9%)
Bone pain	1/97 (1%)		0/106 (0%)
Fibrosis-deep connective tissue	1/97 (1%)		2/106 (1.9%)
Musculoskeletal/soft tissue - Other	1/97 (1%)		1/106 (0.9%)
Myositis	0/97 (0%)		1/106 (0.9%)
Neck pain	1/97 (1%)		3/106 (2.8%)
Osteonecrosis	0/97 (0%)		1/106 (0.9%)
Trismus	0/97 (0%)		3/106 (2.8%)
Nervous system disorders
Ataxia	0/97 (0%)		1/106 (0.9%)
Cognitive disorder	0/97 (0%)		1/106 (0.9%)
Depressed level of consciousness	1/97 (1%)		2/106 (1.9%)
Dysgeusia	3/97 (3.1%)		1/106 (0.9%)
Extrapyramidal disorder	0/97 (0%)		1/106 (0.9%)
Headache	1/97 (1%)		2/106 (1.9%)
Mental status changes	0/97 (0%)		1/106 (0.9%)
Neurology - Other	0/97 (0%)		1/106 (0.9%)
Peripheral motor neuropathy	1/97 (1%)		0/106 (0%)
Tremor	0/97 (0%)		1/106 (0.9%)
Psychiatric disorders
Agitation	0/97 (0%)		1/106 (0.9%)
Confusional state	0/97 (0%)		2/106 (1.9%)
Depression	1/97 (1%)		0/106 (0%)
Insomnia	1/97 (1%)		1/106 (0.9%)
Renal and urinary disorders
Renal failure NOS	1/97 (1%)		2/106 (1.9%)
Renal/genitourinary - Other	1/97 (1%)		0/106 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	0/97 (0%)		1/106 (0.9%)
Aspiration	0/97 (0%)		3/106 (2.8%)
Cough	1/97 (1%)		1/106 (0.9%)
Dyspnea	3/97 (3.1%)		2/106 (1.9%)
Epistaxis	1/97 (1%)		0/106 (0%)
Hypoxia	1/97 (1%)		3/106 (2.8%)
Laryngeal edema	1/97 (1%)		0/106 (0%)
Laryngitis NOS	0/97 (0%)		3/106 (2.8%)
Mucositis/stomatitis (clinical exam): Pharynx	3/97 (3.1%)		0/106 (0%)
Mucositis/stomatitis (functional/symptomatic): Pharynx	0/97 (0%)		1/106 (0.9%)
Pharyngeal stenosis	0/97 (0%)		1/106 (0.9%)
Pharyngolaryngeal pain	3/97 (3.1%)		0/106 (0%)
Pneumonitis NOS	2/97 (2.1%)		1/106 (0.9%)
Pulmonary/upper respiratory - Other	0/97 (0%)		1/106 (0.9%)
Skin and subcutaneous tissue disorders
Acne NOS	2/97 (2.1%)		7/106 (6.6%)
Alopecia	1/97 (1%)		1/106 (0.9%)
Dermatitis exfoliative NOS	4/97 (4.1%)		2/106 (1.9%)
Dermatology/skin - Other	4/97 (4.1%)		2/106 (1.9%)
Dry skin	1/97 (1%)		0/106 (0%)
Fat atrophy NOS	0/97 (0%)		1/106 (0.9%)
Nail disorder NOS	1/97 (1%)		0/106 (0%)
Pain of skin	0/97 (0%)		1/106 (0.9%)
Pain: Scalp	0/97 (0%)		1/106 (0.9%)
Photosensitivity reaction NOS	1/97 (1%)		1/106 (0.9%)
Skin fibrosis	3/97 (3.1%)		3/106 (2.8%)
Skin hyperpigmentation	0/97 (0%)		2/106 (1.9%)
Skin hypopigmentation	1/97 (1%)		0/106 (0%)
Telangiectasia	1/97 (1%)		1/106 (0.9%)
Ulceration	0/97 (0%)		1/106 (0.9%)
Urticaria NOS	1/97 (1%)		0/106 (0%)
Vascular disorders
Hypotension NOS	2/97 (2.1%)		2/106 (1.9%)
Other (Not Including Serious) Adverse Events
	RT+Cisplatin+Cetuximab		RT+Docetaxel+Cetuximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	97/97 (100%)		105/106 (99.1%)
Blood and lymphatic system disorders
Blood/bone marrow - Other	6/97 (6.2%)		5/106 (4.7%)
Hemoglobin	57/97 (58.8%)		55/106 (51.9%)
Ear and labyrinth disorders
Auditory/ear - Other	6/97 (6.2%)		5/106 (4.7%)
Hearing impaired	3/97 (3.1%)		10/106 (9.4%)
Tinnitus	5/97 (5.2%)		6/106 (5.7%)
Endocrine disorders
Hypothyroidism	10/97 (10.3%)		15/106 (14.2%)
Gastrointestinal disorders
Abdominal pain NOS	6/97 (6.2%)		7/106 (6.6%)
Constipation	26/97 (26.8%)		35/106 (33%)
Diarrhea NOS	23/97 (23.7%)		23/106 (21.7%)
Dry mouth	79/97 (81.4%)		85/106 (80.2%)
Dyspepsia	7/97 (7.2%)		13/106 (12.3%)
Dysphagia	74/97 (76.3%)		86/106 (81.1%)
Esophageal stenosis acquired	7/97 (7.2%)		8/106 (7.5%)
Esophagitis NOS	9/97 (9.3%)		17/106 (16%)
Gastrointestinal - Other	10/97 (10.3%)		12/106 (11.3%)
Nausea	53/97 (54.6%)		49/106 (46.2%)
Oral pain	29/97 (29.9%)		42/106 (39.6%)
Radiation mucositis	55/97 (56.7%)		65/106 (61.3%)
Salivary gland disorder NOS	29/97 (29.9%)		36/106 (34%)
Stomatitis	21/97 (21.6%)		34/106 (32.1%)
Tooth disorder NOS	6/97 (6.2%)		6/106 (5.7%)
Vomiting NOS	33/97 (34%)		27/106 (25.5%)
General disorders
Edema: head and neck	24/97 (24.7%)		27/106 (25.5%)
Facial pain	3/97 (3.1%)		7/106 (6.6%)
Fatigue	76/97 (78.4%)		83/106 (78.3%)
Pain - Other	12/97 (12.4%)		9/106 (8.5%)
Pyrexia	16/97 (16.5%)		16/106 (15.1%)
Rigors	7/97 (7.2%)		11/106 (10.4%)
Infections and infestations
Gingival infection	6/97 (6.2%)		3/106 (2.8%)
Infection - Other	10/97 (10.3%)		8/106 (7.5%)
Injury, poisoning and procedural complications
Dermatitis radiation NOS	39/97 (40.2%)		47/106 (44.3%)
Radiation recall syndrome	29/97 (29.9%)		19/106 (17.9%)
Investigations
Alanine aminotransferase increased	8/97 (8.2%)		16/106 (15.1%)
Aspartate aminotransferase increased	17/97 (17.5%)		24/106 (22.6%)
Blood alkaline phosphatase increased	7/97 (7.2%)		16/106 (15.1%)
Blood bilirubin increased	7/97 (7.2%)		8/106 (7.5%)
Blood creatinine increased	5/97 (5.2%)		5/106 (4.7%)
Leukopenia NOS	51/97 (52.6%)		29/106 (27.4%)
Lymphopenia	20/97 (20.6%)		24/106 (22.6%)
Metabolic/laboratory - Other	7/97 (7.2%)		11/106 (10.4%)
Neutrophil count	20/97 (20.6%)		6/106 (5.7%)
Platelet count decreased	17/97 (17.5%)		10/106 (9.4%)
Weight decreased	51/97 (52.6%)		43/106 (40.6%)
Metabolism and nutrition disorders
Anorexia	51/97 (52.6%)		41/106 (38.7%)
Dehydration	28/97 (28.9%)		12/106 (11.3%)
Hypercalcemia	9/97 (9.3%)		4/106 (3.8%)
Hyperglycemia NOS	40/97 (41.2%)		30/106 (28.3%)
Hyperkalemia	13/97 (13.4%)		9/106 (8.5%)
Hypermagnesemia	4/97 (4.1%)		7/106 (6.6%)
Hypoalbuminemia	22/97 (22.7%)		29/106 (27.4%)
Hypocalcemia	16/97 (16.5%)		20/106 (18.9%)
Hypokalemia	19/97 (19.6%)		17/106 (16%)
Hypomagnesemia	24/97 (24.7%)		10/106 (9.4%)
Hyponatremia	38/97 (39.2%)		30/106 (28.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	6/97 (6.2%)		5/106 (4.7%)
Fibrosis-cosmesis	7/97 (7.2%)		11/106 (10.4%)
Fibrosis-deep connective tissue	11/97 (11.3%)		20/106 (18.9%)
Muscle weakness NOS	6/97 (6.2%)		4/106 (3.8%)
Musculoskeletal/soft tissue - Other	5/97 (5.2%)		11/106 (10.4%)
Myalgia	5/97 (5.2%)		3/106 (2.8%)
Neck pain	20/97 (20.6%)		16/106 (15.1%)
Trismus	17/97 (17.5%)		24/106 (22.6%)
Nervous system disorders
Dizziness	16/97 (16.5%)		5/106 (4.7%)
Dysgeusia	53/97 (54.6%)		52/106 (49.1%)
Headache	31/97 (32%)		28/106 (26.4%)
Peripheral sensory neuropathy	12/97 (12.4%)		12/106 (11.3%)
Psychiatric disorders
Anxiety	9/97 (9.3%)		8/106 (7.5%)
Depression	14/97 (14.4%)		13/106 (12.3%)
Insomnia	12/97 (12.4%)		19/106 (17.9%)
Respiratory, thoracic and mediastinal disorders
Aspiration	5/97 (5.2%)		8/106 (7.5%)
Cough	19/97 (19.6%)		25/106 (23.6%)
Dyspnea	11/97 (11.3%)		14/106 (13.2%)
Laryngeal edema	5/97 (5.2%)		9/106 (8.5%)
Laryngitis NOS	25/97 (25.8%)		28/106 (26.4%)
Mucositis/stomatitis (clinical exam): Pharynx	13/97 (13.4%)		4/106 (3.8%)
Mucositis/stomatitis (functional/symptomatic): Pharynx	7/97 (7.2%)		9/106 (8.5%)
Pharyngolaryngeal pain	21/97 (21.6%)		18/106 (17%)
Skin and subcutaneous tissue disorders
Acne NOS	60/97 (61.9%)		57/106 (53.8%)
Alopecia	17/97 (17.5%)		22/106 (20.8%)
Dermatitis exfoliative NOS	23/97 (23.7%)		33/106 (31.1%)
Dermatology/skin - Other	12/97 (12.4%)		16/106 (15.1%)
Dry skin	12/97 (12.4%)		15/106 (14.2%)
Erythema multiforme	3/97 (3.1%)		8/106 (7.5%)
Pruritus	9/97 (9.3%)		13/106 (12.3%)
Skin fibrosis	30/97 (30.9%)		37/106 (34.9%)
Skin hyperpigmentation	23/97 (23.7%)		20/106 (18.9%)
Sweating increased	1/97 (1%)		6/106 (5.7%)
Telangiectasia	6/97 (6.2%)		15/106 (14.2%)
Vascular disorders
Hypotension NOS	9/97 (9.3%)		4/106 (3.8%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.