Radiation Therapy With Cisplatin or Cetuximab in Treating Patients With Oropharyngeal Cancer

Head and Neck Cancer Clinical Trial

Official title:

Phase III Trial of Radiotherapy Plus Cetuximab Versus Chemoradiotherapy in HPV-Associated Oropharynx Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01302834
• Other study ID #: RTOG-1016
• Secondary ID: CDR0000695731NCI
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 2011

Study information

• Verified date: August 2022
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether radiation therapy is more effective with cisplatin or cetuximab in treating oropharyngeal cancer.

PURPOSE: This phase III trial is studying radiation therapy with cisplatin or cetuximab to see how well it works in treating patients with oropharyngeal cancer.

Description:

OBJECTIVES:

Primary

• To determine whether substitution of cisplatin with cetuximab will result in comparable 5-year overall survival.

Secondary

• To monitor and compare progression-free survival for "safety".

• To compare patterns of failure (locoregional vs distant).

• To compare acute toxicity profiles (and overall toxicity burden).

• To compare overall quality of life (QOL) short-term (< 6 months) and long-term (1 year).

• To compare QOL Swallowing Domains short-term and long-term.

• To compare clinician-reported versus patient-reported CTCAE toxicity events.

• To explore differences in the cost effectiveness of cetuximab as compared to cisplatin.

• To explore differences in work status and time to return to work.

• To compare patient-reported changes in hearing.

• To compare CTCAE v. 4 late toxicity at 1, 2, and 5 years.

• To evaluate the effect of tobacco exposure (and other exposures) as measured by standardized computer-assisted self interview (CASI) on overall survival and progression-free survival.

• To pilot CASI collection of patient reported outcomes in a cooperative group setting.

• To determine whether specific molecular profiles are associated with overall or progression-free survival.

• To investigate associations between changes in serum biomarkers or human papilloma virus (HPV)-specific cellular immune responses measured at baseline and three months with overall or progression-free survival.

OUTLINE: This is a multicenter study. Patients are stratified according to T stage (T1-2 vs T 3-4), N stage (N0-2a vs N2b-3), Zubrod performance status (0 vs 1), and smoking history (≤ 10 pack-years vs > 10 pack-years). Patients are randomized to 1 of 2 treatment arms.

Patients may complete quality-of-life questionnaires and risk factors for head and neck cancer surveys at baseline, periodically during study, and at follow-up for 1 year.

After completion of study therapy, patients are followed up at 1-3 months, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 987
• Est. primary completion date: July 12, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

Inclusion Criteria:

1. Pathologically (histologically or cytologically) proven diagnosis of squamous cell carcinoma (including the histological variants papillary squamous cell carcinoma and basaloid squamous cell carcinoma) of the oropharynx (tonsil, base of tongue, soft palate, or oropharyngeal walls).

2. Patients must be positive for p16, determined by central review prior to randomization.

3. Patients must have clinically or radiographically evident measurable disease at the primary site or at nodal stations. Tonsillectomy or local excision of the primary without removal of nodal disease is permitted, as is excision removing gross nodal disease but with intact primary site. Limited neck dissections retrieving = 4 nodes are permitted and considered as non-therapeutic nodal excisions. Fine needle aspirations of the neck are insufficient due to limited tissue for retrospective central review. Biopsy specimens from the primary or nodes measuring at least 3-5 mm are required.

4. Clinical stage T1-2, N2a-N3 or T3-4, any N (AJCC, 7th ed.; see Appendix III), including no distant metastases, based upon the following minimum diagnostic workup:

• General history and physical examination by a radiation oncologist and medical oncologist within 8 weeks prior to registration;

• Examination by an ear, nose, and throat (ENT) or head and neck surgeon, including laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure) within 8 weeks prior to registration;

• One of the following combinations of imaging is required within 8 weeks prior to registration:

1. A computerized tomography (CT) scan of the neck (with contrast) and a chest CT scan (with or without contrast);

2. or a magnetic resonance imaging (MRI) scan of the neck (with contrast) and a chest CT scan (with or without contrast);

3. or a CT scan of neck (with contrast) and a positron emission tomography (PET)/CT of neck and chest (with or without contrast);

4. or an MRI of the neck (with contrast) and a PET/CT of neck and chest (with or without contrast).

Note: A CT scan of neck and/or a PET/CT performed for radiation planning and read by a radiologist may serve as both staging and planning tools.

5. Zubrod Performance Status 0-1 within 2 weeks prior to registration

6. Age = 18;

7. Complete blood count (CBC)/differential obtained within 2 weeks prior to registration on study, with adequate bone marrow function, defined as follows:

• Absolute neutrophil count (ANC) > 1,500 cells/mm3;

• Platelets > 100,000 cells/mm3;

• Hemoglobin (Hgb) > 8.0 g/dl; Note: The use of transfusion or other intervention to achieve Hgb > 8.0 g/dl is acceptable.

8. Adequate hepatic function, defined as follows:

• Bilirubin < 2 mg/dl within 2 weeks prior to registration;

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 x the upper limit of normal within 2 weeks prior to registration;

9. Adequate renal function, defined as follows:

• Serum creatinine < 1.5 mg/dl within 2 weeks prior to registration or creatinine clearance (CCr) = 50 ml/min within 2 weeks prior to registration determined by 24-hour collection or estimated by Cockcroft-Gault formula:

CCr male = [(140 - age) x (wt in kg)] [(Serum Cr mg/dl) x (72)] CCr female = 0.85 x (CCr male)

10. Patients must provide their smoking history (for stratification) via the computer-assisted self interview (CASI) head and neck risk factor survey tool.

11. Negative serum pregnancy test within 2 weeks prior to registration for women of childbearing potential;

12. Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study and until at least 60 days following the last study treatment.

13. Patients who are human immunodeficiency virus (HIV) positive but have no prior acquired immune deficiency syndrome (AIDS) -defining illness and have CD4 cells of at least 350/mm3 are eligible. Patient HIV status must be known prior to registration. Patients must not be sero-positive for Hepatitis B (Hepatitis B surface antigen positive or anti-hepatitis B core antigen positive) or sero-positive for Hepatitis C (anti-Hepatitis C antibody positive). However, patients who are immune to hepatitis B (anti-Hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B). HIV-positive patients must not have multi-drug resistant HIV infection or other concurrent AIDS-defining conditions.

14. Patient must provide study specific informed consent prior to study entry, including consent for mandatory submission of tissue for required, central p16 review and consent to participate in the computer-assisted self interview (CASI) survey questions regarding smoking history.

Exclusion Criteria:

1. Cancers considered to be from an oral cavity site (oral tongue, floor mouth, alveolar ridge, buccal or lip), nasopharynx, hypopharynx, or larynx, even if p16 positive, are excluded. Carcinoma of the neck of unknown primary site origin (even if p16 positive) are excluded from participation.

2. Stage T1-2, N0-1;

3. Distant metastasis or adenopathy below the clavicles;

4. Gross total excision of both primary and nodal disease; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease.

5. Simultaneous primaries or bilateral tumors;

6. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (For example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible);

7. Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable;

8. Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields;

9. Severe, active co-morbidity, defined as follows:

• 9.1 Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months;

• 9.2 Transmural myocardial infarction within the last 6 months;

• 9.3 Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;

• 9.4 Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration;

• 9.5 Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol.

• 9.6 Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition with immune compromise greater than that noted in Section 3.1.13; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immuno-compromised patients.

10. Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.

11. Prior allergic reaction to cisplatin or cetuximab;

12. Prior cetuximab or other anti-EGFR therapy.

Related Conditions & MeSH terms

• Head and Neck Cancer
• Precancerous Condition
• Precancerous Conditions

Intervention

Biological:
• cetuximab
400 mg/m2 IV 5-7 days before IMRT then 250 mg/m2 IV weekly for 7 weeks

Drug:
• cisplatin
100 mg/m2 IV on days 1 and 22 of IMRT

Radiation:
• IMRT
35 fractions over 6 weeks, 6 fractions per week, 2 Gray per fraction to total dose of 70 Gy.

Locations

Country	Name	City	State
Canada	McGill Cancer Centre at McGill University	Montreal	Quebec
Canada	CancerCare Manitoba	Winnipeg	Manitoba
United States	Rosenfeld Cancer Center at Abington Memorial Hospital	Abington	Pennsylvania
United States	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	McFarland Clinic, PC	Ames	Iowa
United States	Providence Cancer Center	Anchorage	Alaska
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	Theda Care Cancer Institute	Appleton	Wisconsin
United States	Northwest Community Hospital	Arlington Heights	Illinois
United States	Mission Hospitals - Memorial Campus	Asheville	North Carolina
United States	Georgia Cancer Center for Excellence at Grady Memorial Hospital	Atlanta	Georgia
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Auburn Radiation Oncology	Auburn	California
United States	Rocky Mountain Cancer Centers - Aurora	Aurora	Colorado
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland
United States	St. Agnes Hospital Cancer Center	Baltimore	Maryland
United States	Barberton Citizens Hospital	Barberton	Ohio
United States	Mary Bird Perkins Cancer Center - Baton Rouge	Baton Rouge	Louisiana
United States	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan
United States	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana
United States	St. Joseph Cancer Center	Bellingham	Washington
United States	Billings Clinic - Downtown	Billings	Montana
United States	Lourdes Regional Cancer Center	Binghamton	New York
United States	Boulder Community Hospital	Boulder	Colorado
United States	Roy and Patricia Disney Family Cancer Center at Providence Saint Joseph Medical Center	Burbank	California
United States	Lahey Clinic Medical Center - Burlington	Burlington	Massachusetts
United States	Radiation Oncology Centers - Cameron Park	Cameron Park	California
United States	Cancer Institute of Cape Girardeau, LLC	Cape Girardeau	Missouri
United States	Mercy Cancer Center at Mercy San Juan Medical Center	Carmichael	California
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina
United States	Creticos Cancer Center at Advocate Illinois Masonic Medical Center	Chicago	Illinois
United States	John H. Stroger, Jr. Hospital of Cook County	Chicago	Illinois
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Enloe Cancer Center at Enloe Medical Center	Chico	California
United States	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Case Comprehensive Cancer Center	Cleveland	Ohio
United States	Cleveland Clinic Cancer Center at Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado
United States	Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Payson Center for Cancer Care at Concord Hospital	Concord	New Hampshire
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	NSMC Cancer Center - Peabody	Danvers	Massachusetts
United States	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois
United States	North Broward Medical Center	Deerfield Beach	Florida
United States	Porter Adventist Hospital	Denver	Colorado
United States	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa
United States	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan
United States	Seacoast Cancer Center at Wentworth - Douglass Hospital	Dover	New Hampshire
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Dale and Frances Hughes Cancer Center at Pocono Medical Center	East Stroudsburg	Pennsylvania
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Swedish Medical Center	Englewood	Colorado
United States	Evanston Hospital	Evanston	Illinois
United States	Hudner Oncology Center at Saint Anne's Hospital - Fall River	Fall River	Massachusetts
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Parkview Regional Cancer Center at Parkview Health	Fort Wayne	Indiana
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	University of Texas Medical Branch	Galveston	Texas
United States	Adams Cancer Center	Gettysburg	Pennsylvania
United States	Center for Cancer Care at Goshen General Hospital	Goshen	Indiana
United States	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan
United States	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan
United States	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Moses Cone Regional Cancer Center at Wesley Long Community Hospital	Greensboro	North Carolina
United States	Cancer Centers of the Carolinas - Faris Road	Greenville	South Carolina
United States	CCOP - Greenville	Greenville	South Carolina
United States	Cherry Tree Cancer Center	Hanover	Pennsylvania
United States	M. D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	Edwards Comprehensive Cancer Center at Cabell Huntington Hospital	Huntington	West Virginia
United States	Community Regional Cancer Care at Community Hospital East	Indianapolis	Indiana
United States	Community Regional Cancer Care at Community Hospital North	Indianapolis	Indiana
United States	Baptist Cancer Institute - Jacksonville	Jacksonville	Florida
United States	Baptist Medical Center South	Jacksonville	Florida
United States	Integrated Community Oncology Network at Southside Cancer Center	Jacksonville	Florida
United States	Integrated Community Oncology Network	Jacksonville Beach	Florida
United States	Kansas City Cancer Centers - North	Kansas City	Missouri
United States	Kansas City Cancer Centers - South	Kansas City	Missouri
United States	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas
United States	Kingsbury Center for Cancer Care at Cheshire Medical Center	Keene	New Hampshire
United States	Kinston Medical Specialists	Kinston	North Carolina
United States	Gundersen Lutheran Center for Cancer and Blood	La Crosse	Wisconsin
United States	Rebecca and John Moores UCSD Cancer Center	La Jolla	California
United States	St. Mary Regional Cancer Center	Langhorne	Pennsylvania
United States	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Lucille P. Markey Cancer Center at University of Kentucky	Lexington	Kentucky
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky
United States	McKee Medical Center	Loveland	Colorado
United States	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin
United States	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin
United States	Northwest Ohio Oncology Center	Maumee	Ohio
United States	Hillcrest Cancer Center at Hillcrest Hospital	Mayfield Heights	Ohio
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	Dubs Cancer Center at Rogue Valley Medical Center	Medford	Oregon
United States	Providence Cancer Center at PMCC	Medford	Oregon
United States	Lake/University Ireland Cancer Center	Mentor	Ohio
United States	University of Miami Sylvester Comprehensive Cancer Center - Miami	Miami	Florida
United States	Southwest General Health Center	Middleburg Heights	Ohio
United States	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	Veterans Affairs Medical Center - Milwaukee	Milwaukee	Wisconsin
United States	Michiana Hematology-Oncology, PC - South Bend	Mishawaka	Indiana
United States	Cancer Center at Ball Memorial Hospital	Muncie	Indiana
United States	Jon and Karen Huntsman Cancer Center at Intermountain Medical Center	Murray	Utah
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus	New Britain	Connecticut
United States	CCOP - Ochsner	New Orleans	Louisiana
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Sentara Cancer Institute at Sentara Norfolk General Hospital	Norfolk	Virginia
United States	Kaiser Permanente - Division of Research - Oakland	Oakland	California
United States	Val and Ann Browning Cancer Center at McKay-Dee Hospital Center	Ogden	Utah
United States	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma
United States	Methodist Estabrook Cancer Center	Omaha	Nebraska
United States	Nebraska Medical Center	Omaha	Nebraska
United States	Integrated Community Oncology Network - Orange Park	Orange Park	Florida
United States	St. Charles Mercy Hospital	Oregon	Ohio
United States	Florida Hospital Cancer Institute at Florida Hospital Orlando	Orlando	Florida
United States	M.D. Anderson Cancer Center at Orlando	Orlando	Florida
United States	Kansas City Cancer Centers - Southwest	Overland Park	Kansas
United States	Florida Cancer Center - Palatka	Palatka	Florida
United States	Regional Cancer Center at Singing River Hospital	Pascagoula	Mississippi
United States	Sacred Heart Cancer Center at Sacred Heart Hospital	Pensacola	Florida
United States	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania
United States	FirstHealth Moore Regional Community Hospital Comprehensive Cancer Center	Pinehurst	North Carolina
United States	Knight Cancer Institute at Oregon Health and Science University	Portland	Oregon
United States	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon
United States	Providence St. Vincent Medical Center	Portland	Oregon
United States	CCOP - Kansas City	Prairie Village	Kansas
United States	Utah Valley Regional Medical Center - Provo	Provo	Utah
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center	Reading	Pennsylvania
United States	Renown Institute for Cancer at Renown Regional Medical Center	Reno	Nevada
United States	Highland Hospital of Rochester	Rochester	New York
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	Rohnert Park Cancer Center	Rohnert Park	California
United States	Radiation Oncology Center - Roseville	Roseville	California
United States	Mercy General Hospital	Sacramento	California
United States	Radiological Associates of Sacramento Medical Group, Incorporated	Sacramento	California
United States	Flagler Cancer Center	Saint Augustine	Florida
United States	Barnes-Jewish West County Hospital	Saint Louis	Missouri
United States	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri
United States	David C. Pratt Cancer Center at St. John's Mercy	Saint Louis	Missouri
United States	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri
United States	Park Nicollet Cancer Center	Saint Louis Park	Minnesota
United States	Regions Hospital Cancer Care Center	Saint Paul	Minnesota
United States	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah
United States	Utah Cancer Specialists at UCS Cancer Center	Salt Lake City	Utah
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia
United States	Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler	Savannah	Georgia
United States	Maine Center for Cancer Medicine and Blood Disorders - Scarborough	Scarborough	Maine
United States	CCOP - Virginia Mason Research Center	Seattle	Washington
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Kaiser Permanente Medical Center - South San Francisco	South San Francisco	California
United States	Frederick R. and Betty M. Smith Cancer Treatment Center	Sparta	New Jersey
United States	Cancer Centers of the Carolinas - Spartanburg	Spartanburg	South Carolina
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	Cancer Institute at St. John's Hospital	Springfield	Illinois
United States	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri
United States	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois
United States	Flower Hospital Cancer Center	Sylvania	Ohio
United States	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida	Tampa	Florida
United States	North Suburban Medical Center	Thornton	Colorado
United States	St. Anne Mercy Hospital	Toledo	Ohio
United States	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma
United States	Solano Radiation Oncology Center	Vacaville	California
United States	Northwest Cancer Specialists at Vancouver Cancer Center	Vancouver	Washington
United States	Coastal Cancer Center at Sentara Virginia Beach General Hospital	Virginia Beach	Virginia
United States	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey
United States	University of Wisconcin Cancer Center at Aspirus Wausau Hospital	Wausau	Wisconsin
United States	Precision Radiotherapy at University Pointe	West Chester	Ohio
United States	UHHS Westlake Medical Center	Westlake	Ohio
United States	Schiffler Cancer Center at Wheeling Hospital	Wheeling	West Virginia
United States	Cancer Treatment Center	Wooster	Ohio
United States	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington
United States	York Cancer Center at Apple Hill Medical Center	York	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI), NRG Oncology

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

Gillison ML, Trotti AM, Harris J, Eisbruch A, Harari PM, Adelstein DJ, Jordan RCK, Zhao W, Sturgis EM, Burtness B, Ridge JA, Ringash J, Galvin J, Yao M, Koyfman SA, Blakaj DM, Razaq MA, Colevas AD, Beitler JJ, Jones CU, Dunlap NE, Seaward SA, Spencer S, G — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	An event for overall survival is death due to any cause. Survival time is defined as time from randomization to the date of death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. The protocol endpoint is hazard ratio, which is reported in the statistical analysis results. Five-year rate is reported simply as summary data; it is not the outcome measure.	From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 133 deaths were reported. Maximum follow-up at time of analysis was 6.5 years.
Secondary	Progression-free Survival	An event for progression-free survival is local, regional, or distant disease progression or death due to any cause. Progression-free survival time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. The protocol endpoint is the distribution of progression-free survival times, for which the hazard ratio is reported in the statistical analysis results. Five-year rate is reported simply as summary data; it is not the outcome measure.	From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 133 deaths were reported. Maximum follow-up at time of analysis was 6.5 years.
Secondary	Time to Local-regional Failure	Failure for local-regional failure endpoint was defined as local or regional progression, salvage surgery of the primary tumor with tumor present/unknown, salvage neck dissection with tumor present/unknown > 20 weeks after the end of radiation therapy, death due to study cancer without documented progression, or death due to unknown causes without documented progression; distant metastasis and death due to other causes were considered competing risks. Local-regional failure time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Rates are estimated by the cumulative incidence method. The protocol endpoint is the distribution of local-regional failure times, for which the hazard ratio is reported in the statistical analysis results. Five-year rate is reported simply as summary data; it is not the outcome measure.	From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 133 deaths were reported. Maximum follow-up at time of analysis was 6.5 years.
Secondary	Time to Distant Metastasis	Failure for distant metastasis endpoint was defined as distant progression; local-regional failure and death due to any cause were considered competing risks. Distant metastasis time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Rates are estimated by the cumulative incidence method. The protocol endpoint is the distribution of distant metastasis times, for which the hazard ratio is reported in the statistical analysis results. Five-year rate is reported simply as summary data; it is not the outcome measure.	From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 133 deaths were reported. Maximum follow-up at time of analysis was 6.5 years.
Secondary	Time to Secondary Primary Cancer	Failure for second primary endpoint was defined as reporting of a new primary cancer; death due to any cause was considered a competing risk. Second primary time is defined as time from randomization to the date of second primary or last known follow-up (censored). Rates are estimated by the cumulative incidence method. The protocol endpoint is the distribution of second primary cancer times, for which the hazard ratio is reported in the statistical analysis results. Five-year rate is reported simply as summary data; it is not the outcome measure.	From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 133 deaths were reported. Maximum follow-up at time of analysis was 6.5 years.
Secondary	Distribution of First Progression Events	The first event type for progression-free survival is counted for each participant. Possible first progression events are local, regional, or distant progression, any combination of these, or death. The frequency table of these events is also referred to as "Pattern of failure."	From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 133 deaths were reported. Maximum follow-up at time of analysis was 6.5 years.
Secondary	Percentage of Participants Experiencing Early Death	Early death is defined as death due to adverse event or within 30 days of treatment completion.	From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 133 deaths were reported. Maximum follow-up at time of analysis was 6.5 years.
Secondary	Percentage of Participants With Acute Grade 3-4 Treatment-related Adverse Events: During Treatment	Acute adverse events (AE) are defined as occurring within 180 days from the end of treatment. "Treatment-related" means reported as definitely, probably, or possibly related to protocol treatment. AE were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE	From start of treatment to end of treatment, approximately 6 weeks
Secondary	Percentage of Participants With Acute Grade 3-4 Treatment-related Adverse Events: 1 Month After End of Study Treatment	Acute adverse events (AE) are defined as occurring within 180 days from the end of treatment. "Treatment-related" means reported as definitely, probably, or possibly related to protocol treatment. AE were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE	From start of treatment to approximately 2.5 months (1 month after the end of treatment)
Secondary	Percentage of Participants With Acute Grade 3-4 Treatment-related Adverse Events: 3 Months After the End of Study Treatment	Acute adverse events (AE) are defined as occurring within 180 days from the end of treatment. "Treatment-related" means reported as definitely, probably, or possibly related to protocol treatment. AE were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE	From start of treatment to approximately 4.5 months (3 months after the end of treatment)
Secondary	Percentage of Participants With Acute Grade 3-4 Treatment-related Adverse Events: 6 Months After the End of Study Treatment	Acute adverse events (AE) are defined as occurring within 180 days from the end of treatment. "Treatment-related" means reported as definitely, probably, or possibly related to protocol treatment. AE were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE	From start of treatment to approximately 7.5 months (6 months after the end of treatment)
Secondary	Percentage of Participants With Late Grade 3-4 Treatment-related Adverse Events: 1 Year After the End of Study Treatment	Late adverse events (AE) are defined as > 180 days from end of treatment. "Treatment-related" means reported as definitely, probably, or possibly related to protocol treatment. AE were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE	From start of treatment to approximately 13.5 months (one year after the end of treatment)
Secondary	Percentage of Participants With Late Grade 3-4 Treatment-related Adverse Events: 2 Years After the End of Study Treatment	Late adverse events (AE) are defined as > 180 days from end of treatment. "Treatment-related" means reported as definitely, probably, or possibly related to protocol treatment. AE were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE	From 180 days after end of treatment to two years after end of treatment.
Secondary	Percentage of Participants With Late Grade 3-4 Treatment-related Adverse Events: 5 Years After the End of Study Treatment	Late adverse events (AE) are defined as > 180 days from end of treatment. "Treatment-related" means reported as definitely, probably, or possibly related to protocol treatment. AE were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE	From start of treatment to approximately 61.5 months (five years after the end of treatment)
Secondary	Percentage of Participants With a Feeding Tube at 1 Year		From randomization to 1 year.
Secondary	EORTC QLQ-C30 at Baseline, End of Treatment, 3, 6, and 12 Months From End of Treatment.		From randomization to 1 year after end of treatment.
Secondary	EORTC QLQ-H&N35 at Baseline, End of Treatment, 3, 6, and 12 Months From End of Treatment.		From randomization to 1 year after end of treatment.
Secondary	Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events for Head and Neck (PRO-CTCAE H&N) at Baseline, End of Treatment, 3, 6, and 12 Months From End of Treatment.		From randomization to 1 year after end of treatment.
Secondary	EuroQol Five Dimension Scale (EQ-5D) at Baseline, End of Treatment, 3, 6, and 12 Months From End of Treatment.		From randomization to 1 year after end of treatment.
Secondary	Work Status Questionnaire at Baseline, End of Treatment, 3, 6, and 12 Months.		From randomization to 1 year after end of treatment.
Secondary	Percentage of Patients With Normal/Good Dental Health: Pretreatment	This study utilized a dental effects health scale from 0 (normal) to 4 (life-threatening dental condition). The percentage of participants with a value of 0 or 1 is reported: 0 = "Normal: Edentulous, with no gingival disease"; 1 = "Mild changes/good dental health: mild periodontal inflammation-routine cleaning indicated; < 5 restorations indicated; no extractions indicated." Ten year data is not yet available.	Before treatment
Secondary	Percentage of Patients With Normal/Good Dental Health: 1 Year After End of Treatment	This study utilized a dental effects health scale from 0 (normal) to 4 (life-threatening dental condition). The percentage of participants with a value of 0 or 1 is reported: 0 = "Normal: Edentulous, with no gingival disease"; 1 = "Mild changes/good dental health: mild periodontal inflammation-routine cleaning indicated; < 5 restorations indicated; no extractions indicated."	1 year after end of treatment (approximately 13.5 months)
Secondary	Percentage of Patients With Normal/Good Dental Health: 2 Years After End of Treatment	This study utilized a dental effects health scale from 0 (normal) to 4 (life-threatening dental condition). The percentage of participants with a value of 0 or 1 is reported: 0 = "Normal: Edentulous, with no gingival disease"; 1 = "Mild changes/good dental health: mild periodontal inflammation-routine cleaning indicated; < 5 restorations indicated; no extractions indicated."	2 years after end of treatment (approximately 25.5 months)
Secondary	Percentage of Patients With Normal/Good Dental Health: 5 Years After End of Treatment	This study utilized a dental effects health scale from 0 (normal) to 4 (life-threatening dental condition). The percentage of participants with a value of 0 or 1 is reported: 0 = "Normal: Edentulous, with no gingival disease"; 1 = "Mild changes/good dental health: mild periodontal inflammation-routine cleaning indicated; < 5 restorations indicated; no extractions indicated."	5 years after end of treatment (approximately 61.5 months)
Secondary	Percentage of Patients With Normal/Good Dental Health: 10 Years After End of Treatment	his study utilized a dental effects health scale from 0 (normal) to 4 (life-threatening dental condition). The percentage of participants with a value of 0 or 1 is reported: 0 = "Normal: Edentulous, with no gingival disease"; 1 = "Mild changes/good dental health: mild periodontal inflammation-routine cleaning indicated; < 5 restorations indicated; no extractions indicated."	10 years after end of treatment (approximately 121.5 months)
Secondary	Hearing Quality of Life Outcomes as Measured by the Hearing Handicap Inventory for Adults (HHIA-S) at Baseline, End of Treatment and at 3, 6, and 12 Months From End of Treatment.		From randomization to 1 year after end of treatment.
Secondary	Behavioral Risk Assessment Survey (BRASS) at Baseline.		Prior to randomization.
Secondary	Translational Research Analysis		From randomization to date of death or last follow-up.