Reduced-Dose Intensity-Modulated Radiation Therapy With or Without Cisplatin in Treating Patients With Advanced Oropharyngeal Cancer

Stage IVA Oropharyngeal Squamous Cell Carcinoma Clinical Trial

Official title:

A Randomized Phase II Trial for Patients With p16 Positive, Non-Smoking Associated, Locoregionally Advanced Oropharyngeal Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02254278
• Other study ID #: NRG-HN002
• Secondary ID: NCI-2014-01279NR
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 2014
• Est. completion date: May 31, 2024

Study information

• Verified date: October 2021
• Source: NRG Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase II trial studies the side effects and how well modestly reduced-dose intensity-modulated radiation therapy (IMRT) with or without cisplatin works in treating patients with oropharyngeal cancer that has spread to other places in the body (advanced). Radiation therapy uses high energy x rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether IMRT is more effective with or without cisplatin in treating patients with oropharyngeal cancer.

Description:

PRIMARY OBJECTIVES: -To select the arm(s) achieving a 2-year progression-free survival rate of >= 85% without unacceptable swallowing toxicity at 1 year. SECONDARY OBJECTIVES: - To determine patterns of failure (locoregional relapse versus distant) and survival -(overall and progression-free) at 6 months and 2 years. - To determine acute toxicity profiles at the end of radiation therapy and at 1 and 6 months. - To determine late toxicity profiles at 1 and 2 years. - To determine patient-reported swallowing outcomes at 6 months and 1 and 2 years. - To determine the predictive value of 12-14 week, post-treatment fludeoxyglucose F 18 (FDG)-positron emission tomography (PET)/computed tomography (CT) for locoregional control and progression free survival (PFS) at 2 years. - To determine the predictive value of blood and tissue biomarkers for disease outcomes at 2 years. - To determine swallowing recovery per videofluoroscopy imaging at 2 years. After completion of study treatment, patients are followed at 1 and 3 months then every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 316
• Est. completion date: May 31, 2024
• Est. primary completion date: June 10, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

Step 1: Registration:

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); cytologic diagnosis from a cervical lymph node is sufficient in the presence of clinical evidence of a primary tumor in the oropharynx. Clinical evidence should be documented, may consist of palpation, imaging, or endoscopic evaluation, and should be sufficient to estimate the size of the primary (for T stage).

2. 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.

3. Immunohistochemical staining for p16 must be performed on tissue, and this tissue must be submitted for central review. Fine needle aspiration (FNA) biopsy specimens may be used as the sole diagnostic tissue if formalin-fixed paraffin-embedded cell block material is available for p16 immunohistochemistry. FNA specimens prepared with adequate p16 testing in this manner are acceptable to submit for central review. If the p16 preparation is not adequate, additional specimens will be required to establish p16 status. Centers are encouraged to contact the pathology chairs for clarification.

4. Clinical stage T1-T2, N1-N2b or T3, N0-N2b (AJCC, 7th ed.) including no distant

metastases based on the following diagnostic workup:

• General history and physical examination within 56 days prior to registration;
• Fiberoptic exam with laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure) within 70 days prior to registration;
• One of the following combinations of imaging is required within 56 days prior to

registration:

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

2. or an MRI 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 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 the purposes of radiation planning may serve as both staging and planning tools.

5. Patients must provide their personal smoking history prior to registration. The lifetime cumulative history cannot exceed 10 pack-years. The following formula is used to calculate the pack-years during the periods of smoking in the patient's life; the cumulative total of the number of pack-years during each period of active smoking is the lifetime cumulative history. Number of pack-years = [Frequency of smoking (number of cigarettes per day) × duration of cigarette smoking (years)] / 20 Note: Twenty cigarettes is considered equivalent to one pack. The effect of non-cigarette tobacco products on the survival of patients with p16-positive oropharyngeal cancers is undefined. While there are reportedly increased risks of head and neck cancer associated with sustained heavy cigar and pipe use (Wyss 2013), such sustained use of non-cigarette products is unusual and does not appear to convey added risk with synchronous cigarette smoking. Cigar and pipe tobacco consumption is therefore not included in calculating the lifetime pack-years. Marijuana consumption is likewise not considered in this calculation. There is no clear scientific evidence regarding the role of chewing tobacco-containing products in this disease, although this is possibly more concerning given the proximity of the oral cavity and oropharynx. In any case, investigators are discouraged from enrolling patients with a history of very sustained use (such as several years or more) of non-cigarette tobacco products alone.

6. Zubrod Performance Status of 0-1 within 56 days prior to registration;

7. Age = 18;

8. The trial is open to both genders;

9. Adequate hematologic function within 14 days prior to registration, 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.

10. Adequate renal function within 14 days prior to registration, defined as follows:

• Serum creatinine (Cr) < 1.5 mg/dl or creatinine clearance (CC) = 50 ml/min

determined by 24-hour collection or estimated by Cockcroft-Gault formula:

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

11. Adequate hepatic function within 14 days prior to registration defined as follows:

• Bilirubin < 2 mg/dl;
• Aspartate transaminase (AST) or alanine transaminase (ALT) < 3 x the upper limit of normal.

12. Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential;

13. Patients who are HIV positive but have no prior Acquired Immune Deficiency Syndrome (AIDS) -defining illness and have CD4 cells of at least 350/mm3 are eligible. HIV-positive patients must not have multi-drug resistant HIV infection or other concurrent AIDS-defining conditions. 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).

14. The patient must provide study-specific informed consent prior to study entry, including consent for mandatory submission of tissue for required, central p16 review.

15. Patients who speak English (or read one of the languages for which a translation is available (see Section 10.2) must consent to complete the mandatory dysphagia-related patient reported instrument (MDADI). If the patient cannot understand spoken English and reads only languages not available in the MDADI translations, the patient can still participate in the trial, as this has been factored into the trial statistics. For all other patients, the MDADI is mandatory as it is included in the primary endpoint to be studied.

Step 2: Randomization:

16. p16 positive by immunohistochemistry (defined as greater than 70% strong nuclear or nuclear and cytoplasmic staining of tumor cells), confirmed by central pathology review; (see Section 10.1 for details). Exclusion Criteria

Step 1: Registration:

1. Cancers considered to be from an oral cavity site (oral tongue, floor mouth, alveolar ridge, buccal or lip), or the nasopharynx, hypopharynx, or larynx, even if p16 positive, or histologies of adenosquamous, verrucous, or spindle cell carcinomas;

2. Carcinoma of the neck of unknown primary site origin (even if p16 positive);

3. Radiographically matted nodes, defined as 3 abutting nodes with loss of the intervening fat plane;

4. Supraclavicular nodes, defined as nodes visualized on the same axial imaging slice as the clavicle;

5. Definitive clinical or radiologic evidence of metastatic disease or adenopathy below the clavicles;

6. Gross total excision of both primary and nodal disease with curative intent; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease. In other words, to participate in this protocol, the patient must have clinically or radiographically evident gross disease for which disease response can be assessed.

7. Patients with simultaneous primary cancers or separate bilateral primary tumor sites are excluded with the exception of patients with bilateral tonsil cancers;

8. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1095 days (3 years) (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible);

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

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

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

• Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months;
• Transmural myocardial infarction within the last 6 months;
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;
• Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration;
• 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 other than those requested in Section 3.2.10.
• Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition with immune compromise greater than that noted in Inclusion Criterion 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.

12. Pregnancy; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.

13. Prior allergic reaction to cisplatin.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Oropharyngeal Neoplasms
• Squamous Cell Carcinoma of Head and Neck
• Stage III Oropharyngeal Squamous Cell Carcinoma
• Stage IVA Oropharyngeal Squamous Cell Carcinoma
• Stage IVB Oropharyngeal Squamous Cell Carcinoma
• Stage IVC Oropharyngeal Squamous Cell Carcinoma
• Tongue Carcinoma

Intervention

Drug:
• Cisplatin
40 mg/m2 IV (intravenously) weekly for 6 weeks

Radiation:
• IMRT 6 weeks
Intensity-modulated radiation therapy (IMRT), 30 fractions over 6 weeks, 5 fractions per week, 2 Gray per fraction to total dose of 60 Gy
• IMRT 5 weeks
Intensity-modulated radiation therapy (IMRT), 30 fractions over 5 weeks, 6 fractions per week, 2 Gray per fraction to total dose of 60 Gy

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	Kingston Health Sciences Centre	Kingston	Ontario
Canada	CHUM - Hopital Notre-Dame	Montreal	Quebec
Canada	Jewish General Hospital	Montreal	Quebec
Canada	McGill University Department of Oncology	Montreal	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Odette Cancer Centre- Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	University Health Network-Princess Margaret Hospital	Toronto	Ontario
Canada	BCCA-Vancouver Island Cancer Centre	Victoria	British Columbia
Canada	Windsor Regional Cancer Centre	Windsor	Ontario
Ireland	Saint Lukes Hospital	Dublin	Co Dublin
Saudi Arabia	King Faisal Specialist Hospital and Research Centre	Riyadh
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Mission Hospital Inc-Memorial Campus	Asheville	North Carolina
United States	Emory Saint Joseph's Hospital	Atlanta	Georgia
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Grady Health System	Atlanta	Georgia
United States	Piedmont Hospital	Atlanta	Georgia
United States	University of Colorado Hospital	Aurora	Colorado
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey
United States	UHHS-Chagrin Highlands Medical Center	Beachwood	Ohio
United States	UPMC-Heritage Valley Health System Beaver	Beaver	Pennsylvania
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
United States	Billings Clinic Cancer Center	Billings	Montana
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Boston Medical Center	Boston	Massachusetts
United States	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado
United States	Henry Ford Cancer Institute-Downriver	Brownstown	Michigan
United States	Mills-Peninsula Medical Center	Burlingame	California
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	Sutter Cancer Centers Radiation Oncology Services-Cameron Park	Cameron Park	California
United States	Geauga Hospital	Chardon	Ohio
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	John H Stroger Jr Hospital of Cook County	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	University of Cincinnati/Barrett Cancer Center	Cincinnati	Ohio
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Memorial Sloan Kettering Commack	Commack	New York
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Henry Ford Hospital	Detroit	Michigan
United States	Wentworth-Douglass Hospital	Dover	New Hampshire
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Mercy Cancer Center-Elyria	Elyria	Ohio
United States	Swedish Medical Center	Englewood	Colorado
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Parkview Hospital Randallia	Fort Wayne	Indiana
United States	Radiation Oncology Associates PC	Fort Wayne	Indiana
United States	University of Texas Medical Branch	Galveston	Texas
United States	Tacoma/Valley Radiation Oncology Centers-Gig Harbor	Gig Harbor	Washington
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	NorthShore University HealthSystem-Glenbrook Hospital	Glenview	Illinois
United States	CHI Health Saint Francis	Grand Island	Nebraska
United States	Mercy Health Saint Mary's	Grand Rapids	Michigan
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	North Colorado Medical Center	Greeley	Colorado
United States	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	Marin General Hospital	Greenbrae	California
United States	UPMC Cancer Centers - Arnold Palmer Pavilion	Greensburg	Pennsylvania
United States	Greenville Health System Cancer Institute-Eastside	Greenville	South Carolina
United States	Greenville Health System Cancer Institute-Faris	Greenville	South Carolina
United States	Greenville Health System Cancer Institute-Greer	Greer	South Carolina
United States	Legacy Mount Hood Medical Center	Gresham	Oregon
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	NorthShore University HealthSystem-Highland Park Hospital	Highland Park	Illinois
United States	Memorial Regional Hospital/Joe DiMaggio Children's Hospital	Hollywood	Florida
United States	Queen's Medical Center	Honolulu	Hawaii
United States	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii
United States	M D Anderson Cancer Center	Houston	Texas
United States	MD Anderson in Katy	Houston	Texas
United States	Cleveland Clinic Cancer Center Independence	Independence	Ohio
United States	UW Cancer Center Johnson Creek	Johnson Creek	Wisconsin
United States	UPMC-Johnstown/John P. Murtha Regional Cancer Center	Johnstown	Pennsylvania
United States	North Kansas City Hospital	Kansas City	Missouri
United States	The University of Kansas Cancer Center-North	Kansas City	Missouri
United States	The University of Kansas Cancer Center-South	Kansas City	Missouri
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	Vidant Oncology-Kinston	Kinston	North Carolina
United States	Tennessee Cancer Specialists-Dowell Springs	Knoxville	Tennessee
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	UTMB Cancer Center at Victory Lakes	League City	Texas
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	The University of Kansas Cancer Center-Lee's Summit	Lee's Summit	Missouri
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	Saint Mary Mercy Hospital	Livonia	Michigan
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Jewish Hospital Medical Center Northeast	Louisville	Kentucky
United States	The James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	UPMC Cancer Center at UPMC McKeesport	McKeesport	Pennsylvania
United States	Community Memorial Hospital	Menomonee Falls	Wisconsin
United States	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio
United States	Miami Cancer Institute	Miami	Florida
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	UH Seidman Cancer Center at Southwest General Hospital	Middleburg Heights	Ohio
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Community Medical Hospital	Missoula	Montana
United States	Memorial Medical Center	Modesto	California
United States	UPMC-Coraopolis/Heritage Valley Radiation Oncology	Moon	Pennsylvania
United States	Virtua Memorial	Mount Holly	New Jersey
United States	Intermountain Medical Center	Murray	Utah
United States	Mercy Health Mercy Campus	Muskegon	Michigan
United States	MD Anderson League City	Nassau Bay	Texas
United States	Yale University	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Kaiser Permanente Oakland-Broadway	Oakland	California
United States	McKay-Dee Hospital Center	Ogden	Utah
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Olathe Medical Center	Olathe	Kansas
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Lakeside Hospital	Omaha	Nebraska
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas
United States	Palo Alto Medical Foundation Health Care	Palo Alto	California
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	Parker Adventist Hospital	Parker	Colorado
United States	University Hospitals Parma Medical Center	Parma	Ohio
United States	Memorial Hospital West	Pembroke Pines	Florida
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	UPMC-Passavant Hospital	Pittsburgh	Pennsylvania
United States	UPMC-Saint Margaret	Pittsburgh	Pennsylvania
United States	UPMC-Shadyside Hospital	Pittsburgh	Pennsylvania
United States	Ascension All Saints Hospital	Racine	Wisconsin
United States	Kaiser Permanente-Rancho Cordova Cancer Center	Rancho Cordova	California
United States	Beebe Health Campus	Rehoboth Beach	Delaware
United States	Renown Regional Medical Center	Reno	Nevada
United States	Saint Mary's Regional Medical Center	Reno	Nevada
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Rohnert Park Cancer Center	Rohnert Park	California
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California
United States	The Permanente Medical Group-Roseville Radiation Oncology	Roseville	California
United States	South Sacramento Cancer Center	Sacramento	California
United States	Sutter Medical Center Sacramento	Sacramento	California
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Saint Helena Hospital	Saint Helena	California
United States	Norris Cotton Cancer Center-North	Saint Johnsbury	Vermont
United States	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Utah Cancer Specialists-Salt Lake City	Salt Lake City	Utah
United States	Naval Medical Center -San Diego	San Diego	California
United States	UCSF Medical Center-Mount Zion	San Francisco	California
United States	Stanford Cancer Center South Bay	San Jose	California
United States	North Coast Cancer Care	Sandusky	Ohio
United States	UH Seidman Cancer Center at Firelands Regional Medical Center	Sandusky	Ohio
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Greenville Health System Cancer Institute-Seneca	Seneca	South Carolina
United States	UPMC Cancer Center at UPMC Northwest	Seneca	Pennsylvania
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	HSHS Saint Nicholas Hospital	Sheboygan	Wisconsin
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	City of Hope South Pasadena	South Pasadena	California
United States	Kaiser Permanente Cancer Treatment Center	South San Francisco	California
United States	Greenville Health System Cancer Institute-Spartanburg	Spartanburg	South Carolina
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Cleveland Clinic Cancer Center Strongsville	Strongsville	Ohio
United States	Palo Alto Medical Foundation-Sunnyvale	Sunnyvale	California
United States	NHRMC Radiation Oncology - Supply	Supply	North Carolina
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	MultiCare Tacoma General Hospital	Tacoma	Washington
United States	Tacoma/Valley Radiation Oncology Centers-Jackson Hall	Tacoma	Washington
United States	Tacoma/Valley Radiation Oncology Centers-Saint Joe's	Tacoma	Washington
United States	Moffitt Cancer Center	Tampa	Florida
United States	MD Anderson in The Woodlands	The Woodlands	Texas
United States	Gene Upshaw Memorial Tahoe Forest Cancer Center	Truckee	California
United States	Banner University Medical Center - Tucson	Tucson	Arizona
United States	Memorial Sloan Kettering Nassau	Uniondale	New York
United States	UPMC Uniontown Hospital Radiation Oncology	Uniontown	Pennsylvania
United States	Legacy Salmon Creek Hospital	Vancouver	Washington
United States	Virtua Voorhees	Voorhees	New Jersey
United States	John Muir Medical Center-Walnut Creek	Walnut Creek	California
United States	UPMC Washington Hospital Radiation Oncology	Washington	Pennsylvania
United States	The Alyce and Elmore Kraemer Cancer Care Center	West Bend	Wisconsin
United States	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan
United States	University Pointe	West Chester	Ohio
United States	Reading Hospital	West Reading	Pennsylvania
United States	UHHS-Westlake Medical Center	Westlake	Ohio
United States	Cleveland Clinic-Weston	Weston	Florida
United States	Dickstein Cancer Treatment Center	White Plains	New York
United States	Ascension Via Christi Hospitals Wichita	Wichita	Kansas
United States	NHRMC Radiation Oncology - 16th Street	Wilmington	North Carolina
United States	Aspirus UW Cancer Center	Wisconsin Rapids	Wisconsin
United States	Cleveland Clinic Wooster Family Health and Surgery Center	Wooster	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
NRG Oncology	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada,  Ireland,  Saudi Arabia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Alive Without Progression at Two Years (Progression-free Survival)	Progression is defined as local, regional, or distant disease progression or death due to any cause. Percentage is estimated using the binomial distribution.	From randomization to 2 years
Secondary	Percentage of Participants With Local-regional Failure	Local-regional failure is 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 are considered competing risks. Local-regional failure time is defined as time from randomization to the date of first progression/death or last known follow-up (censored). Rates are estimated by the cumulative incidence method.	From randomization to 2 years
Secondary	Percentage of Participants With Distant Metastasis	Distant metastasis is defined as distant progression. Local-regional failure and death due to any cause are 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.	From randomization to 2 years
Secondary	Percentage of Participants Alive	Overall survival time is defined as time from randomization to the date of death or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method.	from randomization to 2 years
Secondary	Percentage of Participants With Grade 3+ Adverse Events	Adverse events 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.	End of radiation therapy (RT) (approximately 6 weeks for Arm 1 and 5 weeks for Arm 2), then 1 month, 6 months, 1 year, and two years after end of RT
Secondary	Mean One-year Total MD Anderson Dysphagia Inventory (MDADI) Score (Patient-reported Swallowing Outcome)	The MDADI is a 20-item tool with each item scored as Strongly agree; Agree; No opinion; Disagree; or Strongly disagree. There is 1 global item (G1), 6 emotional subscale items (E2-E7), 5 functional subscale items (F1-F5), and 8 physical subscale items (P1-P8). For all items except E7 and F2, Strongly agree corresponds to a score of 1, Agree 2, No opinion 3, Disagree 4, and Strongly disagree 5. For E7 and F2, the scores are reversed; these 2 items are rescored to match the others before calculating summary scores. The composite (total) score is the mean of the 19 items (other than G1) X 20. Composite scores range from 20 to 100 with higher scores indicating less dysphagia.	One year post-RT. Radiation therapy (RT) ends at approximately 6 weeks for Arm 1 and 5 weeks for Arm 2
Secondary	Negative Predictive Value (NPV) of Post-treatment FDG-PET/CT Scan [Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)/Computed Tomography (CT)] for Progression-free Survival and Local-regional Control at Two Years	NPV is the percentage of participants alive and failure-free at 2 years among those with a negative post-treatment scan, as evaluated by central review. Negative scan determined as follows: primary site, right neck, left neck evaluated using a 5-point ordinal scale: 1-Definite complete metabolic response (CMR), 2-Likely CMR, 3-Likely inflammatory, 4-Likely residual metabolic disease (RMD), and 5-Definite RMD. 'Negative'= 1 or 2, 'Indeterminate'=3, 'Positive' = 4 or 5. 'Negative' for all three evaluation sites = overall score of 'Negative.' Progression (failure) is defined as local, regional, or distant disease progression (PR) or any death. Local-regional progression (failure) is defined as local or regional PR, salvage surgery of the primary tumor with tumor present/unknown, salvage neck dissection with tumor present/unknown > 20 weeks post RT, death due to study cancer or unknown causes without documented PR. The protocol specified that both arms would be combined for analysis.	3 months (scan) and two years after the end of RT (approximately 6 weeks for Arm 1 and 5 weeks for Arm 2)
Secondary	Human Papillomavirus (HPV) Deoxyribonucleic Acid (DNA) Detection Rate	With a two-sided type error rate of 5% and based on chi-squared test for proportions, there is a greater than 99% power to detect HPV DNA detection rate of 65% and 95% between the 2 groups (n=140 in each arm). The rate of detection for each group will be summarized based on binomial distributions and a 95% confidence intervals (CI) will be provided.	Baseline to up to 2 weeks after the completion of treatment
Secondary	HPV DNA Rate Decline	With a two-sided type error rate of 5% and based on paired t test for means, there is 99% power to detect HPV DNA rate decline of 0.375 (effect size) within each arm (n=140). The HPV DNA rate for each group will be summarized using means and standard deviations.	Baseline to up to 2 weeks after the completion of treatment
Secondary	HPV DNA Copy Number	Correlation between HPV DNA copy number and the nodal metabolic volume will be calculated using Spearman's correlation coefficient and R2, and the corresponding 95% CI will be provided.	Baseline to up to 2 weeks after the completion of treatment
Secondary	Variance for HPV DNA	Univariable and multivariable cause specific analysis will be performed using the Cox proportional hazards model for rate of relapse.	Baseline to up to 2 weeks after the completion of treatment